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On 2017 May 24, Jordan Anaya commented:
I think readers of this article will be interested in a comment I posted at F1000Research, which reads:
I would like to clarify and/or raise some issues with this article and accompanying comments.
One: Reviewers Prachee Avasthi and Cynthia Wolberger both emphasized the importance of being able to sort by date, and in response the article was edited to say: "Currently, the search.bioPreprint default search results are ordered by relevance without any option to re-sort by date. The authors are aware of the pressing need for this added feature and if possible will incorporate it into the next version of the search tool."
However, it has been nearly a year and this feature has not been added.
Two: The article states: "Until the creation of search.bioPreprint there has been no simple and efficient way to identify biomedical research published in a preprint format..."
This is simply not true as Google Scholar indexes preprints. This was pointed out by Prachee Avasthi and in response the authors edited the text to include an incorrect method for finding preprints with Google Scholar. In a previous comment I pointed out how to correctly search for preprints with Google Scholar, and it appears the authors read the comment given they utilize the method at this page on their site: http://www.hsls.pitt.edu/gspreprints
Three: In his comment the author states: "We want to stress that the 'Sort by date' feature offered by Google Scholar (GS) is abysmal. It drastically drops the number of retrieved articles compared to the default search results."
This feature of Google Scholar is indeed limited, as it restricts the results to articles which were published in the past year. However, if the goal is to find recent preprints then this limitation shouldn't be a problem and I don't know that I would classify the feature as "abysmal".
Four: The article states: "As new preprint servers are introduced, search.bioPreprint will incorporate them and continue to provide a simple solution for finding preprint articles."
New preprint servers have been introduced, such as preprints.org and Wellcome Open Research, but search.biopreprint has not incorporated them.
Five: Prachee Avasthi pointed out that the search.biopreprint search engine cannot find this F1000Research article about search.biopreprint. It only finds the bioRxiv version. In response the author stated: "The Health Sciences Library System’s quality check team has investigated this issue and is working on a solution. We anticipate a quick fix of this problem."
This problem has not been fixed.
Competing Interests: I made and operate http://www.prepubmed.org/, which is another tool for searching for preprints.
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On 2016 Jun 24, Ole Jakob Storebø commented:
We think that the clinicians prescribing methylphenidate for ADHD and others have been insufficiently critical of the literature for decades, trusting that the quality of methylphenidate research was reasonable. In accordance, Shaw in an editorial accompanying our JAMA article Storebø OJ, 2016 stated that the Epstein et al. review on methylphenidate for adults with ADHD was an example of good assessments of quality Shaw P, 2016. It seems Shaw erred, as the Epstein et al. review has now been withdrawn from The Cochrane Library due methodological flaws Epstein T, 2016.
Banaschewski et al. suggest that we included five trials in our analyses that should have been excluded. We think they are wrong. They highlight four trials which they cite as having used “active controls” whereas these are actually co-interventions, used in both the methylphenidate and the control group. Such trials are includable in accordance with our protocol Storebø OJ, 2015. Moreover, excluding these trials from our review would only have produced negligible changes in our results. Furthermore, the trial including children aged 3 to 6 years ought also to have be included in accordance with our protocol. Excluding all five trials would not have changed our conclusions at all. We concluded that methylphenidate might improve teacher reported symptoms of ADHD. However, the very low quality of the evidence, the magnitude of that effect size is uncertain. A change in the effect size of 0.12 points on the standardised mean difference of this outcome would not change anything.
In a subgroup analysis comparing parallel trials and crossover trials, we did not find a significant difference either. However, we noted considerable heterogeneity between the two groups of trials. It is not recommended to pool cross-over trials which only have “end-of-trial data” with parallel group trials (http://handbook.cochrane.org/) and had we done so we would have would risked introducing a “unit-of-analysis error” as we only had “end-of-trial data” from these cross-over trials.
We agree that the variability of the minimal relevant difference is important which is why we reported the 95% confidence interval of the transformed mean value in our review Storebø OJ, 2015. Banaschewski et al. also suggest that we have overlooked information in the Coghill 2007 trial and thereby wrongly assessed this as a trial with “high risk of bias”. We stated in our protocol that we would consider trials with one or more unclear or high risk of bias domain as trials with high risk of bias Storebø OJ, 2015.
We did not overlook information from the Coghill 2007 trial but twice emailed the authors for additional information. They did not respond. The information required is not available in the published study. We presented the risk of bias assessments for the various domains of all 185 included trials. It is correct that we assessed seven cross-over trials as low risk of bias and not six as reported. Thank you for spotting this error. The seventh trial is reported, however, in our table in which the risk of bias assessments for all the domains is shown. All trials, irrespective of vested interest bias, were regarded as having a high risk of bias due to broken outcome assessor blinding given the easily recognisable, well-known adverse effects of methylphenidate. When adding this seventh cross-over trial to the subgroup analysis on the outcome “teacher-rated ADHD symptoms – cross-over trials”, we now find significant differences between the trials with “high” compared to “low” risk of bias (standardised mean difference (SMD) -0.96 [95% confidence interval -1.09 to -0.82] compared to -0.64 [-0.91 to -0.38]. Test for subgroup difference: Chi² = 4.27, df = 1 (P = 0.04), I² = 76.6%).
Banaschewski et al. focus only on our assessment of risk of bias and do not mention the core instrument for assessing quality of meta-analyses namely the Grades of Recommendation Assessment Development and Evaluation (GRADE) approach Andrews J, 2013. Our assessment of the evidence as “very low quality” is not only based on the assessment of risk of bias, but also on other factors such as heterogeneity, imprecision, and indirectness of the evidence. This is clearly reported in our review.
We downgraded the quality of the included trials in the meta-analysis for imprecision and for moderate heterogeneity. The durations of included trials were short, with an average of 75 days. Most patients receive methylphenidate treatment for substantially longer periods and the beneficial effects may diminish over time Jensen PS, 2007 Molina BS, 2009. The short trial duration could suggest the need for further downgrading for “indirectness” according to GRADE Andrews J, 2013. We did not downgrade for this, but we could have. This further underlines that the evidence for the benefits and harms for the use of methylphenidate for children and adolescents with ADHD is of very low quality.
We have assessed 71 trials as having high risk of bias in the “vested interest” domain as they were funded by the industry and/or the authors were affiliated with the industry.
It is not incorrect for us to state that none of the trials funded by the pharmaceutical industry showed a low risk of bias in all other areas as we considered all the trials as high risk of bias on the domain of blinding. This is clearly reported in our review.
We have now conducted the requested subgroup analysis comparing those trials with high compared to low risk of vested interest bias on the teacher-rated ADHD symptoms outcome. The effect of methylphenidate in the 14 trials with high risk of vested interest bias was SMD -0.86 [-0.99 to -0.72] compared to SMD -0.50 [-0.69 to -0.31] in the 5 trials with low risk of vested interest bias. Test for subgroup differences is Chi² = 8.67, df = 1, P = 0.003. So even in this small sample we find a significant difference.
We recommend Banaschewski et al. to read the essay by John P Ioannidis about vested interests Ioannidis JP, 2016.
It is important to stress that the results of our review would have been the same had we disregarded the issue of vested interest.
Had there been inconsistencies regarding one domain of bias in a few trials they would not change the fact that these trials are to be considered as trials at high risk of bias. For example, in two trials, Konrad 2004 and Konrad 2005, there is inconsistency in how our author teams assessed the randomisation process. However, both trials have several other domains at “unclear risk of bias” or “high risk of bias”. In the Ullman 2006 trial, three domains are assessed as “unclear risk of bias”. In Wallace 1994, five domains are assessed as being of “unclear risk of bias” and one as “high risk of bias”. In Wallander 1987, five domains are assessed as “unclear risk of bias”. Even if there was inconsistency between one or two items, these trials are high risk of bias trials. There may well be small differences in our judgements, but that does not change the fact that the trials included are, in general, trials at high risks of bias Storebø OJ, 2015. It is important to understand that we followed the Cochrane guidelines in every aspect of our review.
Conclusions
We have demonstrated that the trial selection in our review was not flawed and was undertaken with sufficient scientific justification The effect sizes are not too small. We have followed a sound methodology for assessing risk of bias and our conclusion is not misleading. We are concerned about the state of the academic literature and at the financial and academic waste that has occurred, given that more than 250 reviews and 3000 single works have been published on psychostimulants for ADHD treatment. Despite this, there is still no sound evidence regarding the benefits and harms of methylphenidate.
Ole Jakob Storebø, Morris Zwi, and Christian Gluud.
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On 2017 Jul 03, P Jesper Sjöström commented:
Thanks for your interest in our work. I would like to make the following points:
We did not actually say 'no connections in mature cortex' -- that quote is certainly not lifted from Mizusaki et al Nat Neurosci 2016. We said "In fact, it was recently reported that, surprisingly, pyramidal cells in visual cortex of mature animals do not seem to interconnect at all, neither bidirectionally nor unidirectionally12," where 12 refers to Jiang et al. We thus say that Jiang et al report that PCs do not seem to interconnect, we do not say that there are no PC-PC connections in mature cortex. What Jiang et al state and what our opinion about that statement is, those are different things.
The intention of that passage in Mizusaki et al is to point out that Brunel is using my data from Song et al as a gold standard, but this may or may not be appropriate, since my connectivity data was acquired from a developmental snapshot in time (just after eye opening, typically postnatal day 14-16), whereas Brunel is in fact focussing on the functioning of the mature brain, when circuits are wired up. Our intention was thus to acknowledge that my own data need not be the ground truth, and this has important implications for the validity of the Brunel study. The Tolias study provides an alternative view: "the most compelling and consistent difference across experiments is the age of the animals tested, suggesting that mature cortical circuits are not identical to developing circuits." Such a developmental difference would important in the context of the Brunel study. Again, this is not necessarily my opinion, but as scientists, we have to acknowledge this possibility.
In the Tolias study, they report in Fig S14 that they found precisely zero L5 PC-PC connections even after 150 attempts, which is in stark contrast to my connectivity data presented in Song et al. Indeed, if you do a Chi-squared test for 931/8050 versus 0/150, you will find that this is a highly significant difference. We can debate the accuracy of the Tolias measurement (like they do in Barth et al Science 2016 353:1108, as you point out), but if we do so, we should also debate the accuracy of my measurements in juveniles, as presented in Song et al. While it is true that my data in Song et al is more in line with e.g. Thomson et al Cereb Cortex 2002 than with Jiang et al, the key point in the context of Brunel's theoretical study is that the ground truth is not necessarily well established.
In summary, I certainly believe in my own connectivity data set, and I think Brunel's study provides a very compelling theoretical framework for explaining such connectivity patterns, but I feel obliged to point out a few possible caveats associated with my connectivity data set. Jiang et al provide one such key caveat. I hope this clarifies somewhat.
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On 2016 Mar 24, Jeromy Anglim commented:
Thanks for posting a comment. I just wanted to add a few thoughts on your points.
Relationship between type D and outcomes were not moderated by illness group. For us, this was the important conclusion that we want researchers to think about. There is a lot of research done examining Type D in specific illness groups. To some extent implicit in such research is the idea that the effect of Type D might vary based on illness type. While this may be true, this study presents some evidence that at least for the illness groups and variables studied, this is not the case.
The effect of negative affect on social support and the effect of social inhibition on health behaviours failed to reach statistical significance. I would not say that it failed. This is actually an important finding that supports the idea that the subscales of Type D provide different correlates (i.e., negative affectivity is related more to affective processes, and social inhibition is related more to social processes). Presumably, this is as we would expect. Although if you wanted to be critical, there is the idea that NA is merely neuroticism, and SI is a mix of neuroticism and introversion (see Horwood, Anglim, Tooley, 2015). Whether that is a problem probably depends on how primary you view Big 5 personality.
Limitations: I think we note the limitations you mention in the limitations section. That said, those limitations only relate to certain points of the paper. For me personally, I think that the paper has two fairly important implications for researchers working with Type D personality. The first relates to the general lack of variation in effects by group as discussed above. Second, we did a comparative regression analysis comparing a range of different scoring systems for Type D personality. The results suggested that binary Type D is a poor predictor, and there was limited evidence for NA by SI interactions effects. Rather entering NA and SI as two separate predictors generally resulted in the best prediction of outcomes. This goes agains the implicit claims of Type D that there is an interactive effect and that cut-offs are appropriate for Type D. Importantly, all these analyses also speak to the novelty of the Type D construct and the rationale for choosing the two particular subscales for inclusion.
Thus, for me, the paper provides a nuanced and critical assessment of the predictive validity of Type D personality. In particular, I'd encourage other researchers working with Type D personality (and some are doing this already) to run the comparative regression analyses in their samples.
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On 2016 Jun 21, Evelina Tutucci commented:
We have also recently discussed Nelles et al. Nelles DA, 2016. Since we are interested in developing new techniques for studying gene expression and mRNA localization at the single molecule level, a potential tag-less system to detect mRNAs in fixed and live cells would be a further advance. As pointed out by the Duke RNA Biology journal club we think that Nelles et al. represents an attempt to apply the Cas9 System to detect endogenous mRNA molecules. Unfortunately, no evidence is presented to demonstrate that this system is ready to be used to study gene expression at the single molecule level, as the MS2-MCP system allows. The RNA letter by Garcia and Parker Garcia JF, 2015 showed that in S. cerevisiae the binding of the MS2 coat protein to the MS2-loops diminished tagged mRNA degradation by the cytoplasmic exonuclease Xrn1. However, these observations were not extended to higher eukaryotes. Previous work from our lab described the generation of the beta-actin-MS2 mouse, whereby all the endogenous beta-actin mRNAs were tagged with 24 MS2 loops in the 3’UTR (Lionnet T, 2011, Park HY, 2014). This mouse is viable and no phenotypic defects are observed. In addition, control experiments were performed to show that the co-expression of the MS2 coat protein in the beta-actin-MS2 mouse allowed correct mRNA degradation and expression (Supplementary figure 1b, Lionnet T. et al 2011). Furthermore, multi-color FISH (Supplementary figure 6, Lionnet T. et al 2011) showed substantial co-localization between the ORF FISH probes and MS2 FISH probes, demonstrating the validity of this model. We think that the observations by Garcia and Parker are restricted to yeast because of the short half-life of their mRNAs, wherein the degradation of the MS2 becomes rate-limiting. Based on our extensive use of the MS2-MCP system, we think that higher eukaryotes may have more time to degrade the high affinity complexes formed between MS2-MCP, providing validation for this system to study multiple aspects of gene expression. In conclusion, we think that the MS2-MCP system remains to date the best method to follow mRNAs at the single molecule level in living cells. For the use of the MS2-MCP system in S. cerevisiae we have taken the necessary steps to improve it for the study of rapidly degrading mRNAs and are preparing this work for publication.<br> Evelina Tutucci and Maria Vera, Singerlab
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On 2016 May 17, Duke RNA Biology Journal Club commented:
These comments were generated from a journal club discussion:
We were excited to read and discuss this paper as many of us have questions pertaining to mRNA localization. This technique theoretically allows for imaging of mRNAs without genetic manipulation meaning mRNAs at native expression levels can be tracked in live cells. However, as with many cutting-edge papers, more work is needed before this will become commonplace in the lab.
Most current methods to track mRNAs in live cells involve aptamer based methods which require genetic manipulation of mRNA PMCID: PMC2902723. Additionally, the most commonly used aptamer system, the MS2-MCP system, has become controversial in light of recent findings that the MS2 coat protein stabilizes the aptamer bearing constructs Garcia JF, 2015. In this paper, Fig 1F and 1G replicated these findings and also reassured us that the RCas9 technique would not have the same downfall. While this is certainly a good thing, we were unconvinced this technique was better than FISH (Fig 2), other than having the potential for live cell imaging.
Unfortunately, we found the live cell imaging, which was limited to Fig 3B, to be disappointing. First, we observed that unless an mRNA is strictly localized, as in stress granules, live imaging shows a diffuse mass within the cytosol. Second, imaging was performed with ACTB mRNA which is highly abundant. We don’t think live cell imaging would work as well for low abundance mRNAs due to high background signal. Finally, while specialized imaging software can detect the pile-ups of mRNA in localized foci, we are concerned that tracking individual mRNA may prove a hurdle. Cell models for mRNA localization are large cells such as fibroblasts and neurons, we would be interested to see the ability of this system within these cell types.
One major flaw with this system is the lack of ability to monitor nuclear localized RNA such as lncRNA or splicing machinery. Since since the RCas9 and sgRNA have to first be produced in the nucleus, the majority of the signal in all the figures came from the nucleus. There is a split-GFP-PUM-HD system that has been used to successfully track mRNA in mitochondria Ozawa T, 2007. Perhaps a similar concept could be used with the Cas9 system. This would prove an advantage to the Pumilio system since only the sgRNA needs to be modified instead of the entire protein.
Overall, this is a great start towards a new, tagless, method of mRNA tracking. We look forward to future developments and improvements of this exciting technique.
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On 2016 Mar 25, Michael R Blatt commented:
Dear Boris,
There’s nothing grand in these statements nor are they exempt from a cost-benefit analysis. It just happens that my measures of cost and benefit are (obviously) different from yours. Of course, it may be that we can still find common ground, and I would hope this is the case.
As to your question “Is it a good thing to alert readers … to possible problems?”, clearly the answer is yes. I have said so repeatedly in my editorials and here on PubMed Commons. However, in my opinion, this needs to be done in a way that does not open the door to abuse, misrepresentation, sock-puppetry, and other antisocial or ethically unsound behaviours. I don’t think this is a particularly difficult concept, even if its solution is more complex in practice.
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On 2016 Mar 22, Michael R Blatt commented:
Dear Boris,
I really do not think that we are so far apart in our views. We both are dismayed by some of what we see in scientific publishing and communication today, and we both want the same for the scientific community as a whole. Where we differ is only in some details of the means to this end.
The point you raise is of measures, ‘averages’, and quantity, rather than of principle. I do not doubt that there are many comments on PubPeer that are thoughtful and constructive. I certainly never suggested that all comments on PubPeer “abuse the system” (nor did I ever suggest coersion, so let us not confuse the issue here). The point on which we differ is whether the quantitative argument for anonymity that you pose outweighs the foundational arguments I have set out against it. I think not.
You raise the analogy to the utility of cars and whether these should be banned. Of course analogies are poor vehicles (pun intended) for ideas, but let’s follow it for a moment. It would be virtually impossible to ban anonymous commenting from social media, just as it is impossible to ban reckless driving (I recall you had this discussion with Philip Moriarty previously). However, this is not to say that either should be actively encouraged. There are norms for interpersonal interaction that we generally follow and that protect civil society (e.g. accountability), just as there are rules of the road and legal requirements (e.g. the need for a driving license) that are there to protect us when we are on the road.
I think it is always important to look for other ways to a solution. Answers sometimes come from taking an entirely different perspective rather than looking for the common denominator. So, to follow your analogy one step further, rather than banning cars (and anonymous commenting), would it not be better to make them less attractive as a whole while making the use of public transport (and of open, accountable commenting) more attractive? Are we not both in a position to influence the process of PPPR?
I alluded, at the end of my March 2016 editorial, to what I hope will be an approach to such a ‘third solution.’ It comes straight out of discussions with Leonid Schneider who, I think you will recall, was originally one of my fiercest critics last October. I am convinced this alternative is worth a try and, at this point, have a number of my opposite numbers from other publishers on board. You may be convinced as well in due course. Again, I hope that I will have much more to say on this matter later this year.
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On 2016 Mar 20, Linda Z Holland commented:
In my review, I did not intend to criticize the ability of ascidian development to say something about the role of gene subnetworks in developing systems in vivo—it is a fruitful approach worthy of vigorous pursuit. Ascidians are highly tractable for experimental embryology and have scaled-down genomes and morphologies (at least with respect to vertebrates). As a result, noteworthy progress is being made in elucidating the gene networks involved in ascidian notochord development (José-Edwards et al. 2013, Development 140: 2422-2433) and heart development (Kaplan et al. (2015. Cur Opin Gen Dev 32: 119-128). It is currently a useful working hypothesis to make close comparisons between gene subnetworks in ascidians and other animals (Ferrier 2011. BMC Biol 9: 3). At present, however, the genotype-to-phenotype relationship is an unsolved problem in the context of a single species, and to consider the problem across major groups of animals is to venture deep into terra incognita. Much more work on the development in the broadest range of major animal taxa will be required to determine how (or even if) genotypes can predict phenotypes in vivo in embryos and later life stages. Studies of this complex subject, which are likely to require a combination of experimental data and computational biology (Karr et al, 2012. Cell 150: 389-401) are still in their infancy. That said, when I consider the developmental biology of animals in general, I think it is very likely that the highly determinate embryogenesis and genomic simplifications of ascidians are evolutionarily derived states. It is possible that this ancestor may have been more vertebrate-like than tunicate-like. For example, it might have had definitive neural crest, and the situation in modern ascidian larvae, which apparently have part of the gene network for migratory neural crest, may represent a simplification from a more complex ancestor. In the absence of fossils that could represent the common ancestor of tunicates and vertebrates, we cannot reconstruct a reasonable facsimile of this ancestor. Given that tunicates are probably derived, it is not very likely that any amount of research on modern chordates will solve this problem.
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On 2016 Feb 04, Ivan Shatsky commented:
It is a fruitful idea to use a high- throughput assay to fish out sequences that regulate translation initiation. I like this idea. It may result in very useful information provided that the experimental protocol is correctly designed to reach the goal of a study. However, while reading the text of the article I had an impression that the authors did not make a clear difference between the terms “IRES-driven translation” and “cap-independent” translation. In fact, cap-independent mechanisms may be of two kinds: a mechanism that absolutely requires the free 5’ end of mRNA (see e.g. Terenin et al. 2013. Nucleic Acids Res. 41(3):1807-16 and references therein and Meyer et al. 2015. Cell 163(4): 999-1010 ) and that which is based on internal initiation. Only in the latter case a 5’ UTR starts penetrating the mRNA binding channel of ribosomes with an internal segment of the mRNA rather than with a free 5’ end. Consequently, the experimental design should be distinct for these two modes of cap-independent translation. The method of bicistronic constructs used by the authors is suitable exclusively to identify IRES-elements. However, this approach is sufficiently reliable when it is employed in the format of bicistronic RNAs transfected into cultured cells. It is repeatedly shown that the initial format of bicistronic DNAs is extremely prone to almost unavoidable artifacts (for literature, see ref. 48 in the paper and the review by Jackson, R.J. The current status of vertebrate cellular mRNA IRESs. Cold Spring Harb Perspect Biol, 2013; 5). The control tests to reveal these artifacts which are still used (unfortunately!) by many researchers are not sensitive enough to detect formation of few percents of monocistronic mRNAs. (To this end, one should perform precise and laborious experiments which are not realistic in the case of high-throughput assays.). The capping of these aberrant mono- mRNAs can produce a dramatic stimulation of their translation activity (20-100 fold, depending on cell line). Therefore, even few percents of capped mono-mRNAs may result in a high activity of the reporter as compared to an almost zero activity of empty vector (see Andreev et al. 2009. Nucleic Acids Res.37(18):6135-47 and references therein). Real-time PCR assessment of mRNA integrity (Fig. S4) is an easy way to miss these few percents of aberrant transcripts. The other concern is genome-wide cDNA/gDNA estimation. The ratio for e.g. “c-myc IRES” is 2<sup>-1.6</sup> which is roughly 1/3 (Fig. S3). Does this mean that 2/3 of c-myc transcripts are monocistronic rather than bicistronic? I had a general impression that the authors were not aware of serious pitfalls inherent to the method of bicistronic DNA constructs and simply adapted this method to their high throughput assay. At least, I did not find citations of papers that discussed this important point.
The data in section Supplementary materials (Figs. S5 and S6) give us expressive and compelling evidence of such kind of artifacts: indeed, some 174 nt long fragments from the EMCV IRES possessed an IRES activity. Moreover, one of them with GNRA motif had the activity similar to that for the whole EMCV IRES (!?). This result is in an absolute contradiction with our current knowledge on this picornaviral IRES, one the best studied IRES elements! Parts of the EMCV IRES are known to have no activity at all! Thus, the most plausible explanation is that the EMCV fragments harbor cryptic splice sites. The same is true for other picornavirus IRESs examined in these assays. The HCV IRES tested by the authors in the same experiments worked only as a whole structure (Fig.S6B), in a full agreement with data of literature. However, this result may not encourage us as it just means that the data obtained in this study may be a mixture of true regulatory sequences with artifacts. We should keep in mind that the existence of viral IRES-elements is a firmly established fact. They have a complex and highly specific organization with well defined boundaries and THEY ARE ONLY ACTIVE AS INTEGRAL STRUCTURES. The minimal size of IRESs from RNAs of animal viruses is >300 nts. Their shortening inactivates them and therefore, they cannot be studied with cDNA fragments of 200 nt long or less. Thus, I think it was a mistake to mix viral IRESs with cellular mRNA sequences. As to cellular IRESs, none of them has been characterized and hence we do not know what they are and whether they even exist. For none of them has been shown that they do not need a free 5’ end of mRNA to locate the initiation codon. Some of them have already been disproved (c-Myc, eIF4G, Apaf-1 etc.). By the way, I do not know any commercial vector that employs a cellular IRES. Thus, I think that we should first find adequate tools to identify cellular IRESs, characterize several of them, and only afterwards we may proceed to transcriptome-wide searching for cellular IRESs.
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On 2016 Jun 24, Lydia Maniatis commented:
The authors do two things in this study:
First, they point out that past studies on “constancy” have been hopelessly confounded due a. to condition-sensitivity of and ambiguity in what is actually percieved and b. questions that are confusing to observers because they are vague, ambiguous, unintelligible or unanswerable on the basis of the percept, thus forcing respondents to try to guess at the right answer. As a result, the designers of these studies have generated often incoherent data and proferred vague speculations as to the reasons for the randomness of the results.
Second, as though teaching (what to avoid) by example, they produce yet another study embodying all of the problems they describe. Using arbitrary sets of stimuli, they ask an arbitrary set of questions of varying clarity/answerability-on-the-basis-of-the-percept, and generate the typically heterogeneous, highly variable set of outcomes, accompanied by the usual vague and non-committal discussion. (The conditions and questions are arbitrary in the sense that we could easily produce a very different set of outcomes by (especially) changing the colors of the stimuli or (less importantly) changing the questions asked.) Thus, the only possible value of these experiments would be to show the condition-dependence of the outcomes. But this was an already established fact, and it is, furthermore, a fact that any experimenter in any field should be aware of. It's the reason that planning an experiment requires careful, theory-guided control of conditions.
The authors make no attempt to hide the fact that some of the questions they ask participants cannot be anwered by referring to the percept. For example,, they are asked about some physical characteristic of the simulus, which, of course, is inaccessible to either the human visual system and unavailable in the conscious percept. In these cases, we are not studying perception of the color of surfaces, but a different kind of problem-solving. The authors refer to answers “based on reasoning.” If we're interested in studying color perception, then the simple answer would be not to use this type of question. The authors seem to agree: “Although we believe that the question of how subjects can reason from their percepts is interesting in its own right, we think it is a different question from how objects appear. Our view is that instructional effects are telling us about the former, and that to get at the latter neutral instructions are the most likely to succeed...In summary, our results suggest that certain types of instructions cause subjects to employ strategies based on explicit reasoning— which are grounded in their perceptions and developed using the information provided in the instructions and training—to achieve the response they believe is requested by the experimenter.” This was all clearly known on the basis of prior experimence, as described in the introduction.
So, at any rate, the investigators express an interest in what is actually perceived by observers. But what is the question they're interested in answering? This is the real problem. The question, or goal, seems to be, “How do we measure color constancy?” But we don't measure things for measurement's sake. The natural follow-up is “Why do we want to measure color constancy?” What is the theoretical goal, or question we want to answer? This question matters because we can never, ever, arrive at some kind of universal, general, number for this phenomenon, which is totally condition-dependent. But I'm not able to discern, in these authors' work, any indication of their purpose in making these highly unreliable measurements.
Color constancy refers to the fact that sometimes, a surface “x” will continue to appear the same color even as the kind and intensity of the light it is projecting to the eye changes. On the other hand, it is equally possible for that same surface to appear to change color, even as the kind and intensity of the light it is reflecting to the eye remains the same. In both cases – constancy and inconstancy – the outcome depends on the total light projecting to the eye, and the way the visual system organizes it. In both cases – constancy and inconstancy – the visual principles mediating the outcome are the same.
The authors, in this and in previous studies, “measure constancy.” Sometimes it's higher, sometimes it's lower. It's condition-dependent. Even if they were actually measuring “constancy” in the sense of testing how an actually stable surface behaves under varying conditions, what would be the value of this data? We already know that constancy is condition-dependent, that it is often good or good enough, and that it can fail under certain well-understood conditions. (That these conditions are fairly well-understood is the reason the authors possess a graphics program for simulating “constancy” effects). How does simply measuring this rise and fall under random conditions (random because not guided by theory, meaning that the results won't help clarify any particular theoretical question) provide any useful information? What is, in short, the point?
Yet another twist in the plot is that in their experiments, the authors aren't actually measuring constancy. Because we are talking about simulations, in order to exhibit “constancy,” observes need (often) to actually judge two surface with different spectral characteristics as being the same. This criterion is based on assumptions made by the investigators as to what surfaces should look the same under different conditions/spectral properties. But this doesn't make sense. What does it mean, for example, if an observer returns “low constancy” results? It means that the conditions required for two actually spectrally different surfaces to appear the same simply didn't hold, in other words, that the investigators' assumptions as to the conditions that should produce this “constancy” result didn't hold. If the different stimuli were designed to actually test original assumptions about the specific conditions that do or do not produce constancy, fine. But this is not the case. The stimuli are simply and crudely labelled “simplified” and “more realistic.” This means nothing with respect to constancy-inducing conditions. Both of these kinds of stimuli can produce any degree of “constancy” or “inconstancy” you want.
In short, we know that color perception is condition-sensitive, and that some questions may fail to tap percepts; illustrating this this yet again is the most that this experiment can be said to have accomplished.
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On 2016 Jan 27, Lydia Maniatis commented:
A little way into their introduction, the authors of this article make the following clear and unequivocal assertion:
“These findings underscore the idea that the encoding of objects and shapes is accomplished by a hierarchical feedforward process along the ventral pathway (Cadieu et al., 2007; Serre, Kouh, Cadieu, Knoblich, & Krei- man, 2005; Serre, Oliva, & Poggio, 2007; Van Essen, Anderson, & Felleman, 1992). The question that arises is how local information detected in the early visual areas is integrated to encode more complex stimuli at subsequent stages.”
As all vision scientists are aware, the processes involved at every level of vision are both hierarchical and parallel, feedforward and feedback. These processes do not consist of summing “local information” to produce more complex percepts; a small local stimulus change can reconfigure the entire percept, even if the remaining “local information” is unchanged. This has been solidly established, on a perceptual and neural level, on the basis of experiment and logical argument, for many decades. (The authors' use of the term “complex stimuli,” rather than “complex percepts” is also misjudged, as all stimuli are simple in the sense that they stimulate individual, retinal photoreceptors in the same, simple way. Complexity arises as a result of processing - it is not a feature of the retinal (i.e. proximal) stimulus).
The inaccurate description of the visual process aligns with the authors' attempt to frame the problem of vision as a “summation” problem (using assumptions of signal detection theory), which, again, it decidedly is not. If the theoretical relevance of this study hinges on this inaccurate description, then it has no relevance. Even on its own terms, methodological problems render it without merit.
In order to apply their paradigm, the authors have constructed an unnatural task, highly challenging because of unnatural conditions - very brief exposures resulting in high levels of uncertainty by design, resulting in many errors, and employing unnaturally ambiguous stimuli. The task demands cut across detection, form perception, attention, and cognition (at the limit, where the subjects are instructed to guess, it is purely cognitive). (Such procedures may be common and old (“popular” according to the authors), but this on its own doesn't lend them theoretical merit).
On this basis, the investigators generate a dataset reflecting declining performance in the evermore difficult task. The prediction of their particular model seems to be generic: In terms of the type of models the authors are comparing, the probability of success appears to be 50/50; either a particular exponent (“beta”) in their psychometric function will decline, or it will be flat. (In a personal communication, one of the authors notes that no alternative model would predict a rising beta). The fitting is highly motivated and the criteria for success permissive. Half of the conditions produced non-significant results. Muscular and theory-neutral attempts to fit the data couldn't discover a value of “Q” to fit the model, so the authors “have chosen different values for each experiment,” ranging from 75 to 1,500. The data of one of five subjects were “extreme.” In addition, the results were “approximately half as strong as some previous reports, but “It ...remains somewhat of a mystery as to why the threshold versus signal area slopes found here are shallower than in previous studies, and why there is no difference in our study between the thresholds for Glass patterns and Gabor textures.” In other words, it is not known whether such results are replicable, and what mysterious forces are responsible for this lack of replicability.
It is not clear (to me) how a rough fit to a particular dataset, generated from an unnaturally challenging task implicating multiple, complex, methodologically/theoretically undifferentiated visual processes, of a model that makes such general, low-risk predictions (such as can be virtually assured by a-theoretical methodological choices) can elucidate questions of physiology or principle of the visual, or any, system.
Finally, although the authors state as their goal to decide whether their model “could be rejected as a model of signal integration in Glass pattern and Glass-pattern-like textures” (does this mean they think there are special mechanisms for such patterns?)” they do not claim to reject the only alternative that they compare (“linear summation”), only that “probability and not linear summation is the most likely basis for the detection of circular, orientation-defined textures.”
It is not clear what the “most likely” term means here. Most likely that their hypothesis about the visual system is true (what is the hypothesis)? Most likely to have fit their data better than the alternative? (If we take their analysis at face value, then this is 100% true). Is there a critical experiment that could allow us to reject one or the other? If no alternatives can be rejected, then what is the point of such exercises? If some can be, what would be the theoretical implications? Is there a value in simply knowing that a particular method can produce datasets that can be fit (more or less) to a particular algorithm?
The "summation" approach seen here is typical of an active and productive (in a manner of speaking) subdiscipline (e.g. Kingdom, F. A. A., Baldwin, A. S., & Schmidtmann, G. (2015). Modeling probability and additive summation for detection across multiple mecha- nisms under the assumptions of signal detection theory. Journal of Vision, 15(5):1, 1–16; Meese, T. S., & Summers, R. J. (2012). Theory and data for area summation of contrast with and without uncertainty: Evidence for a noisy energy model. Journal of Vision, 12(11):9, 1–28; Tyler, C. W., & Chen, C.-C. (2000). Signal detection theory in the 2AFC paradigm: Attention, channel uncertainty and probability summation. Vision Research, 40, 3121–3144.)
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On 2015 Dec 10, Lydia Maniatis commented:
This seems rather an odd choice of theme for a "Research Topic" in that it inspired a collection of papers with no conceptual coherence, out of many others that could have been selected on the basis of a common technique. It is somewhat like saying we'll put together an issue of physics papers that all used spectrometers. It's not really a "topic" unless you're specifically focussing on, e.g., pros and cons of the method.
The editors summary expresses the situation well: "In sum, this Research Topic issue shows several ways to use diverse kinds of noise to probe visual processing." As discussed in their exposition, noise has been historically used in multifarious ways for multifarious purposes.
I think the emphasis on technique rather than on theoretical problems is symptomatic of the conceptual impoverishment of the field. The use of the term "probe" has become common in this field, at least, indicating that a study is an exercise in a-theoretical data collection, rather than a methodic attempt to answer a question.
I would also add that noise as a technique to probe normal perception in normal conditions should be employed with caution, since it does not characterise normal scenes, but rather places unusual stress on the system which may respond in unusual ways.
Predictably, the results of the articles described seem undigested and of unclear value: E.g. "Hall et al. (2014) find that adding white noise increased the center spatial frequency of the letter-identification channel for large but not small letters;" (so...? how large is large...?) "Gold (2014) use pixel noise to investigate the visual information used by the observer during a size-contrast illusion. By correlating the observers頣lassification decision with each pixel of the noise stimuli, they find that the spatial region used to estimate the size of the target is influenced by the size of surrounding irrelevant elements" (or your theoretical definition of "irrelevant" needs adjustment).
If the goal of this issue was to show that you can make noise and get published, then it's a big success.
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On 2015 Nov 20, David Keller commented:
Why the blinding of experimental subjects should be tracked during a study, from start to finish
I wish to address the points raised by Folmer and Theodoroff in their reply [1] to my letter to the editor of JAMA Otolaryngology [2] concerning issues they encountered with unblinding of subjects in their trial of therapeutic MRI for tinnitus. These points are important to discuss, in order to help future investigators optimize the design of future studies of therapies for tinnitus, which are highly subject to the placebo, nocebo, Pygmalion and other expectation effects.
First, Folmer and Theodoroff object to my suggestion of asking the experimental subjects after each and every therapy session whether they think they have received active or sham placebo therapy in the trial so far (the "blinding question"). They quote an editorial by Park et al [3] which states that such frequent repetition of the blinding question might increase "non-compliance and dropout" by subjects. Park's statement is made without any supportive data, and appears to be based on pure conjecture, as is his recommendation that subjects be asked the blinding question only at the end of a clinical trial. I offer the following equally plausible conjecture: if you ask a subject the blinding question after each session, it will soon become a familiar part of the experimental routine, and will have no more effect on the subject's behavior than did his informed consent to be randomized to active treatment or placebo in the first place. Moreover, the experimenters will obtain valuable information about the evolution of the subjects' state of mind as the study progresses. We have no such data for the present study, which impairs our ability to interpret the subjects' answers to the blinding question, when it is asked only once at the end of the study.
Second, Folmer and Theodoroff state that I "misinterpreted" their explanation of why so many of their subjects guessed they had received placebo, even if they had experienced "significant improvement" in their tinnitus score. They object to my characterization of this phenomenon as due to the "smallness of the therapeutic benefit" of their intervention, but my wording summarizes their lengthier explanation, that their subjects had a prior expectation of much greater benefit, so subjects incorrectly guessed they had been randomized to sham therapy even if they exhibited a small but significant benefit from the active treatment. In other words, the "benefit" these subjects experienced was imperceptible to them, truly a distinction without a difference.
A therapeutic trial hopes for the opposite form of unblinding of subjects, which is when the treatment is so dramatically effective that the subjects who were randomized to active therapy are able to answer the blinding question with 100% accuracy.
Folmer and Theodoroff state that, in their experience, even if subjects with tinnitus "improve in several ways" due to treatment, some will still be disappointed if their tinnitus is not cured. Do these subjects then answer the blinding question by guessing they received placebo because their benefit was disappointing to them, imperceptible to them, as revenge against the trial itself, or for some other reason? Regardless, if you want to know how well they were blinded, independent of treatment effects and of treatment expectation effects, then you must ask them early in the trial, before treatment expectations have time to take hold. Ask the blinding question early and often. Clinical trials should not be afraid to collect data. Data are good; more data are better.
References:
1: Folmer RL, Theodoroff SM. Assessment of Blinding in a Tinnitus Treatment Trial-Reply. JAMA Otolaryngol Head Neck Surg. 2015 Nov 1;141(11):1031-1032. doi: 10.1001/jamaoto.2015.2422. PubMed PMID: 26583514.
2: Keller DL. Assessment of Blinding in a Tinnitus Treatment Trial. JAMA Otolaryngol Head Neck Surg. 2015 Nov 1;141(11):1031. doi: 10.1001/jamaoto.2015.2425. PubMed PMID: 26583513.
3: Park J, Bang H, Cañette I. Blinding in clinical trials, time to do it better. Complement Ther Med. 2008 Jun;16(3):121-3. doi: 10.1016/j.ctim.2008.05.001. Epub 2008 May 29. PubMed PMID: 18534323.
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On 2016 Apr 07, Lydia Maniatis commented:
Readers should read the last paragraphs of this article first. It indicates that the current results contradict the authors' previous results, and that they have no idea why that is. Nevertheless, they assume that one of the two must be right, and use a crude rule of thumb (the supposedly "simpler" explanation) to make their choice. I would take the third option.
"We see two possible explanations for the inconsistency between our previous work and that here:
The correct conclusions about the extent of contrast integration are drawn in our current work, with previous work being compromised by the loss of sensitivity with retinal eccentricity. For example, Baker and Meese (2011) built witch's hat compensation into their modeling, but not their stimuli (in which they manipulated carrier and modulator spatial frequencies, not diameter). A loss of experimental effect in the results (such as that in Figures 2a and 3a here) limits what the analysis can be expected to reveal. Indeed, Baker and Meese (2011) found it difficult to put a precise figure on the range of contrast integration, and aspects of their analysis hinted at a range of >20 cycles for two of their three observers. Baker and Meese (2014) made no allowance for eccentricity effects in their reverse correlation study. The contrast jitter applied to their target elements ensured they were above threshold, and so the effects of contrast constancy should come into play (Georgeson, 1991); however, we cannot rule out the possibilities that either (a) the contrast constancy process was incomplete or (b) internal noise effects not evident at detection threshold (e.g., signal dependent noise) compromised the conclusions.
The correct conclusions about the extent of contrast integration come from our previous work. Our current work points to lawful fourth-root summation, but not necessarily signal integration across the full range. On this account, signal integration takes place up to a diameter of about 12 cycles and a different fourth-root summation processes take place beyond that point. For example, from our results here we cannot rule out the following possibility: Beyond an eccentricity of ∼1.5° the transducer becomes linear and overall sensitivity improves by probability summation (Tyler & Chen, 2000), but uncertainty (Pelli, 1985; Meese & Summers, 2012) for more peripheral targets causes the slope of the psychometric function to remain steeper than β = 1.3 (May & Solomon, 2013).
We think Occam's razor would favor the first account over the second."
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On 2016 May 25, Lydia Maniatis commented:
When Todd et al say that understanding their demonstrations requires “a broader theoretical analysis of shape from shading that is more firmly grounded in ecological optics,” do they mean that there are things about the physics of how light interacts with surfaces that we don't understand? What kind of empirical investigations are they suggesting need to be performed? What kind of information do they think is missing, optically-speaking?
The fundamental issues are formal (having to do with form) not the details of optics and probabilities of illumination structure - as these authors have shown.
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On 2015 Nov 17, Johan van Schalkwyk commented:
SPRINT strikes me as a work of pure genius. Conceive the following scenario: Take a carefully selected mixture of high-risk patients with a variety of blood pressures and risk factors, making sure that the low threshold for selection into the study is below the current sytolic blood pressure 'standard' of 140 mmHg. Apply two protocols, one that will aggressively reduce blood pressure in the intermediate term, another that's far more conservative. It's not beyond the bounds of possibility that a group of smart statisticians using current simulation methods and access to large hypertension databases might even predict the intermediate-term outcomes with a fair degree of confidence.
The fact that this trial is exactly what every manufacturer of anti-hypertensives needs at this point, that it was stopped very early, and that it seems to contradict the prior evidence that has informed treatment guidelines to date should make us pause and think. Particularly as the results from a highly selected group, treated for a few years, may well be extrapolated to lifetime treatment of many or even most people with a systolic blood pressure of over 130 mmHg. Let's see how this is marketed.
You may well choose to ignore the fact that one of the principal authors has received "personal fees" and/or grants from Bayer, Boeringer Ingelheim, GSK, Merck, AstraZeneca, Novartis, Arbor, Amgen, Medtronic and Forest. Your choice. Everyone has to make a living.
Of greater concern might be the near tripling of the rate of acute kidney injury or acute renal failure in the intensive-treatment group, as these conditions are not cheap to manage. We might also be a bit puzzled that almost half of the "extra deaths" in the standard therapy group were NOT from cardiovascular causes. How on earth does this work?
But anyone who understands a bit about MCMC methods should be in awe of the way this study was put together.
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On 2016 Aug 27, Robert Goulden commented:
Hi David
Many thanks for your comments. Your key objection, in the comment here, your letter to Am J Med, and your PubMed commons comment on my response to that letter, is around the use of occasional drinkers as the reference category. You are completely right that this use of a reference category is the principal (but not sole) reason that I don’t find evidence of a benefit to moderate alcohol consumption. I had hoped that the use of this reference category was adequately explained in the paper, but it’s an important point so I’m happy to discuss it further.
Studies of the association between alcohol consumption and health are plagued with the problem of confounding. Non-drinkers and moderate drinkers differ in myriad important ways which conventional regression analyses cannot adequately adjust for (1). This leaves us with the difficult question of how to isolate the effects of alcohol on health, as opposed to the effect of all the other health-related variables which differ between non-drinkers and drinkers. One proposed solution is to use occasional drinkers as the reference category – not a novel “statistical maneuver” developed by me – but an approach used in the largest ever study of this question (2) (they were called light drinkers in that study, but the volume of alcohol consumed [0-2 g/day] meant they were occasional drinkers, as the accompanying editorial noted (3)). As I say in my paper, occasional drinkers “drink at levels for which a physiologic effect of alcohol is not plausible, but are likely to be more similar in other characteristics to moderate drinkers than long-term abstainers, thus reducing confounding”.
When this approach to addressing confounding is taken, my results are actually consistent with the wider literature, as Stockwell and Naimi note in their commentary on my paper (4). Their systematic review (5) reported “similar findings” and had my paper been included in their meta-analysis (it was published after their search window) it would have been coded as “high quality”. Other approaches which try to isolate the causal effect of alcohol and minimize confounding, such as mendelian randomization, also find no evidence of a benefit of moderate alcohol consumption (6).
Making sense of all the evidence is tricky, but my gut instinct (for what it's worth!), based on my paper and the wider literature, is that moderate alcohol consumption (up to 21 drinks per week) likely has very little effect (positive or negative) on health. My paper only finds unambiguous evidence of harm for those drinking over 21 drinks per week; of course, whether that association is driven by residual confounding is hard to say, but it’s certainly consistent with well-established links between heavy alcohol use and adverse outcomes such as liver disease, certain cancers, and trauma.
I think the claim that my abstract is ‘misleading’ isn’t warranted; I explicitly state in the abstract that occasional drinkers are the reference category, but by necessity this choice can only be fully explained in the main text.
Finally, you make some explicit causal claims about alcohol’s effects on health which I think go beyond what the observational literature can tell us. You state “the non-drinker can lower his Hazard Ratio for all-cause mortality…by starting the light consumption of alcohol” and “an average non-drinker can significantly lower their risk of call-cause mortality by adding one standard 14 gram serving of ethanol per day”. Until we have an RCT to demonstrate this, I think claims about what alcohol can and cannot do should be made more cautiously. If such a study were performed, and indeed showed benefit, I’d be the first to raise a glass to the results!
Regards,
Rob
References
1: Naimi TS, Brown DW, Brewer RD, Giles WH, Mensah G, Serdula MK, et al. Cardiovascular risk factors and confounders among nondrinking and moderate-drinking U.S. adults. Am J Prev Med. 2005 May;28(4):369–73.
2: Bergmann MM, Rehm J, Klipstein-Grobusch K, Boeing H, Schütze M, Drogan D, et al. The association of pattern of lifetime alcohol use and cause of death in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Int J Epidemiol. 2013 Dec 1;42(6):1772–90.
3: Stockwell T, Chikritzhs T. Commentary: Another serious challenge to the hypothesis that moderate drinking is good for health? Int J Epidemiol. 2013 Dec 1;42(6):1792–4.
4: Stockwell T, Naimi T. Study raises new doubts regarding the hypothesised health benefits of “moderate” alcohol use. Evid Based Med. 2016 Jul 7;ebmed-2016-110407.
5: Stockwell T, Zhao J, Panwar S, Roemer A, Naimi T, Chikritzhs T. Do “Moderate” Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality. J Stud Alcohol Drugs. 2016 Mar;77(2):185–98.
6: Holmes MV, Dale CE, Zuccolo L, Silverwood RJ, Guo Y, Ye Z, et al. Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data. BMJ. 2014;349:g4164.
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On 2015 Oct 09, Lydia Maniatis commented:
Dear Mike,
Take your time. I think our conversation has run its course. You believe that Taylor and Francis may have acted properly, that it is sometimes OK for a publisher to ban an author. I believe the opposite, to the point that I find it difficult to believe they were within their legal rights. If and when you find the time to inform yourself to your satisfaction about this particular case, we can continue the conversation.
If I had been particularly concerned with guarding my anonymity on PubPeer, you would have needed to be far more clever to unmask me. Your attempt to make this conversation about me (to label me as "highly emotional" - another evasive tactic on your part) and your triumph in "unmasking" me as Peer 14, as though this mattered (did I make any comments there I should be ashamed of?) is one of the reasons I support anonymity. Fortunately, my participation in future PubPeer discussions, when I choose to remain anonymous, won't be subject to such unworthy, ad hominem tactics.
Regards, Lydia
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On 2015 Oct 08, Michael R Blatt commented:
Dear Lydia:-
I can see that this is a highly emotionally-charged issue for you, whereas it appears less so for Jaime (though I can fully imagine why it might be otherwise). So, I do think it important to step back for a moment.
Let me relate another matter to you. This pertains to a case that goes back more than a quarter of a century and took place in a university in the mid-West of the United States. I was peripherally associated with the case, primarily because of my knowledge of the professor involved (a good friend, as it happens, and we remain so still). The professor, let’s call him Fred for now, became embroiled in an argument with his head of institute. The details of the argument are less important than the consequences. Fred was so aggrieved by the way he felt he had been treated, that he became disruptive, aggressive and threatening to other academic staff and students alike. In the end, following disciplinary proceedings, Fred was barred from the institute and took ‘early retirement.’ From my own perspective, I could understand why Fred was aggrieved – I, too, felt that the initial handling of the argument was problematic – but I could also see that his reaction was inappropriate and disproportionate, and that the institute had no choice but to bar him. In effect, Fred was within his rights, but was unwilling to accept responsibility for his actions and their consequences.
I am not suggesting that there is a parallel here, but I recall the story to point out that there are always two sides to an argument. In Fred’s case, I was close enough to the events that it was easy to see what was going on, from both sides. In Jaime’s case, I have gathered what information I can from RetractionWatch, but I note that the information is presented almost entirely from his perspective. In your insistence that I choose a side, do you really mean to deny me the right to hear both sides of the argument?
Bests,
Mike
p.s. I’ll need to attend to my own day job now, so it may be a few days before I respond to any more comments.
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On 2016 May 19, Lydia Maniatis commented:
Below is my reply to the author. My polemic tone notwithstanding, I appreciate his taking the time to respond. I've interspersed my responses with his text.
Author: A researcher I highly respect once told me that a good review paper is one that engages and stimulates the reader to think critically and broadly about a particular phenomenon. In this sense I appreciate the commentary by Prof. Maniatis, which suggests the review at least succeeded in stimulating critical thought in at least one distinguished reader. And I will add that, though my initial reaction was that Prof. Maniatis' commentary is a polemic, it is clear that my critic takes the issues very seriously and raises some important research questions suggesting future experimental work.
Me: My commentary is a polemic, if by that you mean it raises serious objections. I'm not recommending future work along the same lines; I'm saying the rationale for such work is vague to non-existent, not least because it conflicts with known facts. (My (ongoing) comments on Ariely (2001), which this article and many others treat as as “seminal,” as well as the other comments I've cited here, may make this clearer. Disagreement with the facts is supposed to be disqualifying in science, unless and until theoretical alignment can be achieved. Avoiding the (easy) possibility of falsification by choosing the route that Runeson describes (quoted in my second comment on Dube and Sekuler) is not the same thing as subjecting a hypotheses to serious tests. Inconclusive tests and an avoidance of critical discussion to point out logical inconsistencies/inconsistencies with the phenomena ensures that more work is always needed.
Author: Nonetheless, the response, roughly a third of which seems to revolve around a passing reference to work by Koffka that has little to no bearing on the main points and conclusions of the review (and which misses the point of the reference to Koffka)...
Me: If I've missed the point, then please let me know what I've missed. I consider the mistake that I flagged serious because it implies that the work of the Gestaltists supports the work being discussed here, when in fact the opposite is true.
Author:...contains a number of misintepretations of the points made in the review. I take responsibility for any lack of clarity that may have produced this. I will detail a couple of examples that seem most directly related to the review (discussion of modeling methods, which don't fit algorithms as Prof. Maniatis stated but use algorithms to fit models, has to do with standard practice in the field itself and not the review).
Me: Standard practice isn't necessarily good practice.
Author: Encoding and retrieval of statistical information about stimuli, such as the average diameter of circles in a set of circles with different diameters, may or may not involve direct "perception" of the average in the sense used by Prof. Maniatis. The relevant experiments, I suspect, have yet to be conducted.
Me: Encoding and retrieval of statistical information about stimuli, such as the average diameter of circles, may or may not actually happen. Scientific hypotheses are indeed guesses, but to be worthy of testing there needs to be a rationale and a clear articulation of associated assumptions. Relevant experiments pre-suppose that the idea has been developed enough to specify, for the purpose of testing, what these assumptions are. If investigators, after decades, haven't even decided whether direct perception is involved (which it clearly isn't – it's the nature of direct perception to be self-evident), then what have they been doing?
Author: For this reason, "perceptual" may not be the best term and several different terms for the effects we have described are in in use (ensemble representation, statistical summary representation, etc). In my prior work (Dubé et al., 2014) I have discussed conceptual difficulties related to this term, and in my current work I favor "statistical summary representation" for this reason. However, the findings detailed in the review are indisputable.
Me: I dispute them, partly along the lines of Runeson. I think when we look on a case by case basis, we find serious problems of method and/or misrepresentations in the interpretation.
Author: There is a clear consensus in the literature that participants can accurately recall the average.
Me: It's interesting that experimenters jump to the recall stage but skip the (presumably less challenging) perception stage. Why are observers being forced to recall what they are supposed to be perceiving?
Author: If they can accurately recall it, they must have encoded and stored it. There is no question as to whether such memories exist. I just returned from VSS at which there were around 50 presentations on the topic of summary statistical representation, according to one talk, and the special issue of JoV in which our review appeared was devoted entirely to summary statistical representation. Clearly a decent number of scientists remains convinced that the effects exist!
Me: Numbers of proponents is not an argument. I've criticized some of these authors' work, and when there's a response its not very convincing.
Author: The final comment in the review, which Prof. Maniatis takes as our own admission that the existence of statistical representation is questionable, was meant to be somewhat tongue-in-cheek. How can the effects that have been attributed to remembered averages be due to memory for fine details of individual items when several studies, including the seminal one by Ariely (2001), demonstrate memory for the average despite chance performance on memory tests of the individual items from which the average was computed?
Me: I'm in the process of commenting on Ariely (2001). His methods and interpretations are questionable and his arguments are full of inaccuracies and inconsistencies. It is an extremely casual, not a seminal, study.
Author: It is in no way a statement that the effects don't exist (or even that we suspect they don't), even if taken at face value, and as I have detailed there is a quite large amount of empirical evidence to contradict the philosophical position of Prof. Maniatis. I will not detail all of these studies here, since a review detailing them already exists: Dubé and Sekuler (2015).
Me: There are often other ways to interpret performances that have been attributed to some kind of mental calculation. The brain can use rules of thumb, as Gigerenzer has discussed. One example is how baseball players can catch a ball without subconsciously doing the complex math that some thought was required. When you a. ignore falsifying facts and b. don't consider alternative interpretations, then you have no doubts.
Author: In my view, the conceptual nuances involved in discussion of summary statistical representation are suggestive of a need for more concrete, computational modeling, less verbal theorizing, and more neural data in this area."
Me: If by verbal theorizing you mean critical discussion and exchange of ideas, I would say that more is desperately needed. The conceptual problems aren't “nuances,” they're huge. Useful data collection presupposes clear theories; otherwise its a waste of time, money and people. (As Darwin said, if you don't have a hypothesis, you might as well count the stones on Brighton Beach). The normalized view (espoused by journal editors) that critical discussion is the enemy of progress is convenient, but unscientific and wasteful.
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On 2016 May 18, Chad Dube commented:
A researcher I highly respect once told me that a good review paper is one that engages and stimulates the reader to think critically and broadly about a particular phenomenon. In this sense I appreciate the commentary by Prof. Maniatis, which suggests the review at least succeeded in stimulating critical thought in at least one distinguished reader. And I will add that, though my initial reaction was that Prof. Maniatis' commentary is a polemic, it is clear that my critic takes the issues very seriously and raises some important research questions suggesting future experimental work. Nonetheless, the response, roughly a third of which seems to revolve around a passing reference to work by Koffka that has little to no bearing on the main points and conclusions of the review (and which misses the point of the reference to Koffka), contains a number of misintepretations of the points made in the review. I take responsibility for any lack of clarity that may have produced this.
I will detail a couple of examples that seem most directly related to the review (discussion of modeling methods, which don't fit algorithms as Prof. Maniatis stated but use algorithms to fit models, has to do with standard practice in the field itself and not the review).
Encoding and retrieval of statistical information about stimuli, such as the average diameter of circles in a set of circles with different diameters, may or may not involve direct "perception" of the average in the sense used by Prof. Maniatis. The relevant experiments, I suspect, have yet to be conducted. For this reason, "perceptual" may not be the best term and several different terms for the effects we have described are in in use (ensemble representation, statistical summary representation, etc). In my prior work (Dubé et al., 2014) I have discussed conceptual difficulties related to this term, and in my current work I favor "statistical summary representation" for this reason. However, the findings detailed in the review are indisputable. There is a clear consensus in the literature that participants can accurately recall the average. If they can accurately recall it, they must have encoded and stored it. There is no question as to whether such memories exist. I just returned from VSS at which there were around 50 presentations on the topic of summary statistical representation, according to one talk, and the special issue of JoV in which our review appeared was devoted entirely to summary statistical representation. Clearly a decent number of scientists remains convinced that the effects exist!
The final comment in the review, which Prof. Maniatis takes as our own admission that the existence of statistical representation is questionable, was meant to be somewhat tongue-in-cheek. How can the effects that have been attributed to remembered averages be due to memory for fine details of individual items when several studies, including the seminal one by Ariely (2001), demonstrate memory for the average despite chance performance on memory tests of the individual items from which the average was computed? It is in no way a statement that the effects don't exist (or even that we suspect they don't), even if taken at face value, and as I have detailed there is a quite large amount of empirical evidence to contradict the philosophical position of Prof. Maniatis. I will not detail all of these studies here, since a review detailing them already exists: Dubé and Sekuler (2015).
In my view, the conceptual nuances involved in discussion of summary statistical representation are suggestive of a need for more concrete, computational modeling, less verbal theorizing, and more neural data in this area.
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On 2015 Sep 16, Morgan E Levine commented:
Daniel Himmelstein, thank you for your comments. I will try to address them to the best of my ability.
We acknowledge that the sample size is very small, which we mention in our limitations section of the paper. Because we are studying such a rare phenotype, there is not much that can be done about this. “Long-lived smokers” is a phenotype that has been the subject of a number of our papers, and that we think has strong genetic underpinnings. Despite the small sample size, we decided to go ahead and see if we could detect a signal, since there is evidence to suggest that the genetic influence may be larger for this phenotype compared to many others—something we discuss at length in our introduction section.
To the best of our knowledge the finding that highly connected genes contain more SNPs, has not been published in a peer-reviewed journal. Therefore, we had no way of knowing or evaluating the importance of this for our study. Similarly, we used commonly used networks and do acknowledge the limitations of these networks in our discussion section. The network you link to was not available at the time this manuscript was accepted.
We acknowledge the likelihood of over-fitting in our PRS, which is probably due to our sample size. This score did validate in two independent samples. Therefore, while it is likely not perfect, we feel that it may still capture some of the true underlying signal. We followed standard protocol for calculating our score (which we reference). In the literature there are many examples of scores that have been generated by linearly combining information from SNPs that are below a given p-value threshold in a GWAS. While, not all of these replicate, many do. Our study used very similar methods, but just introduced one additional SNP selection criteria—SNPs had to also be in genes that were part of an FI network. I don't think this last criteria would introduce additional bias that would cause a type I error in the replication analysis. However, we still recognize and mention some of the limitations of our PRS. We make no claim that the score is free from error/noise or that it should be used in a clinical setting. In fact, in the paper we suggest future methods that can be used to generate better scores.
We feel we have provided sufficient information for replication of our study. The minor alleles we used are consistent with those reported for CEU populations, which is information that is readily available. Thus, the only information we provide in Table S2 pertain to things specific to our study, that can't be found elsewhere. Lastly, the binning of ages is not 'bizarre' from a biogerontology and longevity research perspective. A number of leaders in the filed have hypothesized that the association between genes and lifespan is not linear (variants that influence survival to age 100+ are not the same as variants that influence survival to age 80+). Thus, using a linear model would not be appropriate in this case and instead we selected to look at survival by age group.
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On 2017 Feb 18, Clive Bates commented:
Erroneous interpretations have been placed on these results and overly confident conclusions drawn from very small numbers of imperfectly characterised teenagers. The headline recommendations were based on the behaviour of six out of 16 baseline e-cigarette users in a sample of 694 adolescents deemed not to be susceptible to smoking. Large conclusions drawn from small numbers should always be a cause for caution, as discussed in this article about this study by Five Thirty-Eight:
Ignore The Headlines: We Don’t Know If E-Cigs Lead Kids To Real Cigs by Christie Ashwandan, 11 September 2015
One should expect the inclination to use e-cigarettes to be caused by the same things that cause an inclination to smoke - they are similar habits (the former much less risky) and it is quite likely that those who used e-cigarettes first would have become smokers first in the absence of e-cigarettes - a concept known as shared liability. A range of independent factors that create a common propensity to smoke or vape, such as parental smoking, rebellious nature, delinquency etc. explain the association between vaping and smoking incidence but without this relationship being causal.
The authors try to address this by characterising teenagers non-susceptible to smoking if they answer “definitely no” when asked the following: “If one of your friends offered you a cigarette, would you try it?” and “Do you think you will smoke a cigarette sometime in the next year?”. The study concentrates on this group.
This is not a foolproof way of characterising susceptibility to smoking, which in any case is not a binary construct but a probability distribution. Nor is susceptibility a permanent condition for any young person - for example, if a teenage girl starts seeing a new boyfriend who smokes that will materially changes her susceptibility to smoking. The fact that some were deemed unsusceptible to smoking but were already e-cigarette users is grounds for further unease - these would be more likely to be the teens where the crude characterisation failed.
It is a near-universal feature of tobacco control research that the study presented is a wholly inadequate basis for any policy recommendation drawn in the conclusion, and this study is no exception:
These findings support regulations to limit sales and decrease the appeal of e-cigarettes to adolescents and young adults.
The findings do not support this recommendation, not least because the paper is concerned exclusively with the behaviour of young people deemed not susceptible to smoking and, within that group, a tiny fraction who progressed from vaping to smoking. Even for this group (6 of 16) the authors cannot be sure this isn't a result of mischaracterisation and that they would not have smoked in the absence of e-cigarettes. The approach to characterising non-susceptibility is far too crude and the numbers involved far too small to draw any policy-relevant conclusions.
But this isn't the main limitation. Much more troubling is that the authors made this policy recommendation without considering the transitions among young people who are susceptible to smoking - i.e. those more likely to smoke, and also those much more likely to use e-cigarettes as well as or instead of smoking. This group is much more likely to benefit from using e-cigarettes as an alternative to smoking initiation, to quit smoking or cut down or as a later transition as they approach adult life.
There are already findings (Friedman AS, 2015, Pesko MF, 2016, Pesko MF, Currie JM, 2016) that regulation of the type proposed by the authors designed to reduce access to e-cigarettes by young people has had unintended consequences in the form of increased smoking - something that should not be a surprise given these products are substitutes. While one may debate these findings, the current study makes no assessment of such effects and does not even cover the population that would be harmed by them. With these limitations, it cannot underpin its own over-confident and sweeping policy recommendation.
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On 2016 May 17, Annika Hoyer commented:
With great interest we noticed this paper by Nikoloulopoulos. The author proposes an approach for the meta-analysis of diagnostic accuracy studies modelling random effects while using copulas. In his work, he compares his model to the copula approach presented by Kuss et al. [1], referred to henceforth as KHS model. We appreciate a lot Nikoloulopoulos referring to our work, but we feel there are some open questions.
The author shows in the appendix that the association parameter from the copula is estimated with large biases from the KHS model, and this is what we also saw in our simulation study. However, the association parameter is not the parameter of main interest which are the overall sensitivities and specificities. They were estimated well in the KHS model, and we considered the copula parameter more as a nuisance parameter. This was also pointed out by Nikoloulopoulos in his paper. As a consequence, we are thus surprised that the bad performance in terms of the association parameter led the author to the verdict that the KHS method is 'inefficient' and 'flawed' and should no longer be used. We do not agree here, because our simulation as well as your theoretical results do clearly show that the KHS estimates the parameters of actual interest very well. Just aside, we saw compromised results for the association parameter also for the GLMM model in our simulation.
Nikoloulopoulos also wrote that the KHS approximation can only be used if the 'number of observations in the respective study group of healthy and diseased probands is the same for each study'. This claim is done at least 3 times in the article. But, unfortunately, there is no proof or reference or at least an example which supports this statement. Without a mathematical proof, we think there could be a misunderstanding in the model. In our model, we assume beta-binomial distributions for the true positives and the true negatives of the i-th study. They were linked using a copula. This happens on the individual study level because we wanted to account for different study sizes. For estimating the meta-analytic parameters of interest we assume that the shape and scale parameters of the beta-binomial distributions as well as the copula parameter are the same across studies, so that the expectation values of the marginal distributions can be treated as the meta-analytic sensitivities and specificities. Of course, it is true that we used equal sample sizes in our simulation [1], however, we see no theoretical reason why different sample sizes should not work. In a recently accepted follow up paper on trivariate copulas [2] we used differing sample sizes in the simulation and we also saw a superior performance of the KHS model as compared to the GLMM. In a follow-up paper of Nikoloulopoulos [3], he repeats this issue with equal group sizes, but, unfortunately, did not answer our question [4,5] with respect to that point.
As the main advantage of the KHS over the GLMM model we see its robustness. Our SAS NLMIXED code for the copula models converged better than PQL estimation (SAS PROC GLIMMIX) and much better that Gauss-Hermite-Quadrature estimation for the GLMM model (SAS PROC NLMIXED). This was true for the original bivariate KHS model, but also for the recent trivariate update. This is certainly to be expected because fitting the KHS model reduces essentially to the fit of a bivariate distribution, but without the complicated computations or approximations for the random effects as it is required for the GLMM and the model of Nikoloulopoulos given here. Numerical problems are also frequently observed if one uses the already existing methods for copula models with non-normal random effects from Liu and Yu [6]. It would be thus very interesting to learn how the authors’ model performs in terms of robustness.
Annika Hoyer, Oliver Kuss
References
[1] Kuss O, Hoyer A, Solms A. Meta-analysis for diagnostic accuracy studies: A new statistical model using beta-binomial distributions and bivariate copulas. Statistics in Medicine 2014; 33(1):17-30. DOI: 10.1002/sim.5909
[2] Hoyer A, Kuss O. Statistical methods for meta-analysis of diagnostic tests accounting for prevalence - A new model using trivariate copulas. Statistics in Medicine 2015; 34(11):1912-24. DOI: 10.1002/sim.6463
[3] Nikoloulopoulos AK. A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence. Statistical Methods in Medical Research 2015 11 Aug; Epub ahead of print
[4] Hoyer A, Kuss O. Comment on 'A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence' by Aristidis K Nikoloulopoulos. Statistical Methods in Medical Research 2016; 25(2):985-7. DOI: 10.1177/0962280216640628
[5] Nikoloulopoulos AK. Comment on 'A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence'. Statistical Methods in Medical Research 2016; 25(2):988-91. DOI: 10.1177/0962280216630190
[6] Liu L, Yu Z. A likelihood reformulation method in non-normal random effects models. Statistics in Medicine 2008; 27(16):3105-3124.
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On 2015 Aug 12, Liam McKeever commented:
Dear Ms. Gluck,
Thank you for your comments. Training in the use of multiple databases was not the point of this paper. This paper was written in response to a recognition that many of the methods researchers use to perform their systematic reviews are not in fact systematic. A systematic review is meant to bring scientific methods into the process of writing a review. This means the methods of the review must be reproducible. Currently, many reviews that attempt to be truly systematic employ only the MEDLINE database because of its organized system of medical subject headings. If they do this correctly, they can perform an exhaustive search of the MEDLINE database. Our paper provided a technique for taking this systematic approach into an exhaustive search of both the MEDLINE and the PubMed databases, leading to a master formula, which could then be picked apart and improved upon by the scientific community. The techniques translate well to other databases and have recently been translated to EMBASE.
The argument that a complete systematic review should include an attempt to collect all relevant articles from multiple databases is well taken and commonly accepted. Preventing publication bias however is a much bigger picture than including multiple databases in a search strategy and was beyond the scope of this paper. To get all the null findings necessary to overcome publication bias would also mean including studies that either never entered or did not survive the peer review process. While such attempts should be made, a more achievable goal would be the thorough analysis of the publication bias present in a review where the search methodology is both explicit and reproducible.
The selection of appropriate databases for a systematic review, as you implied, varies greatly by profession. It was therefore also not in the scope of this paper. I do think there is some value in considering what it actually means than not all databases contain all journals. I find it highly unlikely that a bio-medically relevant journal would not be indexed in MEDLINE simply because they neglected to apply. It is much more likely that they applied and were rejected. Just as a systematic review has inclusion criteria at the level of the articles selected, databases have inclusion criteria at the level of the journals selected for cataloging. The degree of research quality and scope of topic areas are considered and determined to either meet or not meet the standards of the database. When we select a database for a systematic review, we are defining our inclusion criteria at the level of the journal. With this in mind, assuming adequate search methods were used and provided a thorough analysis of publication bias has been performed, one could make the argument that a properly selected major database pairing, like MEDLINE and PubMed may be acceptable for a systematic review. From a scientific methods perspective, we feel what is most important is that the inclusion criteria at all levels are explicit and that is what this paper attempts to facilitate.
Sincerely, Liam McKeever, MS, RDN
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On 2016 May 23, Stanton A Glantz commented:
In June 2015 we published our paper “The smoking population in the USA and EU is softening not hardening” in the journal Tobacco Control. We showed that as smoking prevalence has declined over time, quit attempts increased in the USA and remained stable in Europe, US quit ratios increased (no data for EU), and consumption dropped in the USA and Europe. These results contradict the hardening hypothesis which is often used as part of the tobacco industry’s strategy to avoid meaningful regulation and protect its political agenda and markets, claiming that there is a need for harm reduction among those smokers who “cannot or will not quit.” Indeed, rather than “hardening” the remaining smoking population is “softening.”
In February 2016 we received an email from Robert West, editor of the journal Addiction, informing us that Addiction was about to publish an article by Plurphanswat and Rodu entitled “A Critique of Kulik and Glantz: Is the smoking population in the US really softening?” whose sole purpose was to critique our Tobacco Control paper, and offered to let us respond to the criticism.
The fact that Plurphanswat and Rodu sent their paper to Addiction was unusual because normal scientific procedure would have had them sending a letter to the editor of the journal that originally published the work (Tobacco Control).
As detailed below, we did respond, noting that Plurphanswat and Rodu’s paper followed the well-established pattern of tobacco industry-funded researchers trying to create controversy about research inconsistent with industry interests, the fact that Rodu had understated his financial ties to the industry, and, of course, showing how their criticism was based on statistical error that they made.
Addiction rejected our response because we would not delete the first two points and limit our response only to the statistical issue.
This blog post includes the response that Addiction rejected so that readers of Plurphanswat and Rodu’s critique do not think we did not have a response. We also include a summary of our interactions with the journal and the related email correspondence.
THE REJECTED RESPONSE
Consider the Source
“Harm reduction” is a key part of the tobacco industry’s strategy to avoid meaningful regulation and protect its political agenda and markets.[1] This agenda is premised on the existence of “hard core” smokers who “cannot or will not” quit.[2-4] Our paper, “The smoking population in the USA and EU is softening not hardening”,[5] undermined this agenda because it showed that, contrary to the hardening hypothesis, as smoking prevalence has declined over time, quit attempts increased in the USA and remained stable in Europe, US quit ratios increased (no data for EU), and consumption dropped in the USA and Europe.
There is a longstanding pattern of tobacco industry-funded experts writing letters criticizing work that threatens the industry’s position, first described in 1993 by then-JAMA Deputy Editor Drummond Rennie.[6] Rodu and various co-authors have written several such letters.[7-10] Another similarity to past efforts is industry-linked experts submitting critiques of a paper published in one journal to another,[11-15] which is also the case here, with this critique of our paper published in Tobacco Control being published in Addiction. One would have expected any criticism to have been published as a letter in Tobacco Control.
Addiction requires “full disclosure of potential conflicts of interest, including any fees, expenses, funding or other benefits received from any interested party or organisation connected with that party, whether or not connected with the letter or the article that is the subject of discussion.” As with another investigator supported by the tobacco industry,[16] the conflict of interest statement Plurphanswat and Rodu provide may not truly reflect the extent of Rodu’s involvement with the tobacco industry. For example:
• Rodu’s Endowed Chair in Tobacco Harm Reduction Research at the University of Louisville is funded by the U.S. Smokeless Tobacco Company (US Tobacco) and Swedish Match North America, Inc.[17]
• Rodu is a Senior Fellow at the Heartland Institute, which has received tobacco industry funding.[18-20]
• Rodu is a Member and Contributor to the R Street Institute, which has received tobacco industry funding.[19,21]
• Before moving to Louisville, Dr. Rodu was supported in part by an unrestricted gift from the United States Smokeless Tobacco Company to the Tobacco Research Fund of the University of Alabama at Birmingham.[8]
• Rodu was a keynote speaker at the 2013 Tobacco Plus Expo International, a tobacco industry trade fair to discuss “How has the tobacco retail business evolved; where was it fifteen years ago, where is it today and where is it going”.[22]
• Rodu has worked with RJ Reynolds executives between at least 2000 and 2009 to help promote industry positions on harm reduction, including specific products.[23-26]
The substance of Plurphanswat and Rodu’s criticism is that the statistically significant negative association between smoking prevalence and quit attempts and the positive association between prevalence and cigarettes smoked per day both become non-significant when more tobacco control variables are included in the model (state fixed effects, cigarette excise taxes, workplace smoking bans and home smoking bans). The problem with including all these variables is that it results in a seriously overspecified model, which splits any actual effects between so many variables that all the results become nonsignificant. The regression diagnostic for this multicollinearity is the Variance Inflation Factor (VIF); values of the VIF above 4 indicate serious multicollinearity. For the United States, adding all the other variables increases the VIF for the effect of changes in smoking prevalence from 1.8 in our model for quit attempts to 16.7, and from 1.8 in our model to 17.9 for cigarettes per day, respectively. Plurphanswat and Rodu’s model is a textbook case of why one has to be careful not to put too many variables in a multiple regression.
The Plurphanswat and Rodu criticism misrepresents our conclusions. We did not argue that drops in prevalence caused increased quit attempts and reduced consumption; we simply present the observation that, as prevalence falls, quit attempts increase and consumption fall or remain constant, which is the exact opposite of what the hardening hypothesis predicts.
The references and the full email correspondence with Addiction is available at http://tobacco.ucsf.edu/addiction-refuses-allow-discussion-industry-ties-criticism-our-“softening-paper”
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On 2015 Nov 10, Toni Schneider commented:
The comment of Marco Weiergräber is full of speculation. But scientific progress depends on careful control of novel hypotheses, especially when results of a similar research project are opposite. Scientific reports must mention opposite results, when new data are published. Siwek et al (Sleep 2014 May 1;37(5):881-92) did not refer to our results published a year earlier (Somnologie, September 2013, Volume 17, Issue 3, pp 185-192) but they speculate since then in an unscientific manner about our data, which were presented in our publication in an absolute transparent way (single data, in parallel to the resulting mean values). Our data are as reliable as the data from Siwek et al (2014). Taking this premise serious, one has to think about reasons for differences of results in an objective way. Two different mouse models were used in the two sleep studies mentioned. Logically, one must look for differences in these two mouse models, which we have discussed in an objective and fair way, without questioning the careful investigation done by Siwek et al (2014). To think about the different remnants left in the two different Cav2.3-knockout mouse lines should generate new hypotheses instead of condemning the results of a competing laboratory. We estimate the risk of an aminoterminal Cav2.3-peptide (resulting from the expression of exon 1) lower to contribute to calcium current disturbances as the risk of a "hemichannel".
The last chapter of Marco Weiergräber's comments also stays speculative, as long as he has not tested the transfer capacity of the transmitter device under discussion (a F20EET radiotransmitter from DSI). We tested the frequency bands under standardized conditions and can confirm that the bandwidth is broader than mentioned by him. Instead of repeating again and again the same critisism without mentioning e.g. a correction published by us (Schneider T. and Dibué M., 2015 in Somnologie 17, 307-308) and without presenting new proofing data, it seems to be a fight for something else but not for progress in Science.
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On 2015 Sep 06, Lydia Maniatis commented:
The claims of Blakeslee and McCourt are flawed on logical, methodological, theoretical, and empirical grounds.
Perhaps the core error is the denial of perceptual facts, as described below (and as noted also by Gilchrist in his commentary on this article).
In the Adelson checker-shadow illusion (to take one example), a check in apparent shadow looks white, while an equiluminant check, apparently in plain view, looks black. Aside from the additional presence of the apparent shadow, the experience of the two surfaces is similar to looking at a white check and at a black check under homogeneous illumination. Kohler (1935), describes a “real-world” version wherein a white and a black paper appear white and black, respectively, even if the illumination is adjusted so that the two surfaces are actually equiluminant.
Imagine, now, what would happen if we asked a naive observer to report on “the intensity of the light coming from the surface of each of the two checks.” First, he or she would likely assume the question referred to the apparent illumination of the surfaces. In this case, the white, “shadowed” check should receive a lower rating than the black “plain-view” one. If we then tried to clarify that we want the observer to make matches based on “the amount of light each surface is sending to the eye,” (its luminance) I think the observer would have trouble a. understanding what we are asking and b. performing the required task. And I'm not sure anyone would be able to judge, with confidence, whether the two checks in the Adelson checkerboard are, or are not, in fact equiluminant. That's what makes the demo so impressive. Even if observers could estimate this value, the task would be difficult and the results unreliable. To achieve it, they would have to focus narrowly on each square, isolating it from the surround.
Yet, Blakeslee and McCourt maintain that the latter task, which requires viewers to overide their spontaneous, salient perceptual experience, is “strictly based on appearance,” while the former, effortless experience is “based on an inferential judgment.” If, however, we define “appearance” as “what something looks like,” then the authors' arguments are obviously false, as can be confirmed by any observer.
The authors' argue that the experience which is quite literally based on appearance, is actually a product of learning. This is a major claim (implying that learning can actually alter a percept from black to white), but the authors offer no evidence for it. All of the arguments and available evidence is against. As Gilchrist (2015) points out, even fish seem to naturally achieve this kind of learning. A child can see the Adelson checker-shadow effect as effortlessly as an adult. Our perceptions aren't affected by what we learn about the nature of light and the properties of surfaces, we don't have to learn how to judge when a surface is in shadow or merely darker than its neighbor, or when it is covered by various types of transparency, we don't even have to learn that at night things don't actually change color. Given the difficulty scientists have in analyzing and modelling percieved lightness, and given that massive, early exposure to artificial images mimicking illumination variation has no discernible effect on our perception of the “real” world, the claim that people go through a process of learning to make the inferences necessary to achieve veridical percepts in natural conditions does not seem credible. B and M have certainly not tested it.
The quality that the authors argue is “strictly based on appearance” is a quality that they term “brightness,” defined as the perceptual correlate of luminance. The view that there is a perceptual correlate of luminance seems to be uncontroversial among lightness researchers (e.g. Kingdom, 2011; Gilchrist, 1999)), although Anderson (2014) seems to define brightness (more properly, in my opinion) as apparent illumination. The claim seems easy to refute.
Suppose we observe a set of surfaces lacking cues to differential illumination, and that some appear white, some gray, some black. Suppose, then, that we observe the same set of surfaces, at a different time, under a different degree of illumination. Assume that have completely forgotten the previous experience with the surfaces, and are again asked to judge their white/gray/black character. Our responses will typically be similar to those we gave in the first (now forgotten) instance. In other words, even though the illumination (and consequently the luminance) of the surfaces will have changed, our responses will remain the same. If the range of luminances is complete enough, they will, in both cases, be correlated with reflectance and not with luminance. Thus, even under homogeneous illumination, we cannot say that we are perceiving luminance, or that perception is more direct than in other situations. As always, the percept is the product of a complex visual process based on luminance values and structural assumptions.
When it comes to the case of non-homogenous (apparent) illumination, the authors seem to be treating illumination boundaries as though they were directly-perceived facts serving to support “inferentially” perceived lightness judgments. They say, for example, that “when the illumination component is clearly visible” the observer can use “brightness contrast” at the boundary to infer the magnitude of the illumination. There are a number of problems with this description.
First, if a shadow is perceived – is “clearly visible” - as the cause of the luminance boundary, then viewers are perceiving a double-layer – a surface with lightness x and an apparent shadow of darkness y lying on top of it. They are not perceiving a single “brightness” value. The authors are using the term “brightness” when they actually mean luminance.
Relatedly, the illumination boundary only becomes “clearly visible” after the visual process has inferred its presence based on the luminance structure – including the relative luminances at luminance boundaries - of the image. Whether the darker side of an edge will be perceived as being similar in reflectance, but lower in illumination than its neighbor, or as darker than its neighbor due to a lower reflectance, or any other combination of possibilities, depends on the global structure of the image. Given certain conditions, even a non-existent luminance edge may produce an apparent lightness difference, as in the case of illusory surfaces. So the argument that perceiving a surface as continuing beneath a “shadow” boundary is more inferential than perceiving a particular surface as gray due to its luminance relative to other surfaces in an image is naive. If “appearance-based” means “based on luminances”, then all perception is appearance-based. If it means that surfaces are perceived based on local luminance conditions, then it never is. Local conditions do not even determine photoreceptor activity in the horseshoe crab.
As corroborating evidence, the authors point to a few references, including Blakeslee and McCourt (2008), which is supposed to prove the existence of “brightness” judgments. Their stimuli consist of the classic simultaneous contrast demo plus variations that create weak impressions of differential illumination. The “brightness” judgments are defined as those that arise when observers are instructed to focus narrowly on the targets. This is similar to applying a mask. Effectively, we are talking about the same visual process acting on a different stimulus, not about a different type of judgment. Due to the weakness of the structural cues to differential illumination in B and M's (2008) stimuli, the ability of observers to isolate the target in this way is very easy. The demand would be much more difficult, and the results surely very different, if the stimulus had been the Adelson checkerboard.
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On 2016 Jan 29, Martin Pusic commented:
Thank you for this insightful review - we're glad that the article created such a rich discussion. Here are a couple of other thoughts:
. "different tracks for different learners" - what a learning curve makes manifest is the time component of an assessment. As a medical educators, we have the privilege of teaching highly motivated learners who almost always get over whatever bar we set for them. If we grade ourselves as teachers by counting how many learners get over the bar, it is easy to perceive ourselves as successful; however, if instead we grade ourselves on the SLOPE of the learning curve, now we have a metric that challenges us to grade our efforts in terms of learning efficiency, which is amount of learning per unit of learning effort expended. This does three good things: 1) it orients us towards maximizing the most precious student commodity - time; 2) it prompts educators to consider more closely the PROCESS of learning as that's how you improve the slope and 3) it allows us to use the variability in paths/slopes to learn the best ways of teaching and learning. So it may be that we do not need customized learner development charts, as well as those work for pediatrics, but rather to learn from those outliers who fall away from the average curve so as to feed that back into the system to improve the learning for everyone.
.in the "life-cycle of clinical education" we would also encourage you consider the asymptote. The asymptote defines the "potential" of a learning system. "How good can we possibly be, if we used this system an infinite number of times?" Improving the slope means we get people up to competence more efficiently. Improving the asymptote means we get even better competence. In some cases we only need "x" amount of minimum competence and we're fine (think hand washing); but in most areas of medicine, we can always do better. The path to competence is all-important, but our learning systems would do well to also map out the path from competence to excellence, defined as being the very best any of us can be. The asymptote, along with the very shallow slope of the learning curve as it approaches it, gives us an idea of what excellence takes.
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On 2015 Jan 22, Yuriy Pankratov commented:
This discussion could be more enlightening and even reach a consensus of some sort if our respected opponents, instead of making ungrounded accusations and avoiding inconvenient facts, tried to address the most serious issues, raised in our comments at PubMed Common and JNS website. These issues include: stark contradiction between the EGFP and LacZ expression phenotypes shown in Fujita et al. and data shown in previous publications (all of which went through rigorous peer review by the way); lack of direct evidence of notable impairment of synaptic transmission in dnSNARE mice and existence of clear evidence of the opposite; large pool of evidence supporting physiological role of astroglial exocytosis which does not rely on the dnSNARE mice at all. Neither paper itself nor Authors’ responses to comments (which basically repeats what was said in the article) address these issues.
Still, we think that some consensus might be found. Before going to that point, we would like to clarify points raised by our opponents in their last post. 1) For the sake of unbiased discussion, citing one paper showing a lack of VAMP2 expression in astrocytes (Schubert et al.2011) one might mention at least one paper from the large pool showing the opposite (Martineau et al 2013).
More importantly, one should not swap between quantitative and “all-or-none” kind of reasoning to one’s convenience. If we assume that level of astrocytic expression of VAMP2 of tenth of that in neurons is low enough to make VAMP2 non important for function of astrocyte, than we have to assume the existence of certain level of expression below which dnSNARE transgene will not significantly affect neuronal function as compared to astrocytes. OK, it may be not tenth but hundredth fraction, dose not matter.
We thankful to our opponents for bringing up an example of tetanus and botulinum toxins. Even theses deadliest toxins act in dose-dependent manner. Both on the levels of whole organism and single presynaptic terminals, smaller doses of these toxins (as compared to LD50 and IC50) have milder effects. So, it is very likely that effects of dnSNARE expression are dose-dependent (if not to believe in homeopathy, of course).
The same is applicable to the action of doxycycline, which is also dose-dependent. So one could not expect 100% inhibition of transgenes, especially at oral administration of Dox. To answer first part of opponents comment 2), the Figure 1O-R from Halassa et al. shows efficient, but incomplete suppression by Dox, rather than “leaky” EGFP expression. To what extent the same is applicable to Fig.2C of Fujita et al, let the reader to decide. Of course, non-complete suppression by Dox is a downside of tetO/tetA system but this can be easily remedied by comparing On-Dox and Off-Dox data.
2) Theoretically speaking, concern that “neurons express the dnSNARE transgene at all “ may be applicable to any glia-specific transgenic mice. One could not a priori expect an absolute specificity of expression of neuronal and glial genes, the data of Cahoy et al. 2008 are the good illustration. This, rather philosophical, question goes far beyond the current discussion. There is no molecular genetic tool to ensure 100% glial specificity. On practice, one could only expect to obtain a negligible (again, in relative sense) level of neuronal transgene expression and verify the lack of significant impact on neuronal function.
3) Regarding the putative “dramatic and unpredictable “ effects of neuronal dnSNARE expression, the TeNTx and BoNT give a good indication of what to expect. However, dnSNARE mice do not show any notable deficit of motor or respiratory function. On a level of synapses, there was no evidence of any significant decrease (not saying about complete inhibition) of vesicular release of main neurotransmitters (Pascual et al. 2005; Lalo et al. 2014). On contrary, our data show an impairment of signals triggered by activation of Ca2+-signalling selectively in astrocytes (Lalo et al. 2014; Rasooli-Nejad et al. 2014). Let it to the reader to decide, to what extent available functional data support the opponents’ notion that “synaptic transmission may directly be suppressed by dnSNARE expression in neurons “ and that “Even very low levels of expression of dnSNARE in neurons invalidate any conclusion based on this transgenic mouse “.
One might argue that dnSNARE transgene could be expressed only in the certain subset of neurons or in some specific brain region thus strongly affecting some specific function rather than causing general, milder, functional deficit. However, this is unlikely for the supposed basal leakiness of the tet-off system and further experiments would be required to identify such regions/neuronal subsets.
4) Addressing the second half of the point 2) – One can only wonder why, in 2012, already knowing that their results contradict to data presented by that time by several studies, our respected opponents did not contact authors of those publications to request mice from them? Again, one might only wonder why PCR data generated from 2 batches of mice have sample size of n = 3 – 4 (meaning 1-2 tissues per batch) ?
5) Regarding the intrinsic limitations of dnSNARE mice, anyone working with them is aware of fact that EGFP, LacZ, and dnSNARE genes were inserted independently. However, their expression is controlled by the same factors so their expression probabilities depend on the same set of parameters and therefore are not truly independent, from mathematical point of view. The correlation in expression of these transgenes is supported by the co-inheritance. Furthermore, data of Halassa et al. show that 97% of cells expressing the dnSNARE, also express EGFP. We would like to emphasize that the opposite - the presence of true mosaic expression pattern in dnSNARE mice, i.e. existence of number of individual cells expressing dnSNARE and not expressing EGFP and number of EGFP-only cells, has not be shown so far; Fig.3 from Fujita et. al 2014 does not show this either.
Thus, even assuming the leakiness of the “tet-off” system, one might expect probability of EGFP expression to be of the same order of magnitude as that of dnSNARE, this is also agrees with data of Fujita et al. So, in case of absence of EGFP expression in a large population of neurons, the presence of even small fraction of neurons expressing dnSNARE is very unlikely. From mathematical point of view, the probability of certain population of neurons to express only dnSNARE will fall exponentially with the expected size of population.
Finally, one could hardly deny the large difference in the phenotype of the cohort of dnSNARE mice, described by Fujita et al. and the cohort of mice used by other groups. The point of some consensus could be that in some, still unidentified conditions, the tetA/tetO system may suddenly became leaky, causing some level of expression GFAP-driven transgenes dnSNARE, EGFP and lacZ genes in neurons. So, in experiments with dnSNARE mice extra care should be done to verify the lack of neuronal dnSNARE expression. This can be done by showing the absence of surrogate reporters EGFP or lacZ in neuronal populations of interest combined with electrophysiological data showing the lack of deficit of synaptic neurotransmitter release. This could be a good practice for any glia-specific inducible transgene.
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On 2015 Jan 24, Todd Lee commented:
As stated in our paper, we need the data from IMPROVE-IT to better inform us on the use of ezetimibe. However, rather than relying on a conference presentation and press releases we will also need to await the peer-reviewed and sponsor-independent analysis of the IMPROVE-IT trial to judge the quality of the results and evaluate their impact on general practice. Given interim analysis was performed (and the study was subsequently re-sized) any multiple comparisons performed will require expert statistical review.
Furthermore, given no other positive studies exist, it may be prudent to perform an independent individual patient data analysis of all similar studies to better refine or confirm the estimate of effect prior to making any final conclusions from one trial.
The net conclusion of this study, if the presented data is taken at face value, is a number needed to treat (NNT) of 50 over 7 years for the composite outcome. Overall mortality was not reduced. At generic Canadian prices it would cost approximately $58,765 to prevent 1 event over 7 years (Ontario formulary price as of January 2015). However, at US brand name prices of approximately $8.50 per day (Lexicomp 2015) the cost of preventing one composite outcome would be more than $1,000,000.
It is also important to note that IMPROVE-IT was a secondary prevention study (acute event within 10 days) and not primary prevention. In primary prevention, the NNT is likely much higher and the corresponding costs per event prevented would increase proportionately and likely be substantial even at generic prices. In our cohort 6/17 (35%) were receiving ezetimibe for primary prevention.
Whether the drug lowers event rates in the absence of a statin remains unproven and cannot be inferred from this study. Nonetheless, it will be interesting to see the effects on monotherapy uptake given the publicity around this study and also when IMPROVE-IT is ultimately published.
The impact of this study on the uptake of other drugs approved on the basis of LDL as a surrogate marker is also not to be underestimated. The issue of treating to specific LDL targets is currently being debated amongst experts after recent changes to the guidelines. It would be somewhat naive to think that there isn't a substantial market pressure behind bringing back targets to be measured and obtained through additional medications.
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On 2015 Nov 30, John P A Ioannidis commented:
Dear Joshua,
thank you again for your comments. I am worried that you continue to cut and paste to distort my sentences.
- The headline over my text was written by the Nature editors as their introduction to the paper, so perhaps you should blame them and ask them to replace it with "Here follows a horrible paper by Ioannidis". Yet, I think you would still be unfair to blame them, because their headline says "most innovative and influential", not just "most innovative". The terms "influential", "influence", "major influence" pervade my paper multiple times, but you pick one sentence with "innovative" instead, and interpret it entirely out of its context.<br>
- The phrases "the most important" and "very important" are not identical. Very important papers may not necessarily be THE most important. But they are very important - and influential. [As an aside, honestly, this repeated cross-examining quotation-comment style makes me feel as if I am answering the Spanish Inquisition. Am I going to be burnt at the stake now (please!) or there is one more round of torture?]
- We agree we need evidence, more evidence - evidence is good, on everything, including the current NIH funding system, which has practically no evidence that it better than other options, but still distributes tens of billions of dollars per year. Wisely, I am sure.<br>
- "your list contains...". This is not my list. This is the Scopus list. Right or wrong, I preferred not to manipulate it. Your colleagues did manipulate it and did not even share the data on how exactly they manipulated it.
- You continue to use the term "innovative thinker" out of its context. I scanned again carefully my paper and I can't find the word "excellent". In my mind, a student who has authored as first author a paper that got over 1000 citations (and the paper is not wrong/refuted) is already worthy to be given a shot as a principal investigator. If you disagree, what can I say, feel free not to fund him/her. And please don't worry, most of these guys are not funded anyhow currently, many of them even quit science. Hundreds of principal investigators who publish absolutely nothing or publish nothing with any substantial impact get funded again and again. Hurray!<br>
I am afraid it is unlikely there will be more convergence in our views at this point. A million thanks once again, I have learnt a lot from your comments.
John
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On 2015 Jul 15, Raphael Levy commented:
Thanks Harald for commenting on my blog post about SmartFlares / Nanoflares with reference to this paper.
I reproduce the conversation below. I hope it continues and others join in.
Raphael
"Hi everybody, as the correspending author of a Stem Cell paper in which we have used the SmartFlares on different pluripotent cells of human, murine and porcine origin I want to reply to two of the above mentioned questions.
Why do we see a signal at all in the scramble control? I think one cannot expect a negative control which does not produce a fluorescent signal at all. The fluorophore may not be quenched by 100% and may be subject to degradation, especially when applied for a longer time (two days or more). Nevertheless, within 16 to 24 hours after the application of the nanoparticles we see a clear-cut difference of fluorescence intensity when comparing scramble control and gene-specifc Smart Flares. http://www.ncbi.nlm.nih.gov/pubmed/25335772
We believe that this difference is reliable and specific. We have selected freshly reprogrammed murine iPS cells based on their Nanog-specific fluorescence intensity in situ. In downstream experiments we could confirm that only colonies with a high fluorescence intensity expressed higher amounts of endogenous pluripotency factors and showed a superior capacity to differentiate. Therefore, we belive that these functional data strongly support the idea that the fluorescence intensity was indeed correlated to a specific interaction with the Nanog mRNA in these clones.
Why do different cells take up varying amounts of SmartFlares? I think this difference is not surprising as the nanoparticles are engulfed by endocytosis. This process is influenced by the cell type, the differentiation status and the cellular ability to perform phago- and macropinocytosis. Therefore, we think that a uniform uptake rate cannot be expected."
I replied "Hi Harald
Thanks again for commenting here and sorry for the delay in replying. It is interesting that you see some differences but the big question that remains is how could the technology possibly work?
It can only work if the particles escape endosomes, but: 1) there is no reason why they should, 2) this problem is not discussed in the original publication introducing the technology, 3) there is no direct evidence in the literature that it happens, and, 4) all the data we are accumulating indicates that the particles are indeed in vesicular compartments (more on this soon on the open notebook as we have just had our cell electron microscopy results this week).
The images shown in your articles are low mag overviews of many cells and therefore the resolution does not allow to discuss any cellular localization. Do you have any higher resolution images that you could share? Do you have any (direct) evidence and/or proposed mechanism for endosomal escape?
The unequal distribution of uptake (cell to cell variability) is also a big concern. I don鴠believe that it relates to differences between rate of uptake of different cells. Such differences would average over an 18 hour period and they should also be seen in the dextran uptake. A possible interpretation would be some degree of nanoparticle association/aggregation before interaction with the cells (this is to be tested experimentally).
Raphael"
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On 2015 Sep 17, Ghassan El-Baalbaki commented:
authors of this comment are: Loose, T.<sup>1,3</sup> , Ashrah, L.<sup>1,</sup> Romero, M.<sup>1,</sup> Bégin, J.<sup>1</sup> and El-Baalbaki, G.<sup>1,2</sup> Affiliations, Université du Québec À Montréal<sup>1,</sup> McGill University<sup>2,</sup> Université de Nantes<sup>3</sup> .
In this study, the authors examine the efficacy of Acceptance and Commitment Therapy (ACT) in treating partner aggression. After entering into communication with the first author, she confirmed that this study corresponds to her doctoral thesis (Zarling, 2013). We read her thesis in order to gain further knowledge about the published study, and we found two important aspects of the work that need to be brought into light: 1) we find it difficult to conclude that partner aggression was specifically reduced, because of threats to internal validity. 2) There seems to be inaccuracies in their statistical calculations.
The primary objective was to demonstrate that ACT reduces intimate partner aggression better than the placebo control group. The authors strongly suggest that ACT was indeed able to do so. However, several points call this statement into question.
First of all, it is worth noting that partner aggression is never specifically assessed. One may think that the Conflict Tactics Scales-2-Physical Assault Scale (CTS-2) did assess this construct (Straus, Hamby, Boney-McCoy & Sugarman, 1996), but when taking into account the exact content of the administered questionnaire that was figured in her thesis, it can be seen that the instructions were modified in order to include aggression towards “people we care about” (Zarling, 2013, p.132) instead of specifically towards a partner. This modification is not mentioned in the published article. Hence, participants could have hypothetically committed aggressive acts exclusively towards a non-partner, such as a child or a friend. It is thus hard to conclude that aggressive behavior, specifically among couples, decreased as a result of therapy.
Furthermore, after modifying the instructions, one of the items even became incoherent. More specifically, when taking into the modified instructions of the questionnaire, the item stated “When upset or in a disagreement with someone you care about … have you became angry enough to frighten your partner?” (italics added)(Zarling, 2013, p. 132). It seems that this question was destined to ask if the participant became angry enough to frighten someone that they « care about » and not their « partner ». For example, if the participants were (or became) single, they could have interpreted this question as if they were angry enough to frighten someone that is not necessarily their partner. It is unclear how the authors wanted the participants to interpret this item. The way that the construct of partner aggression was assessed calls into question the internal validity of the study.
It remains questionable why the authors neglected to assess attrition of couples during the study. Over the course of the study, it is possible that aggressive behavior decreased more in the ACT group as a result of more couples breaking up in this treatment condition than in the placebo control group. Even if the authors carried out both completer analysis and intent to treat analysis and the results did not differ on measured variables, the attrition of couples was not measured. Hence, it is impossible to know if the groups differed on partner attrition. It remains possible that participants continued to aggress former partners, but again this cannot be asserted simply because it was not measured. Assessing partner attrition would have helped neutralize a pertinent threat to internal validity. Hence, internal validity was limited by not taking into account partner attrition.
Lastly, it is worth bringing up that the first author and two other investigators co-led all administered interventions (p. 201). Even if the authors state this in their article, after looking at the detailed explanation of the recruitment process of investigators, this choice does not seem to be justified. It seems that the first author was able to recruit investigators at no extra cost and it is questionable as to why she did not recruit three instead of two, thus avoiding a potential threat to internal validity. The explanation provided in her thesis, but not the article, also states that all the manipulation checks were carried out by the first author and supervised by the second and third authors (Zarling, 2013, p.61). Because of the implication of the authors in the experimental procedure, the results are potentially attributable to the experimenter expectancy effect. This is another threat to internal validity that evokes the tendency for researchers to unintentionally bias the results of their investigations in accord with their hypotheses. In taking into account the previously stated points, it seems difficult to conclude that this study shows that ACT specifically reduces partner aggression better than a placebo control group.
On another note, the statistical validity of the study can be questioned:
Throughout the results section of the paper (pp. 205–207), the authors report many beta values (β) for intercepts and slopes. If these are indeed beta values, they should vary between approximately 1 and -1 (Cohen, Cohen, West & Aiken, 2002). However in many cases, reported values are outside of this range. For example the authors state “The ACT participants also reported significantly less psychological aggression, β = 2.05, SE = 0.71, t(97) = 8.33, p < .001, and physical aggression, β = 2.21, SE = 0.65, t(97) = 8.19, p < .001, at the 6-month follow-up assessment” (p. 8). This leads us to think that the authors are actually reporting non-standardized coefficients (B) because B values can vary outside of this range. However, if this is the case, then the t values reported become incoherent. t values should equal B/(2SE) (we retained the value of 2 after rounding up from 1.96 which corresponds to 95% of a normal distribution (Christensen, 1986)), but reported t values do not correspond to this calculation. For example, let’s take another look at the previous citation and assume that it actually refers to B values. According to our calculations, t = B/(2SE) = 2.05/(2*0.71)=1.44, but the authors report that t = 8.33, p < .001. More simply stated,if the authors are indeed reporting β values, then many of the β values seem to be impossible (outside of the ± 1 range), but if they are reporting B values, the t values seem to be impossible according to our calculations. We were wondering how these seemingly paradoxical results could be explained.
In conclusion, even if this research topic is of great interest, two main points should to be taken into account. First of all, it is hard to state that ACT is an effective treatment to reduce partner aggression because 1) partner aggression was never specifically assessed 2) partner attrition was not measured 3) of potential bias due to the experimenter expectancy effect. Secondly, it is hard to draw conclusions from the statistics figured in the study because 1) if β values were indeed being reported, then they lie outside of the ± 1 range and 2) if B values were actually reported, then the t values become incoherent.
References
Christensen, H. B. (1986). La statistique: démarche pédagogique programmée. Boucherville: Gaëtan Morin.
Cohen, J., Cohen P., West, S. G. et Aiken, L. S. (2002). Applied multiple regression/correlation analysis for the behavioral sciences. New York: Routledge.
Straus, M. A., Hamby, S. L., Boney-McCoy, S., & Sugarman, D. B. (1996). The revised conflict tactics scales (CTS2): Development and preliminary psychometric data. Journal of Family Issues, 17, 283–316.
Zarling, A. (2013). A preliminary trial of ACT skills training for aggressive behavior. University of Iowa.
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On 2014 Oct 18, David W Brandes, MS, MD, FAAN commented:
I am very happy to see more published information about this topic. I have been speaking professionally abut this topic for 10 years and it is becoming increasingly recognized as to it's importance in the management of MS patients. This article confirms the often unrecognized frequency of this issue. When MS patients say they "are tired all the time," we need to think about the details. Physical fatigue, cognitive fatigue, psychological fatigue (depression) and sleepiness may all be part of this complaint.
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On 2014 Aug 04, Paul Brookes commented:
This paper addresses a very important point... namely, one of the proposed mechanisms by which ischemic preconditioning (IPC) is thought to bring about cardioprotection. It has been hypothesized that increased leakiness of the mitochondrial membrane to protons may lead to a lowering of ROS generation. We provided some evidence to support increased H+ leak in IPC in 2006 Nadtochiy SM, 2006. Unfortunately, it's not immediately clear to me exactly how the authors measured H+ leak in this study, and also whether their ROS measurements were performed correctly.
First proton leak: The normal way this is determined is to make simultaneous measurements of membrane potential and respiration in a single chamber equipped with an oxygen electrode and another electrode sensitive to a lipophilic cation such as TPP+. The authors are to be commended on their choice to use a TPP+ electrode, which instantly makes this paper more quantitative than others using qualitative fluorescent probes such as TMRE. They measured membrane potential (as reported in Figure 3) using succinate as a substrate for complex II, with rotenone to inhibit complex I. All good so far. However, normally oligomycin is added to inhibit the ATP synthase as a potential source of leak. In addition nigericin is added to equilibrate K+/H+ and thus ensure the potential is a measure of protonmotive force. As such, the potential measured here was not in a true state 4 condition which is typically required for quantitation of proton leak.
After describing membrane potential measurements, the methods section describes respiration and H+ leak methodology. It appears oligomycin was added this time (good!), but then something very odd happens... it is stated that "H+ leak was measured as the state 2 respiration rate required to maintain membrane potential at -150mV". Nowhere is it stated how that value of 150mV was arrived at. Normally, when doing these measurements, you set the mitochondria in state 4 (succinate, rotenone, oligomycin, nigericin), and then titrate the activity of the respiratory chain with an inhibitor such as malonate. Step-wise titration then gives you a series of membrane potential and respiration traces, a curve, from which the leak rate at any given potential can be read off. The question is, if such curves were made, how were they made (no mention of malonate anywhere), and why aren't they shown in the paper? The scary alternative explanation may be that they "measured" leak by imposing the 150mV membrane potential by titrating in uncoupler. This is incorrect - you can't add something that changes the leak as a way of measuring the leak. The other odd thing is that the average baseline membrane potential in the IR group barely above 150mV, so some replicates in that group must have had a potential value below 150mV to begin with. How did they authors get those mito's UP to 150mV for the leak measurement? Overall, it would be a whole lot better if they just showed the full leak curves.
What about ROS? The problems here are two-fold. First it appears that SOD was not added to the incubations to scavenge any stray superoxide and turn it into H2O2 for the assay to pick up. Second, the calibration of the assay was performed incorrectly. It is stated in the methods that the signal was calibrated by "adding known concentrations of H2O2 to buffer solution containing horseradish peroxidase and Amplex-Red" The problem is, it is necessary to calibrate in the presence of mitochondria, so the signal you measure with the calibrating H2O2 is under the same condition as the measurement itself. The way this is commonly done is to just add a bolus of H2O2 at the end of each run. This has the advantage of making every run internally calibrated, which cuts down on noise (this is a very noisy assay). The outcome here is a bit odd... the values of H2O2 generation are in the range of 10-40 nM/min/mg protein. Ignoring the odd units (rates of things should be expressed in moles not Molar), let's assume they meant to write nmols/min/mg - that would put their rates about 1500-fold greater than typical for these conditions (e.g.Chen Q, 2003).
So, TL/DR - good ideas, but more info' is needed on the proton leak method, and the ROS numbers are just wild. Also, lest anyone think I'm attacking this work because I happen to be one of the people who originally proposed proton leak --> lower ROS --> protection in IR injury, that's not the case. In-fact, my lab' is now pursuing a completely different downstream signaling mechanism, as a mediator of the protective effects of mitochondrial uncoupling, so if the results of this paper are true, my life just got a whole lot easier! I just want to be sure before I start citing it.
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On 2014 Aug 06, Xudong Fu commented:
Thanks for your comments. It is really interesting. I hope I could explain why I don't think alpha-ketoglutarate works as an antioxidant to extend lifespan.
It has been shown that α-ketoglutarate is an antioxidant. However, antioxidants are not necessarily able to extend lifespan. Actually, the relationship between ROS and lifespan has not been established. Increase of ROS may contribute to lifespan extention potenially through downstream defensim activation and overexpression of antioxidant enzyme is not able to extend lifespan in mice (http://www.sciencedirect.com/science/article/pii/S0092867413006454, http://onlinelibrary.wiley.com/doi/10.1111/j.1474-9726.2008.00449.x/full).
Our paper discovers that α-ketoglutarate can bind and inhibit ATP synthase and extend lifespan in C. elegans. The inhibition of ATP synthase is actually likely to generate more ROS. It has been shown that oligomycin, a known ATP synthase inhibitor, could induce ROS in vivo. In our hand, we also find that α-ketoglutarate could induce ROS (by DCFDA dye measurement) both in C. elegans and cells. That suggest α-ketoglutarate is unlikely to increase lifespan simply through antioxidant function. It's more likely α-KG regulates lifespan through induction of ROS instead. We actually have explained why we don't think ROS plays a major role in the life extension effect for α-ketoglutarate; see Supplementary Information (http://www.nature.com/nature/journal/v510/n7505/extref/nature13264-s1.pdf). Briefly speaking, although α-ketoglutarate could induce ROS, additional antioxidants does not decrease the lifespan extension effect of α-KG in our hands. In addition, ROS has been suggested to activate TOR but we observed α-ketoglutarate decrease TOR.
In terms of the dosage we used, it has been known that α-KG is not highly membrane permeable. To solve this issue, we made octyl α-KG, an ester form of α-KG which is more membrane permeable. After octyl α-KG goes into the membrane, it gets hydrolyzed and releases free α-KG. Most of the assays in Fig. 2 were done with octyl α-ketoglutarate instead of original α-KG. That's the main reason we don't need to use 8mM dose for Fig. 2 assays. We also tried octyl α-KG in lifespan assays (see Extended Data Table 2). It only required micromolar scale of octyl α-KG instead of millimolar for us to observe the lifespan extension. In addition, after treatment of 400 uM of octyl α-KG on cells or after treatment of 8mM α-KG on C. elegans, the in vivo concentration of α-kG increased comparably around 50-100%. That suggest 50-100% increase of endogenous α-KG could inhibit ATP synthase and extend lifespan, nonetheless the different forms or concentration of α-KG we used, consolidating our hypothesis that α-KG extend lifespan through direct ATP synthase inhibition. Also, because the endogenous increase of α-KG is only 50-100%, this concentration does not seem to be in line with the concentration suitable for non-enzymatic reaction.
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On 2015 Apr 24, BSH Cancer Screening, Help-Seeking and Prevention Journal Club commented:
The HBRC journal club read Scherer et al’s paper with interest. While flu vaccination is not the focus of our work, using metaphors as a manipulation to increase the likelihood of a behaviour and the methods used to test the efficacy of doing so, resonated with our research team. Most of the group were unfamiliar with the metaphor literature and found the introduction to provide a useful summary of the field. The authors present a discussion of the role of risk perceptions and affect, but a more detailed discussion of how the two interact and their complexities might have provided a truer representation of the field.
The group liked that the authors attempt to measure whether participants were likely to move beyond intention (measuring participants’ desire to receive a reminder email to get a flu vaccination), without having to measure behaviour (which is difficult to do objectively). However, contrary to the authors, the finding that individuals who occasionally get a flu vaccine were more likely to request an email reminder was unsurprising to us because individuals who always get a flu vaccination seemingly do not need reminding. A further strength of the paper is that non-emotive metaphors were considered (the flu as a weed), as this helped dispel the suggestion that the effect was due to vividity or violence (as might be the case with metaphors such as ‘beast’ and ‘riot’). The group wondered if a virus could also be considered to be a metaphor, given its use in computing. Additionally, it may have been of interest if the vaccination itself was also part of the metaphor, for example the flu virus being described as a ‘weed’ and the flu vaccine as ‘weed killer’. In Hauser DJ, 2015 using congruent metaphors to describe an illness and the measure to prevent the illness increased behavioural intentions compared to just using a metaphor to describe the illness.
While metaphors may increase the vividness of the flu and encourage individuals to engage, the group were concerned about how use of metaphors to manipulate behaviour may not be congruent with informed decision making, instead being considered coercive. We disagreed with the authors suggestion that metaphors might have a use in decision aids, which we believe have a role in helping individuals make informed decisions and not swaying their opinion. We suggested that metaphors might be useful when the aim is to increase individuals’ understanding, rather than increasing intentions to engage in a behaviour. It may also be important to consider the unintended consequences of using metaphors, for example in the cancer field (the focus of our work), describing cancer as a battle may lead to suggestions that people who do not survive the disease did not fight hard enough. However, we acknowledge that metaphors are used ubiquitously in the media, which is difficult to control.
The group felt that flu vaccination was a complex example to choose to conduct these studies. Flu is a fairly common illness, which might result in participants having an accurate estimate of their risk of contracting the illness or how serious it is. This might explain why the manipulation did not affect the mediators in the main analysis. Individuals are likely to have existing beliefs about vaccination (for example, beliefs about side effects, effectiveness) and the benefits of vaccination might not always be obvious (the individual does not contract the flu - a non event and herd immunity benefiting the population). It would have been helpful to have been informed about the flu vaccination recommendations in the USA where the study was conducted. Cultural differences in how the flu is appraised, treated and prevented between countries might alter the effect of metaphors. For example, in the group’s opinion, the metaphor ‘beast’ was an exaggerated conceptualisation of the flu and felt removed from the actual consequences of the virus.
Study 3 was perceived by the group to be the most useful study of the paper as it used a validated measure of affect and a larger sample than Study 1. The ecological validity of studies 2 and 3 could have been increased if Study 1 had been a ‘think aloud’ study, whereby the authors could have gained a justification for the mediators of flu vaccination that were tested. The group thought that a strength of the studies is that the authors did consider the possible mediators of any effect of the metaphor. Other mediators that could have been considered include attitudes and a measurement of arousal (engagement). A ‘think aloud’ study might also help to ensure that metaphors are used appropriately, for example in Hauser DJ, 2015, use of an enemy metaphor reduced intentions for self-limiting cancer prevention behaviours (such as stopping smoking or limiting alcohol intake). The group also wondered how novel the ‘novel’ metaphors used in the studies actually were, something that pilot work could have investigated.
The group thought it was interesting that the findings were not wholly consistent across the studies reported and considered that this could have been a product of differences in the sample. The authors do not describe whether participants were randomised to each condition, and no baseline measurements were reported, both of these factors leave readers unclear about whether the sample was similar across each of the studies. It would also have been helpful to have a justification for the sample size chosen for each of the studies.
Scherer et al. present a novel paper, which has provided readers with examples of how to measure the impact of using metaphors to increase intentions to receive a flu vaccination. Future work in this field should consider conducting pilot work to ensure the topic, manipulation and measures used are relevant to the population of interest. We caution readers to consider the unintended consequences of using metaphors to manipulate behaviour, including concern about the ethical implications this might have.
Conflicts of interest We report no conflict of interests and note that the comments produced by the group are collective and not the opinion of any one individual.
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On 2014 Mar 24, Karen Woolley commented:
FINALLY...more attention is being paid to PRACTICAL issues about data sharing!
Well done to Wilhelm, Oster, and Shoulson for reminding us that it takes resources (financial and nonfinancial) to share data. We should also remember that it takes resources (financial and nonfinancial) to publish data. This issue seems to have been lost in the hand-wringing taking place over low and slow publication rates.
A robust systematic review, presented at the 2013 Peer Review Congress (organised by JAMA and the BMJ) identified “lack of time” as the main reason why researchers don’t write up manuscripts.<sup>1</sup> Clearly, many researchers need writing support (ie, from legitimate, ethical, highly trained and qualified professional medical writers; NOT ghostwriters). Similar to Wilhelm et al., we outlined the need to consider the cost issue if we want to enhance publication speed and quality.<sup>2</sup> We think our paper struck a chord - it was among the top 5 most downloaded papers from Current Medical Research & Opinion that year.
Professional medical writers are trained to help make complex data understandable to different target audiences (eg, researchers, regulators, patients) and could, therefore, help address another critical point made by Wilhelm et al., “Standardization costs for data-sharing models include the additional effort required to share, beyond what is required of any high-quality clinical research, because it takes considerably more effort to organize and make data understandable to others.”
Wilhelm et al. conclude that “Understanding and planning for the costs [for data sharing] at the outset of research can help realize the full potential of data sharing.” The same sentence could apply to publications ie, understanding and planning for the costs of manuscript writing at the outset of research can help realise the full potential of peer-reviewed publications.
Authors and affiliations Karen L. Woolley PhD CMPP,a Art Gertel MS,b Cindy Hamilton PharmD,c Adam Jacobs PhD,d Jackie Marchington PhD CMPPe (Global Alliance of Publication Professionals; www.gappteam.org) a. Division Lead. ProScribe – Envision Pharma Group; Adjunct Professor, University of the Sunshine Coast, Australia. b. VP, Regulatory and Medical Affairs, TFS, Inc.. USA; Senior Research Fellow, CIRS. c. Assistant Clinical Professor, Virginia Commonwealth University School of Pharmacy; Principal, Hamilton House, USA. d. Director, Dianthus Medical Limited, UK. e. Director of Scientific Operations, Caudex Medical, UK.
Disclosures All authors declare that: (1) all authors have or do provide ethical medical writing services to academic, biotechnology, or pharmaceutical clients; (2) KW’s husband is also an employee of ProScribe – Envision Pharma Group; all other authors’ spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (3) all authors are active in national and international not-for-profit associations that encourage ethical medical writing practices. No external sponsors were involved in this study and no external funding was used.
References 1. Scherer RW, Ugarte-Gil C. Authors’ reasons for unpublished research presented at biomedical conferences: A systematic review. http://www.peerreviewcongress.org/abstracts_2013.html#1 Accessed 27 February 2014. 2. Woolley KL, Gertel A, Hamilton C, Jacobs A, Snyder G (GAPP). Poor compliance with reporting research results – we know it’s a problem…how do we fix it? Curr Med Res Opin 2012;28:1857-1860.
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On 2014 Oct 18, Pavel Baranov commented:
What is the difference between Open Reading Frame (ORF) and Coding Sequence (CDS)?
Thank you for the reply. I think the disagreement lies in our understanding of what Open Reading Frame is.
A simple and effective definition of ORF is a sequence of codons not interrupted with stop codons: nucleotide sequence is open for reading in one of the three (for RNA) or six (dsRNA) frames. ORF is an abstract notion, it can be found in any sequence. Both protein-codng and non-coding sequences have ORFs.
Coding Sequence (CDS) is the part of RNA that encodes protein. CDS often, but not always (exceptions are ribosomal frameshifting, stop codon readthrough, etc.), is located within a single ORF. A single ORF may contain more than one Coding Region if, for example, translation begins at different start codons within the same ORF.
From your reply I presume that you suggest to define ORF as a sequence of codons from start to stop (like CDS). But the problem with this detention is that it is unclear what should we consider as a start of ORF. AUG? But not all AUGs are starts and not all starts are AUGs. Also there are no starts in non-coding RNAs, but there are ORFs in non-coding sequences.
Besides if we use this definition, all eukaryotic mRNAs coding for multiple protein isoforms would need to be described as bi- or even polycistronic.
I hope that this discussion brings some clarity to the terminology used or at least it draws attention to a potential confusion when terms such as ORF, CDS and cistron are not explicitly defined.
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On 2014 Jun 18, Gauthier Bouche commented:
We would like to thank the authors for carrying out this very important update and for emphasizing that patients with locally advanced rectal cancer should be informed of the lack of consensus about adjuvant chemotherapy after preoperative chemoradiotherapy. As the authors point out in their discussion, ’the control of occult distant disease is becoming a major objective in treatment strategies’. They indicate upfront chemotherapy as one relevant option being tested in a large randomised trial (PRODIGE 23). Our international collaborative group interested in ‘financial orphan therapies’ - i.e. therapies with high clinical but no or low commercial value - has identified over the years several therapeutic options that we think could prevent distant metastasis in patients with locally advanced rectal cancer. We would like to list three promising strategies supported by clinical and biological evidence. These strategies carry a low toxicity risk, are low cost and are easy to administer.
Cimetidine is an H2-receptor antagonist which has been used for decades as an oral drug in the prevention and treatment of gastro-duodenal ulcers. Cimetidine has demonstrated a strong anticancer effect (Kubecova M, 2011) that is unlikely to be explained by one single mechanism. Amongst other things, cimetidine inhibits cancer cell adhesion via E-selectin inhibition (Matsumoto S, 2002), increases the antigen-presenting capacity of dendritic cells (Kubota T, 2002), increases lymphocyte infiltration in tumours (Lin CY, 2004) and reduces accumulation of myeloid-derived suppressive cells (Zheng Y, 2013), which may all contribute to the clinical findings in colorectal cancer patients. A 2012 Cochrane Meta-Analysis reviewed the five randomised trials performed in colorectal cancer patients and concluded that ‘cimetidine appears to confer a survival benefit when given as an adjunct to curative surgical resection of colorectal cancers’ (Deva S, 2012). The main unanswered question is duration of treatment. The randomized trial currently ongoing in 120 colorectal cancer patients in New-Zealand and Australia (ACTRN12609000769280) which aims to look at the effect of perioperative cimetidine should answer this question. Recruitment in this trial has been completed and 45% of all patients have a primary rectal cancer (http://meetinglibrary.asco.org/content/122801-143).
Polysaccharide-K (PSK) is isolated and purified from the cultured mycelium of the Basidiomycete Coriolus versicolor. It was first approved as an oral anticancer drug in Japan in 1976 under the name of Krestin® and its use has been restricted to colorectal, gastric and small-cell lung cancer after re-evaluation by the Japanese authority in 1989 (Maehara Y, 2012, Fujiwara Y, 1999). Several randomized trials of various quality have been performed over the past four decades in Japan which overall indicate a benefit in colorectal cancer patients (Maehara Y, 2012). The drug is now available as a generic in Japan (Fujiwara Y, 1999). The most critical question is whether similar outcomes would be found in a non-Japanese population. Since this therapy has shown excellent safety and is already commercially available in Japan, this question could be easily tested in randomized trials. Mechanistically and according to the wealth of literature available from Japanese researchers, PSK seems to have multiple mechanisms of action, from direct anticancer activity to immune-mediated effects (Maehara Y, 2012). Obviously, any project or trial outside of Japan should involve Japanese clinicians and researchers experienced with PSK.
Ketorolac is a Non-Steroidal Anti-Inflammatory Drug (NSAID) approved in the EU and in the USA and available for injection in the management of postoperative pain. In 2010, Forget et al. found in a retrospective study that breast cancer patients undergoing mastectomy who had received one single injection of ketorolac during surgery had a 63% reduction in the risk of recurrence compared to patients who did not, even after adjustment for known confounders (Forget P, 2010). This association was confirmed in patients receiving either ketorolac or diclofenac and undergoing breast-conserving surgery (Forget P, 2014), as well as in patients undergoing lung cancer surgery (Forget P, 2013). The work from Ben Eliyahu’s group provides a biological rationale for this, even though Ben Eliyahu used etodolac in combination with propranolol and the design of the mice experiments is different from the human observations (Benish M, 2008). Retrospective data in colorectal cancer patients should be available soon from the group of Patrice Forget (personal communication) and will hopefully further support this hypothesis. The potential benefit of perioperative administration of ketorolac will have to be balanced against a potential risk of anastomotic leakage. A meta-analysis of randomized trials indicates a non-significant doubling of the risk (2.4% in patients not receiving NSAID vs. 5.1% receiving NSAID within 48 hours of surgery Burton TP, 2013), but such increase has not been observed when only one single dose of NSAID was administered. This will however need to be taken into consideration when designing a trial of perioperative ketorolac in colorectal cancer patients.
We can deduce from the Bosset et al. article that there is an early peak of recurrence in the first two years, as more than 50% of the DFS events occurred during this period. This is in line with data from DeMicheli for breast (Demicheli R, 2010) and lung (Demicheli R, 2012) cancer and is another argument to target the perioperative period with drugs such as NSAID or cimetidine to prevent recurrence (Demicheli R, 2008).
There are other options which could be considered. However, the strategies we propose have a common theme. Our goal is to address the fact that the perioperative period is one that is characterized by a systemic immune and pro-angiogenic milieu that is found in a typical wound healing response. Such a response is characterized by a post-operative surge of cytokines and growth factors into the systemic circulation that may awaken dormant micrometastases, thus accounting for the early recurrence pattern seen following surgery for many types of cancer (Retsky M, 2013). Thus short-term perioperative treatments aimed at countering such a response could have long-term beneficial consequences. Finally, these treatment options represent low-hanging fruits which, if their efficacy were to be proven in trials, could be rapidly implemented in practice in most places in the world with minimal toxicity and at a reasonable cost. We sincerely hope to see others supporting this type of research.
Gauthier Bouche, Anticancer Fund, Strombeek-Bever, Belgium
Pan Pantziarka, Anticancer Fund, Strombeek-Bever, Belgium & The George Pantziarka TP53 Trust, London, UK
Lydie Meheus, Anticancer Fund, Strombeek-Bever, Belgium
Patrice Forget, Department of Anesthesiology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
Vidula Sukhatme, GlobalCures, Inc; Newton MA 02459, USA
Vikas P. Sukhatme, GlobalCures, Inc; Newton MA 02459, USA & Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
The authors declare that they have no competing interests.
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On 2014 Jul 09, Mathias Wellmann commented:
Comment regarding Kukkonen et al. Treatment of non-traumatic rotator cuff tears. A RANDOMISED CONTROLLED TRIAL WITH ONE-YEAR CLINICAL RESULTS, Bone Joint J 2014;96-B:75–81. PMID: 24395315
Dear Authors,
we read the study with great interest und discussed the clinical implications. We think the authors did a great job respecting formal aspects (prospectively randomized design, equivalent cohort size, homogeneous patient distribution). However, there are a few aspects of the study which are potentially misleading:
The title of the study is misleading or to general at best. A more precise title would be: Treatment of small, well compensated non-traumatic supraspinatus tendon tears. We think a study title should be as clear as possible and should especially answer the question: What issue was studied? The study of Kukkonen et al. exclusively investigated patients with small (<10mm) supraspinatus tendon tears, which were well compensated regarding range of motion (full range of motion, inclusion criteria). In its present form the title of the study may lead to a transfer of the results to patients with decompensated full-thickness tears of the supraspinatus tendon. Such transfer is not valid and should be prevented using a more precise study title.
All patients with an passive external rotation <30° and an elevation <120° were excluded from the study and the limitation of elevation and external rotation was defined as stiffness. However, a loss of elevation <120° is not a sufficient criterion to define shoulder stiffness. An adequate examination would have quantified passive glenohumeral abduction and external rotation (external rotation in comparison to the contralateral unaffected side). Further, the percentage of patients excluded because of shoulder stiffness should be indicated, since this is not a very common combination in patients with atraumatic rotator cuff tears. In the given form there is a risk that the study design systematically excludes patients with restricted range of motion caused by loss of strength and pain. This is a basic issue, since these are the typical patients, in which we think about rotator cuff refixation.
The type of supraspinatus-tears for the patients, that were included in the study should be clearly defined (full thickness versus partial thickness tears). The authors use the term „supraspinatus tendon tear comprising <75% of the tendon insertion and documented with MRI“. Thereby it is unclear, if partial articular und bursal sided tears involving <75% of the tendon substance were also included in the study. In the results section the authors indicate the sagittal diameter of the tears treated by surgery. Does that mean, that all tears were full-thickness tears?
It is unclear, if any of the patients had been treated by physiotherapy previous to the inclusion, or if this was an exclusion criterion as well. How did the authors deal with patients, that were randomized to be treated by surgery but did not agree to a surgical intervention.
The authors did not perform a follow up MRI or even sonography to determine the rerupture rate of the rotator cuff repairs. This would have been a substantial information estimating the clinical success of rotator cuff repair. If further follow up investigations are planned in the study design, we strongly recommend to perform MRI scans.
The Constant Score may not be the most helpful score with regard to outcome discrimination for a patient population with „ full range of motion“, since it strongly estimates range of motion (40 points) compared to pain (15 points) and the level of daily actvities (20 points). For such patients more detailed patient reported outcomes (PROs) should be beneficial.
We recommend to revise the marked aspects to reach the highest possible scientific impact for this publication.
Mathias Wellmann on behalf of the Shoulder committee of the AGA - Society for Arthroscopy and Joint Surgery
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On 2014 Jan 24, Tom Kindlon commented:
The validity of using subjective outcome measures as primary outcomes is questionable in such a trial
Crawley and colleagues suggest dropping school attendance as a primary outcome from the full study, and replacing it with self-report outcomes "such as the SF-36 or the Chalder Fatigue Scale" and using "school attendance as a secondary outcome"(1). And indeed, this is what they have done with the full study which has two primary outcome measures: "Chalder Fatigue Scale at 6 months" and "SF 36 physical function short form at 6 months"(2). I question the wisdom of using self-report measures as primary outcomes for such a trial.
The authors do not give much information about the details of the Lightning Process (they do mention it is "developed from osteopathy, life coaching and Neuro-linguistic programming (NLP))" but here are some descriptions from other sources (individuals who have undertaken a course) (note these are not descriptions from participants from the trial itself):
(a) "It felt very naughty but I whispered to one of the woman (sic) sitting next to me 'how are you, is this working for you?'. She was reluctant to answer, to say anything but that she was doing well would be to go against the process because that is a negative thought. It was pointless asking really. Still I wanted it to work, but I was starting to worry about the fact that I was not only not feeling any better the effort of doing the course, not getting my normal rest was making me feel worse. But these were negative thoughts. I started to ruthlessly suppress them like I had been shown." (3)
(b) “They tell you that you're not allowed to say that you're ill anymore or that you have any symptoms. They force you to ignore the symptoms because they say that the symptoms don't really exist. They force you to do activities even though it's making you really ill, but you're not allowed to say so.” (4)
Another, more thorough, description can be found on the Skeptic's Dictionary website(5).
I have seen many similar descriptions to these in discussions in many private fora. Here's one example: "So the first step in the process is to recognise when you’re in THE PIT. Maybe sometimes or all the time. It’s important to recognise what you say to yourself as you go into the pit. For example “I’m feeling really ill this morning”, “if I do this, then I’ll get exhausted”, “last time I did this I got really ill for days”, “I can never eat this” etc. This takes some practise but we were assured that you always say something in your head as you go into the pit. As soon as you spot one of your “pit” phrases you want to STOP yourself right away. So imagine you’re on the mat and you start to say “I feel really ill today”. Before you get to the end of this phrase you will interrupt with a very firm, loud “STOP” (yes, talk out loud to yourself!) and jump into the STOP position as described above. So you jump outside the mat, to your left. Now you’re here you have interrupted your bad thought patterns."
In essence when one is doing the lightning process, both during the three days training and after, you are to declare yourself well. You are not to say (or think) you have symptoms and you are not to say (or think) you have limitations. In other words, patients are 'trained' to dismiss and deny their symptoms and illness. Patients are instructed not to “do” ME or CFS anymore. In such a scenario, subjective reports from the patient are no longer reliable. Hence the need for objective measures in such trials.
To a lesser extent, it can also be argued that subjective measures are not ideal for all participants in this trial, including the control group. With graded activity-oriented therapies, which all the participants undertake (1), there may be response bias (6). This was seen in a review of three Dutch trials of graded activity-oriented cognitive behaviour therapy (CBT) for CFS. While the CBT participants reported improvements in fatigue (and also SF-36 physical functioning although that was not measured in all of the trials), no improvements in objectively measured activity were reported over the control group(7). Similarly a mediation analysis showed changes in physical activity were not related to changes in fatigue. A similar effect with CBT could be in PACE Trial, the largest such trial in the CFS field(8).
Although participants who had undergone CBT reported improvements in scores on both the Chalder Fatigue Scale and SF 36 physical function subscale, no improvements were reported in the six minute walking distance compared to the group who had undergone no additional individual therapy (all participants had specialist medical care). Similarly, CBT did not significantly reduce employment losses, overall service costs, welfare benefits or other financial payments(9).
Objective measures of physical activity are one type of objective measurement that could be employed. This could be used not just to measure the total quantity of activity but also to check the intensity of activity as people with ME/CFS may perform lower levels of more intensive activity(10). Tests of neuropsychological performance could also be used, given the impairments that have previously been reported(11). If necessary, a webpage could be created that could be accessed remotely.
One particular problem with the 0-33 scoring method for the Chalder fatigue scale is that patients can give unusually low, or artificially good, scores.
The scale consists of 11 questions. For each question (e.g. "Do you have less strength in your muscles?"), patients have to say whether they have the symptom: "Less than usual" (score of 0); "No more than usual" (score of 1); "More than usual" (score of 2) or “Much more than usual” (score of 3). So healthy people should score around 11 and indeed in the only population study I can recall that gave data for a healthy (no disease/current health problem) group, the mean was 11.2 (12).
However, some unusual scoring is possible. This was seen in a multiple sclerosis trial, of a similar CBT intervention to the graded activity-oriented CBT used in CFS (13). Participants in the CBT leg of the trial entered with a Chalder fatigue scale score of mean (sd): 20.94 (4.25). Two months after therapy, the mean (sd) was 7.90 (4.34) i.e. this groups suffering from multiple sclerosis had a much better score than one sees in healthy people!
Such averages could also hide non-responders or, possibly more seriously, people who deteriorated, depending on how the data was analysed. For example, if two participant deteriorated and ended up with a Chalder fatigue scale scores of 32, but 8 others had an average score of 2, this would give an average score of 8, again giving the impression that this group had less fatigue than healthy people. This issue of supranormal scoring with likert scoring (0-3) can be dealt with by utilising the commonly used bimodal scoring method for the Chalder fatigue scale. However, both it and likert scoring suffer from ceiling effects in CFS populations so other scales are likely preferable (14,15). If the Chalder fatigue scale is used, the original developers of the scale suggested, based on their analyses, that "it would probably be more useful to have two scores, one for physical fatigue and one for mental fatigue"(16).
(Message has reached word limit - references are reply)
Competing interests: I am the Assistant Chairperson and Information Officer for the Irish ME/CFS Association. All my work for the Association is voluntary.
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On 2014 May 22, L. Norton commented:
Nice work. Background is certainly an issue in ChIP-Seq studies and I think one way to deal with this is to examine gene expression of the proposed targets following knock-down of the transcription factor. Although this is not a perfect solution, after doing these experiments it becomes apparent that very few ChIP-Seq binding events are 'functionally significant' in a way that we expect (i.e. effect transcription). As a side note, I wonder if you or anyone else has examined the impact of sonication vs. MNase digestion on this phenomenon?
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On 2014 Mar 21, Jacob Puliyel commented:
Williams and colleagues have described assessment of AEFI employing the algorithm described by Halsey < PMID: 22507656>.
I have posted two very detailed comments to an article by Tozzi Tozzi AE, 2013 which discusses the same subject of the revised WHO Classification of AEFI. I will not repeat the points I have made there but it may be viewed here.
As this is a matter of patient safety I think it is important that the experts who understand the new scheme must explain why the revision was needed and that it will not miss opportunities of picking up new signals. The question is whether the new scheme would have picked up and flagged the signal of adverse-effects like the RotaShield-reactions, had the scheme been in use in 1999. The purpose of this posting is to invite the learned authors of this article on causality assessment to respond to the issues raised in the postings to the Tozzi article and I propose to flesh out those concerns a little further in the context of the article in Pediatrics by Williams and colleagues.
1) Williams and colleagues Williams SE, 2013 suggest that the first step in the general approach to evaluating serious AEFI is to establish a clear diagnosis using Brighton Collaboration case definitions.
The second step is to consider known biological mechanisms.
Neither of these would have been evident when the intussusceptions signal was picked up by the old scheme (and the vaccine was withdrawn expeditiously preventing unnecessary distress to thousands of babies). Even today although a case definition has been developed for ‘intussusceptions’, the biological mechanism is not clearly defined and so the second step described by Williams et al cannot be completed.
It was reported recently that Pentavalent vaccine (DPT co-administered with measles vaccine (MV) and yellow fever (YF) vaccine) is associated with increased mortality compared to MV + YF alone Fisker AB, 2014. It is pertinent to mention that the biological mechanisms involved are not understood.
Neither is the biological mechanism for increased female mortality in recipients of the high-titer Edmonston-Zagreb vaccine known, although this was first noticed 2 decades ago. < PMID: 8237989>, Aaby P, 1993.
2) It will be instructive to look at how the new algorithm has failed to flag up the deaths following Pentavalent vaccine used in Asia (DPT + Hib + Hepatitis B) and as a result, numerous children continue to be exposed to the risks of this vaccine.
The glossary of the User Manual for the [Revised WHO classification]( who.int/vaccinesafety/publications/aevimanual.pdf) suggests ways and means to rule out a causal association. It defines causal association as a cause-and-effect relationship between the causative factor and a disease with no other factor intervening in the process.
There have been many deaths following use of this Pentavalent vaccine in Sri Lanka. The committee WHO vaccine safety examined 19 deaths in Sri Lanka, 14 of them between 2010 and 2012. In six of the 19, a congenital heart disease was reported.
Does preexisting congenital heart disease rule out a causal association between the vaccine and the deaths? Under this definition the 6 deaths in children with heart disease were not causally related to the vaccination.
The older Advisory Committee on Causality Assessment Collet JP, 2000 looked at the problem more logically and holistically. For example it noted that elderly persons with concomitant or preceding chronic cardiac failure can develop cardiac decompensation after influenza vaccination due to a vaccine-caused elevation in temperature or from stress from a local reaction at the site of vaccinating. The vaccine is considered to have contributed to cardiac failure in this specific situation. It is obvious that with the older method of assessment of AEFI, caution would have been exercised when administering influenza vaccine to persons with preceding chronic cardiac failure, to avoid decompensation.
The deaths in children with heart disease following administration of Pentavalent vaccine could well be due to decompensation. The Pentavalent vaccine must be used with caution in the presence of an underlying heart condition albeit asymptomatic. However detection of asymptomatic heart disease prior to vaccination in developing countries is impractical where the vaccine is administered by health workers who are barely literate. Is it prudent to use the vaccine under these circumstances given the findings of the Sri Lanka investigation? The new system disregards this real danger.
3) Step 2 Checklist 4 of the revised [WHO classification for causality assessment]( who.int/vaccinesafety/publications/aevimanual.pdf) asks to check if the event can occur independently of vaccination (background rate). Thus it seems that until the deaths from vaccine AEFI are frequent enough as to increase the age specific mortality-rate in a statistically significant manner, they are to be ignored.
The question of what background rate to use is not addressed specifically and this can further confound objective assessment of the AEFI. The Pentavalent vaccine in Asia is administered after 6 weeks of age. Would the local post-neonatal infant mortality rate (PN IMR) in the community before introduction of the vaccine be the comparator?
Most of this post-neonatal IMR is made of babies who are very sick with pneumonia, diarrhea, sepsis, meningitis etc. The fact that the AEFI babies were brought by the mother for routine immunization suggests that the child was not sick and the mother did not consider the child was likely to die in the next day or two. The comparator must really be the SIDS rate in the locality for babies of a comparable age.
Deaths in Bhutan were investigated and local newspapers reported on the various official explanations. It was argued that the deaths could have been due to encephalitis although there was little evidence for it. Officials explained that the encephalitis death rate in the years after the vaccine was introduced (even after adding AEFI deaths) had not increase significantly. This was sufficient grounds to accept the ‘coincidental encephalitis’ theory. One cheeky health official however pointed out that there were no cases of meningo-encephalitis reported among children below one year, in the eight months when Pentavalent vaccine was suspended in Bhutan.
4) Another factor related to the deaths following Pentavalent vaccine is that the vast majority have occurred after the first dose and fewer after the second dose. A random event or coincidental SIDS cannot explain these deaths. However the new algorithm does not take this important factor into consideration.
For all these reasons it would appear that the new algorithm is not a comprehensive means to assess serious adverse events. Its use will delay withdrawal of vaccines that result in serious AEFI and in the end it will erode confidence in the entire immunization programme and those who administer it.
Can I suggest that we need to go back use older scheme namely Brighton Classification of AEFI till we find a better method to assess AEFI.
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On 2014 Aug 11, Dr. Priyanka. M Jadhav commented:
Ayurveda: science beyond scepticism and snake oil
Priyanka M. Jadhav, Research Scientist
Maharashtra University of Health Sciences
Comment on: Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial
Sir, This is the age when the concept of remote surgery does not surprise us, but we are not prepared to accept a concept that has existed and survived for centuries—the science of Ayurveda. I read with great interest the study published by Chopra et al. and am excited that the New Millennium Indian Technology Leadership Initiative (NIMTLI) project set up with an interdisciplinary approach is evaluating traditional and Ayurvedic drugs in clinical trials for treatment of osteoarthritis[1]. It is interesting to see how modern medicine approach is being used to study the effect of an Ayurvedic medicine assessed by a series of experiments [2–4]. The acceptance of Ayurveda or any other traditional system of medicine in western medicine is low; however, what causes frustration are the allegations and misinformation being promoted.
Recently, a a letter was published in which the author termed Ayurveda as quackery.[5] Patients and the next generation who aspire to find a cure and career in this age-old science find such information as very misleading and confusing. On the other hand, many other journals are documenting the reports on the study of these drugs.
The National Center for Complementary and Alternative Medicine clearly states the lack of randomized controlled clinical trial for complementary and alternative medicines and a need to build evidence-based datab to assess the plausibility of claims[6].
As an Ayurvedic practitioner, I welcome such suggestions and efforts, which are more than mere dismissal of age-old science. Although the current research and published papers concentrate on the extracts of plants, the point of holistic treatment is lost. As many scientists use extracts, the pressure of using purified extracts in studies is very high. Any researcher who proposes to work on a whole medicinal plant not only faces technical difficulties but also pressure from the scientific community, which again steers them to use purified extracts. Negative results of many experiments are not even published.
NMITLI arthritis project is one such attempt to translate the language of traditional medicine in a way that the western world can understand. In doing so, the scientists involved are those who are experts in their field and have done their best to generate data from in vitro and human studies. Moreover, one can also argue that Ayurveda treats a patient not only by medicine but also by other methods such as application of oil, hot fermentation, purgation, etc., which varies for each patient depending on their prakruti or constitution.[7] If one aims to study these medicines, a novel and innovative approach or a fresh perspective is needed when designing a suitable trial. [8]
More such studies as the one done by Chopra et al. should be done. Such studies will focus on chronic and infectious diseases, which are of grave concern not only for the developing or resource-poor countries but also for the developed world too. These medicines may form a good alternative, if not a substitute, for modern medicine that has mild to severe adverse effects particularly for chronic diseases. In a way, this study may be a base to prove to the funding agencies and other organizations that natural products can be just as effective as modern ones.
Some very important issues to be addressed are whether we are prepared to accept a concept riddled with prejudice or embrace one used by billions for their good for centuries.
References
1 Chopra A, Saluja M, Tillu G et al. Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial. Rheumatology 2013. doi: 10.1093/rheumatology/kes414. First published online: January 30, 2013.
2 Chopra A, Saluja M, Tillu G et al. Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: a Government of India NMITLI arthritis project. J Ayurveda Integr Med 2012;3:38-44.
3 Chopra A, Saluja M, Tillu G et al. A randomized controlled exploratory evaluation of standardized ayurvedic formulations in symptomatic osteoarthritis knees: a government of India NMITLI project. eCAM 2011;2011:724291.
4 Sumantran VN, Kulkarni A, Chandwaskar R et al. Chondroprotective potential of fruit extracts of Phyllanthus emblica in osteoarthritis. Evidence-based complementary and alternative medicine : eCAM 2008;5:329-35.
5 O'Cathail S, Stebbing J. Ayurveda: alternative or complementary? Lancet Oncol 2012;13:865.
6 Briggs JP. NIH. Turning discovery into health? Available from: http://nccam.nih.gov/about/offices/od/2011-06.htm (17 April 2013, date last accessed).
7 Dieppe P, Marsden D. Managing arthritis: the need to think about whole systems. Rheumatology 2013.doi: 10.1093/rheumatology/ket127 First published online: March 7, 2013.
8 Patwardhan B. Ayurveda GCP guidelines: need for freedom from RCT ascendancy in favor of whole system approach. J Ayurveda Integr Med 2011;2:1-4.
Conflict of Interest: None declared
Published July 9, 2013 http://rheumatology.oxfordjournals.org/content/52/8/1408.long/reply#rheumatology_el_105
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On 2014 May 06, Madhusudana Girija Sanal commented:
Dr. Norman is picturing the great progress in education as a result of the information distribution revolution as if it is an ‘unavoidable evil’! Probably, many of his generation expresses high inertia, still consider, 'physical' universities, libraries, books, lecture halls etc. very much essential! I understand their nostalgia! You know what this means for humanity? Rich countries such as USA hold only a small fraction of the world’s population. Through virtual universities more and more people across the world, irrespective of rich and poor, would be able to attend the best schools and courses. They would be able to take the same exams and get ranked along with the most privileged, rich or intelligent. This would be great! This is 'new' justice! (Although I believe “Justice is ‘man made’ or artificial”). All we want is better tools to evaluate human intellectual qualities, online. I do not think face to face lectures will be better than online recorded, interactive lectures, may be multidimensional (3D-4D-5D) lectures by several professors of the learner’s choice. Lectures will be ranked and paid by based on their quality by student communities and not by bureaucrats or by administrators and politicians. This system is great especially when I consider the advantages! On demand, personalized lectures would be "ready-made" for commonly observed (student) personality traits -say there are 100 personality subtypes and intellectual levels! Custom lectures are available for them all because there are much more people to teach online-lectures need not be real time. You can learn from a "personality" who matches your rare personality, perhaps, one who lived 10 years back. His lectures had to wait for ten years for a student like you! Is not this a very exciting possibility? However, I do agree that face to face lectures can be more individualized and beneficial (for the rich, because they only have money to ‘buy’ good teachers!) Nevertheless, I do not think there is a huge benefit for extreme personalization except for exceptional children who are extremely out-of-the-box in a positive or negative way. It may be, however, noted that overall poor but brilliant students have a better opportunity to come out and stand before the world. This global free learning system will benefit specially those brilliant minds in less privileged countries. Do Dr. Norman has any evidence to support his statements in the editorial? I do not know what Dr. Norman will write if tomorrow we find a new technology which allows direct transmission of knowledge to brains! Then what will happen? Think! Everyone will have equal opportunity to accumulate the same amount of information if he or she wants. Now who will win this game? Those who have money? Probably not! Those fractions of the society who are blessed with right genome, epigenome and the best neural connections!
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On 2015 Apr 02, Marcus Munafò commented:
Flegal and colleagues suggest that being overweight may decrease risk of all-cause mortality, and being slightly obese confers no increased risk compared to being of normal weight [1]. We think these conclusions are misleading and may give a detrimental public health message, particularly given the publicity they attracted.
Despite the authors’ suggestion that there is “little support for the suggestion that smoking and pre-existing illness are important causes of bias”, these factors are not consistently controlled for within the contributing studies [1]. It has been demonstrated in two large prospective studies that the increased risk of death from being overweight or obese can be masked when smoking is not adequately controlled for, and when sufficient initial years of follow up are not excluded [2]. Smoking is associated with both lower body mass index (BMI) and increased risk of death, while underlying illness can lower BMI prior to death. Furthermore, it is widely appreciated that conventional statistical approaches to “control” for such factors are inadequate. Support for a positive causal effect of BMI on mortality comes from studies less subject to the biases associated with BMI measured in later life because they used BMI in adolescence or offspring BMI as the exposure [3, 4]. These measures are suitable proxies since they are strongly associated with an individual’s BMI in middle age but are not substantially affected by reverse causality and are less confounded by smoking. Higher BMI in adolescence was associated with greater risk of all-cause mortality in middle age in a study of over 200,000 individuals [3]. Stronger inferred associations were observed with offspring BMI and all-cause and cardiovascular mortality than with own BMI, suggesting that positive associations of BMI and mortality may in fact be underestimated in conventional observational studies [4]. In addition, this study demonstrated that the commonly observed inverse association between BMI and death from respiratory and other diseases may also be due to such biases.
Given the importance of the public health messages regarding “healthy” weight, we feel that further research is needed in this area using innovative research methods to overcome potential biases; further conventional observational studies will simply recapitulate the biases inherent in all such investigations. One such approach would be Mendelian randomisation, using obesity-related genetic variants, such as those in FTO. Mendelian randomisation methods, when applied correctly, are free from confounding by environmental factors and are not affected by reverse causality [5].
Marcus Munafò, Amy Taylor and George Davey Smith
- Flegal, K.M., et al., Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA, 2013. 309(1): p. 71-82.
- Lawlor, D.A., et al., Reverse causality and confounding and the associations of overweight and obesity with mortality. Obesity (Silver Spring), 2006. 14(12): p. 2294-304.
- Bjorge, T., et al., Body mass index in adolescence in relation to cause-specific mortality: a follow-up of 230,000 Norwegian adolescents. Am J Epidemiol, 2008. 168(1): p. 30-7.
- Davey Smith, G., et al., The association between BMI and mortality using offspring BMI as an indicator of own BMI: large intergenerational mortality study. BMJ, 2009. 339: p. b5043.
- Davey Smith, G. and S. Ebrahim, 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol, 2003. 32(1): p. 1-22.
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On 2014 May 05, Madhusudana Girija Sanal commented:
Creativity in biology-reply to Bruce Alberts
Bruce Alberts, describes biology as 'not at all an easy science' (1). This entirely depends on the definitions of boundaries! Biology is more factual and visual (and hence ‘easy’ for majority) than physics and mathematics. However, biology attains the same degree of difficulty at its interface with these subjects were mathematics or physics is applied to answer biological questions.This relative ease may be one of the reasons we find more students graduating in biology than other basic sciences (2). Creativity in the generation of new ideas and concepts is the essence of science. The current 'reward-recognition' system which just counts the papers is not recognizing this fact. The current trend is to evaluate scientists on the basis of the number of publications and their impact factors rather than their impact on the growth of science and the betterment of the society. This has resulted in a ‘publish or perish’ situation leading to an increase in junk and fraudulent publications (2). The cracking of the central dogma in biology or the invention of PCR brought new concepts in biology. Personalized medicine, designer molecules and proteins and regenerative medicine have huge potential. However,currently the society is wasting its resources in premature translational research and personalized medicine which are growth arrested in infancy, awaiting major developments in technology to overcome the bottlenecks (3). Any significant leap in biology needs a major leap in chemistry, physics and mathematics. These subjects provide not only technology and tools but also concepts for the growth of biology. So funding and research in other fields need be encouraged for the development of biology (2).
Life Sciences-where ‘workers’ take a lead over thinkers!
The number of publications in biology is proportional to the amount of ‘work done’ rather than “adventure of ideas”. This is causing many problems. For example this results in the dissolution of the boundaries between a scientist, a technician and a robot (2). The number of papers and the journals in which they are published often becomes a matter of chance, available workforce, availability of funds and collaborations which in turn depends on politics, influence and umpteen other factors decreasing the overall importance of intellect on scientific publication. It is difficult to assess individual contributions of the authors-who contributed more for the concept and who did most of the (technician) work-from a research article. Needless to say that who contributed towards the development of the concept should be given more credit. But this is rarely practiced (2).
The future of Biology
We are still taking the same cereals, pulses, milk and meat, which existed thousands of years before! We have yet not created any new plant or animal! Currently in biology, we move in a top to bottom fashion i.e.; explore the existing biological systems and reveal the science behind them and copy it, re-engineer it, according to our need. For example, find out a gene, find its importance, function, the protein coded, structure, interactions etc But I feel biology mature enough to think moving the other way i.e.; design a gene according to our need-plan its structure function, interactions etc according to our need design it. If I extend this view we should be able to engineer and produce totally new proteins or organisms rather than building or modifying from an existing (natural) platform (2).
Other major advancements will be in creating brain-computer interfaces and computer assisted thinking, electronic immortalization of personalities (individuals), planned generation of citizens of varying functions and capabilities for the better service of the society etc. For all this to happen the limiting step is the development of basic sciences which could then be easily translated to appropriate technologies.
1) Alberts B.Creativity at the interface. Science. 2012 Apr 13;336(6078):131. 2) Sanal MG Where are we going in science? Publish and perish! Current Science 2006 3) Maher B. Nature.Tissue engineering: How to build a heart. 2013 Jul 4;499(7456):20-2
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On 2014 Jan 12, Brett Snodgrass commented:
Dear Authors,
Thank you very much for the excellent publication and acknowledging that the connections between the coronary arteries and left ventricle were not probably not veins.
These connections may represent the vessels of Wearn, which appear unusually prominent.
An applicable ICD9 code might be 746.85, coronary artery anomaly, as it may meet the clinical criteria for the definition of fistulae.
Referring to these arterial connections as Thebesian veins has caused me much confusion when I was trying to understand the simple relationship of pulmonary atresia with intact ventricular septum and the coronary arteriopathy seen in PAIVS. With the growth of social media, and electronic data storage, I think that we may now be able to address the diffuse distribution of ambiguous or misleading nomenclature that fills as least half of related publications.
Dr. Paul Lurie's plea for collaboration in this regard has motivated me to take several steps in an effort to try to help produce accurate, simple, precise anatomic nomenclature and include:
I collaborated with Elsevier to help get the article by Wearn et al. changed to open-access. http://bit.ly/JTWearn
I obtained the original article (through ArtRieve http://www.artrieve.com/) written by Thebesius and uploaded the first digital copy. http://bit.ly/Thebesius
I published or wrote in the American Journal of Cardiology, Cardiovascular Pathology, Twitter, Facebook, Google Plus, and directly E-mailed several authors that were publishing related content.
I have posted numerous PubMed Commons comments. I regret that they may not always be helpful to every user, but I echo Dr. Lurie’s plea for collaboration in this regard. The PubMed Commons commentary is a welcome means with significant potential to vastly improve the peer review process.
My aim is that researchers in the future will probably not need to read more than 30 articles before they realize that myocardial sinusoids indeed exist, they were defined by Wearn, and that Thebesian veins are not arteries.
Please see
My opinion is that accurate anatomic terminology is a basic principle underlying good medical science, and I ask others to consider whether the aforementioned definitions are appropriate. If this comment is not helpful, please let me know how it might be improved.
Comments and suggestions are welcome.
Thank you very much.
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On 2015 Dec 06, Mark Bolland commented:
This comment provides background information to an earlier comment.
We were interested in why different meta-analyses of vitamin D supplements came to different conclusions, and noticed that different meta-analyses used different data from this trial. We identified several errors/inconsistencies in the text and emailed the lead author requesting clarification about the data in March 2014. He responded that the data in the Tables were correct. We replied that there were inconsistencies within the Tables as well and asked for clarification, but he did not respond.
Therefore in April 2014, we contacted the editor of Osteoporosis International advising the editor of the inconsistencies and requested that they be corrected. We felt this is particularly important as it is a highly cited, influential trial reporting benefits of vitamin D supplements on falls, and the inconsistencies occur in the treatment group numbers and the primary and secondary outcomes, so have a major bearing of the interpretation of the trial results. Our primary concern was/is to use the correct data for the trial in meta-analyses. In May 2014, the editor passed on an extract of the lead author’s response and indicated that an erratum would be published. However, we felt the lead author’s response was inadequate because it left a number of uncorrected inconsistencies/errors in the text. We pointed this out to the editor. We are not sure what action the editor took, but no erratum was published. We followed up with 2 further emails to the editor over the next year, and in April 2015, the editor advised that it seemed unlikely that an erratum would be forthcoming.
Therefore, we requested the permission to summarize the issues in a very brief letter. The editor agreed and a short letter summarizing the six errors/inconsistencies in the article was published (Osteoporos Int 2015;26:2713 Bolland MJ, 2015) with a response from the author (Osteoporos Int. 2015;26:2715-6 Pfeifer M, 2015). Unfortunately, in his response the author chose to correct only 2 of the errors identified and introduced a further inconsistency.
In a further letter to the editor, we therefore highlighted the remaining errors/inconsistencies and the consequence of using different possible data combinations from this trial for meta-analyses. The editor indicated that the issues we raised were important but probably irresolvable and offered to publish the letter in Archives of Osteoporosis. We indicated that our preference was that the data were corrected in the original publication rather than our letter being published. We think it quite straightforward to make the simple necessary corrections to two tables and a couple of sentences of text. We feel it is essential that the corrections occur as the errors are in the most important data from the trial: the treatment group numbers and the primary outcome data for falls. The editor considered the issue further and then published our letter (Arch Osteoporos. 2015;10:43 Bolland MJ, 2015) along with a response from the author (Arch Osteoporos. 2015;10:42 Pfeifer M, 2015).
In this second response, the author has still not corrected the identified errors, so, because of the inconsistencies/errors in the data, it is not possible to be sure how many women were in each randomized treatment group, how many women had a fall during the trial, how many total falls occurred in each treatment group, or what is the breakdown of participants by numbers of falls (no falls, 1 fall, 2 falls, etc).
Therefore, we think that the study should be excluded from meta-analyses and systematic reviews and its results viewed with caution until consistent data are provided by the authors with some explanation as to how the errors/inconsistencies occurred.
Mark Bolland, Andrew Grey. University of Auckland
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On 2014 Jan 04, Tom Kindlon commented:
The dropping of actometers as an outcome measure and other points relating to the outcome measures being used
(I'm posting this e-letter/comment from 2008 here for the same reason as the first e-letter below)
In their reply to my comments, Peter White and colleagues say they are using [i]"several objective outcome measures"[/i] [1]. If they think these tests are useful as objective outcome measures, why is at least one of them not being used as a primary outcome measure rather than the current situation where there are only two subjective outcome measures being used.
I have already made some points on the outcome measures but another one is that the bimodal Chalder Fatigue Scale hardly seems a very good outcome measure for a "CFS/ME" trial where there is likely going to be so many maximum or near maximum scoring initially[2]
Also, there are so many (14) secondary outcome measures in this study, along with so many (18) predictor variables, that it seems unlikely all the different methods of looking at the secondary outcome measures can be explored in the final published paper, given authors are encouraged not to make papers too long (especially journals that have paper editions). The protocol itself is 20 pages long when all the different aspects of it are listed! At least some of the information will need to be re-iterated in the final paper.
It is of course important to take the burden on participants into account when deciding what outcome measures to use. However I find the following point very strange: "Although we originally planned to use actigraphy as an outcome measure, as well as a baseline measure, we decided that a test that required participants to wear an actometer around their ankle for a week was too great a burden at the end of the trial." Firstly they clearly don't find it that great a burden that they drop it altogether as it is being used on patients before the start. If they feel it was that big of a burden, it should probably have been dropped altogether.
Of course, other studies in the area have used measuring over a similar or longer period. For example, Bazelmans [3] used an actometer over 14 days, Black [4] used actigraphy over 14 days, Sisto[5] used actigraphy over 7 days, Vercoulen[6] used an actometer over 12 days and Van der Werf [7] used an actometer for 12 days.
Also if one wants to reduce the burden on patients, why not take out one or both of the exercise tests instead. As the clinicians in the study would know, post-exertional symptoms are part of the condition.
For example, Nijs[8] performed a gentle walking exercise on patients where they walked on average 558m(+/-340) (range: 120-1620) at a speed of 0.9m/s (+/-0.2) (range: 0.6-1.1). This resulted in a statistically significant (p<0.05) worsening of scores in the following areas when comparing pre-exercise, post-exercise and 24 hour post-exercise scores using ANOVA: VAS fatigue, VAS musculoskeletal pain, VAS sore throat, SF-36 bodily pain and SF-36 general health percention. 14 out of 24 subjects experienced a clinically meaningful change (worsening) in bodily pain (i.e. a minimum change of the SF-36 bodily pain subscale score of at least 10).
Those results are similar to another study[9] which involved the acute effects of 10 discontinuous 3-minute exercise bouts on a treadmill in 10 CFS patients. In between exercise bouts, there was a 3-minute recovery period between exercise bouts. The participants walked at a comfortable walking pace self-selected by the subjects. On average, the subjects walked at a speed of 0.71+/-0.20 m/s. Some patients reported experiencing headaches, leg pain, fatigue or sore throats.
In another study, Lapp [10] (not to be confused with Clapp[9]) reported on the effects of 31 patients to his practice who were asked to monitor their symptoms three weeks before to 12 days after a maximal exercise test. 74% of the patients experienced worsening fatigue and 26% stayed the same. None improved. The average relapse lasted 8.82 days although 22% were still in relapse when the study ended at 12 days. There were similar changes with exercise in lymph pain, depression, abdominal pain, sleep quality, joint and muscle pain and sore throat.
These are just a small selection of the studies which show patients experience an exacerbation of their symptoms following exercise testing. So these are the sorts of symptoms the patients may expect following the exercise. This reminds me that there seems to be a lot of concentration on measuring fatigue in this study - there are many other symptoms that are part of "CFS/ME".If they had used actometers instead of, say, doing one of the exercise tests, the response to the exercise could have been followed to see how long and how severe an effect the exercise had on the patient. Or they could have dropped both the exercise tests altogether.
As well as "subjective" findings following exercise testing, there have also been objective findings. Arnold et al[11] found excessive intracellular acidoss of skeletal muscles with exercise. Jammes[12] found an increase of damaging oxidative stress following exercise testing. So patients could not just endure temporary sysptom but possibly also longer-term harm from exercise testing. There are numerous other exercise abnormalities.As the clinicians involved in the study probably hear from patients, one of the frustrating things about ME or CFS is that people don't realise the payback that they can have from doing things. This would have been an opportunity to investigate this as part of the study. But now the effort patients will put in and the payback they will feel in some ways is being wasted as the effects won't be measured.
Anyway, to repeat again, given the authors familiarity with the literature, I find it strange that they would decide using an actometer would be worse than putting patients through two exercise tests.
I also find it surprising that in a study part-funded by the Department of Work and Pensions (DWP) that the objective outcome measures (not involving questionnaires) are all once-off exercise tests. It has been established that patients need to be able to do things on several days during a week before they can be passed fit for work. I have mentioned using actometers following exercise tests after an exercise test above; of course, actometers wouldn't have to be used at that time but also during a "normal week".
Proponents of pacing methods including APT would say that there is a "ceiling of activity" that patients can't go above without experiencing a worsening of symptoms. Black[13] has found evidence of this. Proponents of CBT or GET for "CFS/ME" would suggest that patients can gradually just increase how much activity they can do. Actometers would also have tested the hypothesis. As it stands, the study will not give us information on this as just because patients answer questionnaires saying they're improved (which could simply be because they think they're better) or improve their exercise results (which might simply be because they're willing to push themselves more) doesn't prove that they don't have an activity ceiling above which they experience disabling symptoms (esp. when, as in this study, there is no follow-up period following the exercise testing). This is the real "heart" of the issue but given the current design, the question won't be answered.
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On 2015 Dec 28, Lydia Maniatis commented:
Part 1. I have criticized Purves and colleagues' various iterations of the “wholly empirical” account of visual perception in various comments on PubMed Commons and on PubPeer. Here, I want to present a more comprehensive and organized critique, focussing on a study that has served as a centerpiece of these accounts. I think it is important to clarify the fact that the story is profoundly inadequate at both the conceptual and the methodological levels, and fails to meet fundamental criteria of empirical science (logical consistency and testability). Such criticism (which is not welcome in the published literature) is important, because if “anything goes” in published research at even the most elite journals, then this literature cannot help to construct the conceptual infrastructure necessary for progress in the visual sciences.
Conceptual problems LACK OF THEORETICAL MOTIVATION The hypothesis that the authors claim to have tested is effectively conjured out of thin air, subsequent to an exposition that is inaccurate, inadequate, and incoherent.
The phenomenon to be explained is inadequately described. We are told, first, that the luminance of a “visual target” elicits a “brightness” percept that can vary according to “context.”
The term brightness, here, is being used to refer to the impression of white-gray-black that a surface may elicit (and which is currently referred to by researchers as its “lightness.”) However, surfaces do not necessarily, or even usually, elicit a unitary percept; they often produce the impression of double layers, e.g. a shadow overlying a solid surface. Both the shadow and the surface have a perceptual valence, a “brightness.” Indeed, it is under conditions where one “target” appears to lie within the confines of a double layer, and the other does not, that the most extreme apparent differences between equiluminant targets arise.
The logic is simple: If a surface appears to lie under a shadow, then it will appear lighter than an equiluminant target that appears to lie outside of the shadow, because a target that emits the same amount of light under a lower illumination as one under stronger illumination must have a higher light-reflecting tendency (and this is what the visual system labels using the white-gray-black code.). The phenomenon and logic of double layers is not even intimated at by these Yang and Purves (2004); rather, the impression created is that the relationship between “brightnesses” under different “contexts” is not in the least understood or even amenable to rational analysis. (In addition, the achromatic conditions being considered are rare or even non-existent in natural, daytime conditions; but the more complex phenomenon of chromatic contrast is not mentioned.)
After this casual attempt to convince readers that vision science is completely in the dark on the subject of “brightness,” the authors assert that “A growing body of evidence has shown that the visual system uses the statistics of stimulus features in natural environments to generate visual percepts of the physical world.” No empirical studies are cited or described to clarify or support this rather opaque assertion. The only citation is of a book containing, not evidence, but “models” of brain function. The authors go on to state that “if so, the visual system must incorporate these statistics as a central feature of processing relevant to brightness and other visual qualia.” (It should be noted that the terms “statistics” and “features” here contain no concrete information. The authors could be counting the stones on Brighton beach.)
Even if we gave the authors the latitude to define “statistics” and “features” any way they wish, the following sentence would still come out of the blue: “Accordingly, we propose that the perceived brightness elicited by the luminance of a target in any given context is based on the value of the target luminance in the probability distribution function of the possible values that co-occur with that contextual luminance experienced during evolution. In particular, whenever the target luminance in a given context corresponds to a higher value in the probability distribution function of the possible luminance values in that context, the brightness of the target will be greater than the brightness elicited by the same luminance in contexts in which that luminance has a lower value in the probability distribution function.”
This frequency-percept correlation, in combination with the claim that it has come about on the basis of evolution by natural selection, is the working hypothesis. It is a pure guess; it does not follow naturally from anything that has come before, nor, for that matter, from the principles of natural selection (see below). It is, frankly, bizarre. If it could be corroborated, it would be a result in need of an explanation. As it is, it has not been corroborated, or even tested, nor is it amenable to testing (see below).
THE HYPOTHESIS The hypothesis offered is said to “explain” a narrow set of lightness demonstrations. Each consists of two displays, both containing a surface of luminance x; despite being equiluminant, these surfaces differ in their appearance, one appearing lighter than the other.
The claim is as follows: The visual system has evolved to represent as lighter those surfaces that appear more frequently in one “context” than in another. Thus, in each display, the surface that appears lighter must have been encountered more often in that particular “context” during the course of evolution. It is because seeing the higher-frequency target/context combination as lighter was “optimal” this situation arose. More specifically, it is because the response “lighter” to a target in one “context” and “darker” to a target in another context, and so on for contexts in-between, has had, over evolutionary time, positive adaptive effects, that these percepts have become instantiated in the visual process.
DO ORGANISMS TRACK ABSOLUTE AND RELATIVE LIGHT INTENSITY OVER MOMENTS, HOURS, DAYS, EONS, AT ALL POINTS IN THE RETINAL IMAGE, AND WHEN DID THEY STOP DOING THIS? The hypothesis would appear to presuppose that organisms can discriminate between, and keep track of, the absolute luminances of various “targets” in various “contexts,” as they have been encountered with every glance, of every individual (or at least the ancestors of every individual), at every point in the visual image, every moment, hour, day, across the evolutionary trajectory of the species. There is no suggestion as to how these absolute luminances might be tracked, even “in effect.” Not only is it difficult to imagine what mechanism (other than a miracle) might allow such (species-wide) data collection (or its equivalent) to arise, it runs contrary to the physiology of the visual system, in which inhibitory mechanisms ensure that relative, not absolute, luminance information, is coded even at the lowest levels of the nervous system. Furthermore, given that lightness perception does not change across an individual's lifetime, nor depend on their particular visual experience, it would seem that this process of statistical accumulation must have stopped at some point during our evolution. So we have to ask, when do the authors suppose this (impossible) process to have stopped, why did it stop, and what were the relevant environments at that time and previously? (The logical assumption that the authors suppose the process has, in fact, stopped is reinforced when they refer to “instantiated” rather than developing “statistical structures.”)
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europepmc.org europepmc.org
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On 2016 Jul 23, Lydia Maniatis commented:
This article is illustrative of the degradation of theory and practice in vision science. The article is not new (but compare with, e.g. Graham, 2011), but many of its assumptions and the style of argument - tolerance for layers upon layers of uncorroborated assumptions and inadequate, ad hoc models - are still very current and underpin a broad swath of contemporary (arguably pseudoscientific) activity. Below are quotes from the article and my comments.
The abstract: "Light adaptation has been studied using both aperiodic and periodic stimuli. Two well-documented phenomena are described: the background-onset effect (from an aperiodic-stimulus tradition) and high-temporal-frequency linearity (from the periodic-stimulus tradition). These phenomena have been explained within two different theoretical frameworks. Here we briefly review those frameworks. We then show that the models developed to predict the phenomenon from one tradition cannot predict the phenomenon from the other tradition, but that the models from the two traditions can be merged into a class of models that predicts both phenomena."
Comment: One wonders whether the merger was ultimately successful, and whether falsifying phenomena from yet other traditions could be merged with these two, to expand the ever-expanding ad hoc circle of tradition.
Note that the piecemeal "merger" philosophy expressed by Graham and Hood seems to preclude falsification. Falsifying phenomena from another "tradition" simply lead to the summing of individual ad hoc models into a compound ad hoc model, and so on. The complexity but not the information content of the models will thus increase. (This will also likely produce internal inconsistencies that not be noticed because they will not be looked for.) The question of whether these models correspond with the facts that they are supposedly trying to explain never really arises.
All this can be garnered from the abstract: If anything, the text is even worse.
"None of the parts of the merged models, however, is necessarily correct in detail. Many modifications or substitutes would clearly work just as well at this qualitative level. …Also, one could certainly expand the model to include more parts. …Similarly, the initial gain-controlling process might be composed of several processes having somewhat different properties"
Comment: The models are arbitrary, ad hoc, incomplete on their own terms, and there is no rational criterion for choosing among an infinite number of alternatives.
"No attempt was made to fine-tune either model to predict all the details in any one set of psychophysical data…much less in all the other psychophysical results that such a model might bear on…To attempt such a project in the future might be worthwhile...particularly if the experimental results were all collected on the same subjects..."
Comment: In other words, because the models are ad hoc they may only explain the results to which they were tailored. It may (or may not??) be worth checking to see whether this is the case. I.e. testing models for correspondence with the phenomena is optional. The effects in question are too fragile and too little understood to be tested across subjects with varying methods.
"The more vaguely-stated possibility suggested by this observation, however, is that any decision rule of the kind considered here may be in principle inadequate for the suprathreshold-discrimination case. It may be impossible to explain suprathreshold discriminations without more explicit modeling of higher-level of higher-level visual processes than is necessary to explain detection (where detection is a discrimination between a stimulus and a neutral stimulus.)... Thus a simple decision rule may be suitable in the detection case simply because all the higher-level processes are reduced to such simple action THAT THEY BECOME TRANSPARENT." [caps mine].
Comment: The idea that there are certain experimental conditions in which the conscious percept consists in the reading off of the activity of "low-level" neurons (as though there was a direct qualitative correspondence between neural firing and seeing, e.g., a blank screen!) is patently absurd and has been criticized in depth and from different angles by Teller (1984).
Pretending that we take it seriously, we could refute it by noting that the presumably simplest of all stimuli - a white surface free of any imperfections - produces the perception of a three-dimensional fog. Other experiments have also shown that organizational processes are engaged even at threshold conditions, and that, indeed, they influence thresholds.
The "transparency theory" is repeated by Graham (2011) in an article in Vision Research: "It is as if the near-threshold experiments made all higher levels of visual processing transparent, therefore allowing the properties of the low-level analyzers to be seen."
This casually proposed "transparency" theory of near-threshold stimulation is apparently the basis of the widespread belief in spatial frequency channels and the extraordinary elaboration of associated assumptions. Without the transparency theory, it is not clear that even cherry-picked evidence can support this popular field of research. (If you've ever wondered at the widespread use of "Gabor patches" in vision research, this is the root cause - they are considered elemental due to the transparency theory-supported low-level neuron spatial frequency sensitivity hypothesis. I suspect many of the people using then don't even know why).
Graham and Hood (1992) also go into a little finer detail about the putative basis of transparency: " In the suprathreshold discrimination case, the observer is trying to discriminate between two sets of neural responses…both of which sets contain many non-baseline responses. In the detection case…the observer is simply trying to detect some non-baseline responses in either set (since that is the set most likely to be the non-blank stimulus). Thus a simple decision rule may be suitable in the detection case simply because all the higher-level processes are reduced to such simple action that they become transparent."
Comment: The suggestion that investigators are managing to set their low-level visual neurons at baseline at the start of experiments also seems implausible. I certainly don't think this has been explicitly discussed from the point of view of method. "However, at this moment in time, we seem to be able to explain background onset with a subtractive process…Thus, we can just leave as a marker for the future – should troubles in fully explaining the data arise – the possibility that the background-onset effect in particular (and perhaps all the results) will not be explained in detail without including more about higher-level visual processing."
Comment: Translation: We'll accept our ad hoc hypo thesis for now, but it's probably wrong. But we'll worry about that later, if and when anyone makes trouble by bothering with actual tests. Because there's always a (zero) chance that it will be corroborated.
Finally, the article also provides a good example of misleading use of references: "Quantal noise exists in the visual stimulus, as is well known (see Pelli for a current discussion.)"
Comment: From Pelli, 1990: "It will be important to test the model…For gratings in dynamic white noise, this [model] prediction has been confirmed by Pelli (1981), disconfirmed by Kersten (1984) and reconfirmed by Thomas (1985). More work is needed." But we don't need to wait for evidence to firmly believe in "quantal noise."
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pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
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On 2017 Feb 10, David Attwell commented:
The answers to Dr Brette’s new points are as follows.
(1a) Ohmic vs Goldman dependence of current on voltage
For a cell as assumed in Attwell & Laughlin (2001) (i.e. 200 Megohm membrane measured with a 10mV hyperpolarizing step, VNa=+50mV, VK=-100mV, Vrp=-70mV, [Na]o=[K]i=140mM, T=37C), assuming a Goldman voltage dependence for the Na<sup>+</sup> and K<sup>+</sup> fluxes through ion channels leads to PNa/PK=0.0746 and a Na<sup>+</sup> influx at the resting potential of 130pA, corresponding to an ATP consumption of 2.7x10<sup>8</sup> molecules/sec. This is 21% less than the 3.42x10<sup>8</sup> molecules/sec we calculated using an ohmic dependence of the currents on voltage. This difference is negligible given the variation of measured input resistances and the range of other assumptions that we needed to make. Furthermore, there are no data establishing whether the voltage-dependence of Na+ influx is better described by an ohmic or a Goldman equation.
(In a later post Dr Brette claims that the error arising is 40%. We suspect that his value arises from forgetting the contribution of the Na/K pump current to setting the resting potential, which leads erroneously to PNa/PK=0.05, and a 41.3% lower value than the ohmic dependence predicts.)
(1b) Cl<sup>-</sup> permeability
Our point was that the Cl<sup>-</sup> permeability was negligible. Which equation was used to derive that fact is therefore irrelevant.
(2) Pumps
We still disagree with the notion that, for a membrane with just Na<sup>+</sup> and K<sup>+</sup> fluxes, the system is unstable if it only has a Na/K pump. The Na pump rate is adjusted to match activity via its dependence on [Na<sup>+</sup> ]i and by the insertion of more pumps when needed.
(3) Cost of Na<sup>+</sup> extrusion at the mean potential
Tonic synaptic activity may depolarize cells by a mean value of ~4-8mV (Paré et al., 1998, J Neurophysiol 79, 1450). This will affect the calculation of “resting” Na+ influx negligibly (e.g. by ~6mV/120mV = 5% for a 6mV depolarization with Vrp=-70mV and VNa=+50mV). As stated in our earlier comment, this depolarization does not affect the ATP used per Na<sup>+</sup> pumped by the Na/K pump. Finally the ATP used on extruding synaptic ion entry is considered separately in the calculations.
(4) What input resistance tells us
For cortical L2/3 pyramidal cells the majority of the membrane area is in the basal dendrites, which have an electrotonic length of ~0.24 space constants, while the apical dendrites have an electrotonic length of ~0.69 space constants (mean data at body temperature from Trevelyan & Jack, 2002, J Physiol 539, 623). Larkman et al. (1992, J Comp Neurol 323, 137) similarly concluded that most of the dendrites of L2/3 and L5 pyramidal cells were within 0.5 space constants of the soma.
Elementary cable theory shows that, for a cable (dendrite or local axon) with a sealed end, with current injection at one end, the ratio of the apparent conductance to the real conductance, and thus the ratio of our calculated ATP usage (on Na<sup>+</sup> pumping to maintain the cable’s resting potential) to the real ATP usage, is given by (1/L).(exp(2L) - 1)/(exp(2L) + 1) where L is the electrotonic length (cable length/space constant). For L=0.24, 0.5 and 0.69, respectively, this predicts errors in the calculated ATP use of 1.9%, 7.6% and 13.3%, which are all completely negligible in the context of the other assumptions that we had to make.
For the axon collaterals near the soma, there is less information on electrotonic length, but the few measurements of axon space constant that exist (Alle & Geiger, 2006, Science 311, 1290; Shu et al., 2006, Nature 441, 761) suggest that the axon collaterals near the soma will similarly be electrically compact and thus that their conductance will be largely reflected in measurements of input resistance at the soma. We excluded the part of the axon in the white matter from our analysis, but did include the terminal axon segments in the grey matter (where the white matter axon rises back into a different cortical area. Re-reading after 16 years the source (Braitenberg & Schüz, 1991, Anatomy of the Cortex, Chapter 17) of the dimensions of these axons, it is clear that those authors were uncertain about the contribution of the terminal axon segments to the total axon length, but assumed that they contributed a similar length to that found near the soma in order to account for the total axon length they observed in cortex. It is unlikely that these distant axon segments will contribute much to the conductance of the cell measured at the soma but, partly compensating for this, part of the axon in the white matter will. This, along with the electrical compactness of the dendrites and proximal axons discussed above, implies that our calculated ATP use on the resting potential is likely to be correct to within a factor of 1/f = 1.57 (where f=0.64 is the fraction of the cell area that is electrically compact [ignoring the minor voltage non-uniformity quantified above], i.e. the soma, dendrites and proximal axons, calculated from the capacitances in Attwell & Laughlin and assuming that the proximal axons provide half of the total axon capacitance in the grey matter).
In fact the situation is likely to be better than this, because this estimate is based on membrane area, but ATP use is proportional to membrane conductance. Estimated values of the conductance of axons (Alle & Geiger, 2006, Science 311, 1290) suggest that the specific membrane conductance per unit area in axons is significantly lower than that in the soma and dendrites (see the Supplementary Information section on Granule Cells in Howarth et al. (2010) JCBFM 30, 403), which reduces the ATP used on maintaining the resting potential of axons.
General reflections on what people expect from the Attwell & Laughlin paper
Our paper tried to introduce a new way of thinking about the brain, based on energetics. Given the large number of assumptions involved it would be a mistake to expect individual values of ATP consumption to be highly accurate. Remarkably, the total energy use that we predicted for the grey matter turned out to be pretty well exactly what is measured experimentally. Nevertheless, constant updating of the assumptions and values is, of course, essential. It is interesting that the value we derived for the ATP used per cell on the action potential (3.84x10<sup>8</sup> ATP) was initially revised downwards nearly 4-fold in the light of papers showing less temporal overlap of the voltage-gated Na<sup>+</sup> and K<sup>+</sup> currents than occurs in squid axon (Alle et al., 2009, Science 325, 1405), but has increased with more recent estimates back to be close to our original estimate (3.77-8.00x10<sup>8</sup> ATP, Hallermann et al., 2012, Nature Neuroscience 15, 1007).
The most important assumption that we made was that all cells were identical, which immediately implies that this can only be an approximate analysis. We were very happy that the total energy use that we predicted from measured ionic currents, cell anatomy and cell densities was so close to the correct value.
General reflections on post-publication peer comments
We believe that if someone has questions about a paper then the most productive way to get them answered is: (i) to think about the issues; if that fails (ii) to write to the authors and ask them about the questions, rather than posting some vague and erroneous comments that will forever be linked to the paper, regardless of their validity; and if that fails (iii) to write a paper or review which goes through peer review, pointing out the problems. Peer review is crucial for determining whether the points are valid or not - it potentially saves many readers the time needed to read possibly erroneous comments.
It takes a long time to reply to such comments, and we feel that Dr Brette could have done the calculations that we have provided in our two sets of responses. We will not be posting further responses therefore.
David Attwell & Simon Laughlin, 09-02-17
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- Jun 2018
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develop and validate measures of writing quality
I think you can see this growth in writing over time. By having students engage in multiple pieces of authentic writing we may be able to parse growth.
Think about annotations and developing a code book to annotate over time. That is clearly demonstrable growth thaty could easily be analyzed.
Tools that make teachers more reliable are just as important.
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www.bibleodyssey.org www.bibleodyssey.org
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After reading “Gilgamesh and the Bible” I am not surprised that “The Epic of Gilgamesh” and the Hebrew Bible have similar stories. To be honest, the bible has been translated so many times I am not surprised that the original may have been copied and somewhat changed. After all, there is so much good information it may have been plagiarized by others who wrote the bible. Unfortunately, a lot of people take something and translate it their own way or to simply have a better understanding of how man kind started. The article explains that start, the problems, and the consequences, and death of human life. Even back then temptations will come along, the humans will fall into a trap, and have to deal with the consequences of their actions. Today people still have to face the same problems that they did back then like being tempted to drink beer, separate themselves from nature, dating the wrong people, and look up the god like figures. I believe that people should unite without having to depend on religion or opinions of others, we as humans can be strong individuals. We have to believe in ourselves, not go against nature, heal our inner souls; we will have stress free easier lives to live by. What stood out to me the most in this article was the poem at the end. It simply says that our life will end eventually so we must enjoy it while we can. Eat well, bathe, take care of our children, and let the woman be free. I think this sure is the way of life and we can get over every hurdle that life throws at us.
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forboredom.realtimecollective.com forboredom.realtimecollective.com
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Why does boredom seem painful? Shouldn’t it just be boring?
While self-shattering is nonviolent, there are many other ways that thanatos, the destructive instinct, is twinned with boredom
Renata Salecl acknowledges the twinning of boredom and aggression when she writes that the society “which allegedly gives priority to the individual’s freedoms over submission to group causes” (2006) and filters choice through the prism of “opportunity cost” is one that “causes aggression towards [the self] and apathy in relation to contemporary social problems which are completely ignored by the emporium of individualist choices” (2013a).
Sometimes the aggression turns outward, as well. The Internet troll as bored, isolated malcontent is well established as a cultural trope and borne out by empirical data (Sanghani 2013). Liam Mitchell (2013) even ups the ante on this notion by proposing that the troll tackles the “desire for desires” problem by erecting “a conscious barrier to unconscious desire” by eliding investment in its principal object, which is amusement at another’s expense, or “lulz.” In Mattathias Schwartz’s (2013) formulation, lulz is “a quasi-thermodynamic exchange between the sensitive and the cruel”; humour derived from “disrupting another’s emotional equilibrium.” In pursuing lulz, the troll establishes “a distance from other trolls (with whom he may or may not feel a bond) and from the people who are governed by normal formations of desire” (Mitchell 2013). Insofar as the troll’s pursuits “bypass or forestall normal formations of desire, they may be characterized as non-subjective.” This is significant because, as Mitchell says, our choices only “have lasting meaning, for others and for ourselves … when we can be held accountable to our promises,” and this is impossible in a condition of both online anonymity and refusal of subjectivity.
The study “Just think: The challenges of the disengaged mind” (Wilson et al. 2014) asked participants to spend some time alone thinking in an empty room. There were three study conditions, in all of which participants generally gave high ratings of boredom. In one condition the experimenters gave people the option of giving themselves a mild electric shock. 67% of men and 25% of women shocked themselves. So goes the saying “the devil makes work for idle hands.”
Or more broadly: there are many ways, as Baudelaire said in Les Fleurs du Mal (1857, xxv), that “ennui makes your soul cruel.”
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via3.hypothes.is via3.hypothes.is
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There may be frustration that more progress wasnot made, or that some misunderstanding still remains,but we can’t expect everything in real life to be totallysuccessful. The consultation will have been a failureif, at its end, the client feels that the consultant wasnot listening, or was not interested in trying to under-stand the problem, or did not know enough Statistics tosolve the problem.
I think this is a great thing to focus on and keep as a reminder for any kind of consulting project. If we can maintain a solid relationship with the client, solutions do happen.
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www.ethanzuckerman.com www.ethanzuckerman.com
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including the argument to burn it all down
It would be truly amazing to see how the world would be without the internet now that we are surrounded and completely submerged in it as a society. Some may say well we did it all the time before the late 80's so it shouldn't be that hard. That is true however back then the internet wasn't even fully evolved like it is today and/ or used by the majority yet. I think it would definitely be a different story today because we are reliant on it for everyday purposes. I mean hey I'm taking an entire course online as we speak!
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thewirecutter.com thewirecutter.com
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After more than 40 hours of research and over a month of testing 13 devices, we think the GreatCall Lively Mobile is the best medical alert system for most people. Unlike most devices, it can reach either 911 or a call center from anywhere in your home or out in the world. That means the GreatCall Lively Mobile can help in all manner of situations, from getting EMTs and loved ones on the scene after a fall to contacting a friend for you if you can’t find your phone (yes, really; we tried it). Share this review on Facebook Share this review on Twitter Save this review on Pocket Share this review on Pinterest Share this review with E-mail It’s less expensive per month than any similar device, and relatively stylish, too. But choosing a medical alert is a personal decision, so there are different factors to consider: If you won’t wear a medical alert that looks vaguely like a medical device, won’t remember to charge a medical alert, or will have trouble pushing a button during an emergency, we have picks for you, too. Our pick GreatCall Lively Mobile The best medical alert system Our favorite medical alert system is comfortable to wear around your neck or on a belt clip. We found that the call center picks up faster than the competition, typically 15 seconds after you push the button. $40 from GreatCall $34 from Walmart The water-resistant GreatCall Lively Mobile can dial a call center or 911 directly (the ability to do both is a rare feature) from anywhere, and it’s easier to wear than the competition: It can go on a lanyard (with a magnetic clasp) that’s long enough to slide over your head, or on a belt clip. The silver box and plain white indicator light are more understated than the competition, and GreatCall offers the lowest-cost month-to-month plan of anything we looked at. The battery lasts 24 hours, according to GreatCall, though we found it could go up to 50 hours with minimal use. The advertised battery life is on the low end of the models we tested, but our experts recommended getting in the habit of charging your medical alert every day anyway. The GreatCall Lively Mobile works anywhere there’s Verizon cell service, which we’ve found to be the most reliable network. Advertisement googletag.cmd.push(function() { googletag.display('div-gpt-ad-1524661673579-0'); }); Also great Lifestation At Home An at-home medical alert system Call for help from a room or two in your house with this less-expensive and easier-to-wear system, available in versions that connect to a landline or cell service. $26 from LifeStation If you are with someone whenever you leave your house and have a small living space, or just want protection in one place (like the shower), you might not need a mobile medical alert like our pick. An at-home medical alert is less expensive with a less bulky button to carry, but the range is very limited. Most at-home systems are similar, but we found the Lifestation At Home to be a little easier to use and less expensive than the competition (month-to-month plans are $30 per month for a device that connects to a landline, and $37 per month for one with cellular service). The major downside of the Lifestation At Home is that you cannot speak directly into the device. If you fall, you can push the button from a few hundred feet away from the base station to dial the call center, but you’ll need to be within shouting distance of the base station to communicate whether you’re in need of 911 help or just want an emergency contact to come help you get up. (If you are unable to speak, or the call center cannot hear you, they will follow a course of action that you specify when you sign up: call a family member, call EMTs, or some combination thereof.) The battery in the wearable button lasts three years, and the base unit plugs into the wall. The button connects to the base via radio signal. Also great Apple Watch Series 3 (aluminum) No call center and no contract Bare-bones emergency features, but the most stylish. $330 from Apple If looks matter to you and you have an iPhone, or if you may have trouble pushing a button in an emergency, consider the Apple Watch Series 3. Though it’s bare-bones in emergency functions, it’s much more discreet to wear than other devices we tested. Because compliance matters more than anything when it comes to these devices, wearability is important. At a one-time cost of a few hundred dollars, the Apple Watch works out to be less expensive than buying a separate medical alert with a monthly bill after about a year of use (not including the cost of iPhone service, which is required for the Apple Watch to place phone calls). A button on the side of the watch allows you to place a call to 911 and can alert your emergency contacts that you placed a call when you are in range of your phone or connected to the same Wi-Fi network, and you can speak directly into the watch. You can also place an ordinary nonemergency call through the watch, either by scrolling through your contacts list or saying, “Hey, Siri, call [contact].” The Apple Watch battery lasts 18 hours with some use (less if you’re using it to make frequent phone calls). In September 2017, Apple announced a version of the watch with LTE, but we recommend the one without cellular connectivity for now. Budget pick Ask My Buddy A bare-bones option for home A voice-controlled app that can give you added peace of mind, but can’t call 911. Buy from Ask My Buddy Amazon Echo Our favorite voice-controlled device It’s relatively easy to set up Ask My Buddy on the Amazon Echo, which can also play music, tell you the weather, and control smart devices. $180 from Amazon Buy from Amazon Buy from Amazon Buy from Amazon If you want an extra layer of security at home and are considering getting a voice-controlled smart-home device anyway, Ask My Buddy is a free service available on the Amazon Echo (here’s our full guide on Amazon’s Alexa devices). If you need help and are in the same room, you can say “Alexa, ask my buddy to send help” and your emergency contacts will get a notification via email, text, or robocall. You can also place a call through the Echo to anyone with an Alexa device, or the app. Of all the medical-alert-capable devices, the Echo plus Ask My Buddy is one of the least expensive and least intrusive options. However, it offers very minimal protection: It can’t travel with you, and it can’t actually call 911 or reach anyone who is constantly available to dial 911 for you if you ask. We wouldn’t rely on any medical alert alone to save us in an emergency where every second counts, anyway, but this one ranks the lowest in terms of how much it can help in a variety of situations. Keep up with everything Wirecutter from your inbox Wirecutter Weekly: New reviews and picks, sent weekly Deals We Love: The best deals we can find, sent daily Please choose a newsletter to subscribe to. Sign up for Wirecutter's Newsletter Subscribe That wasn't a valid email address. Please try again. Feel free to opt out or contact us at any time. Opt out or contact us at any time. Thanks for subscribing! You'll be hearing from us soon. The research Expand all Why you should trust us Who should get this Can I just use a cell phone, a smart watch, or Alexa/Google Voice? How we picked How we tested What medical alerts are like to use and wear Our pick: GreatCall Lively Mobile Flaws but not dealbreakers Also great: Lifestation At Home Also great: Apple Watch Also great: Amazon Echo with Ask My Buddy What to ask in a test call Why we don’t recommend Life Alert The competition Sources Why you should trust us Medical alert systems (sometimes referred to as personal emergency response systems) have been around for decades. Perhaps the most recognizable name brand, Life Alert, with its ear-worm of a slogan “I’ve fallen and I can’t get up,” was founded in the 1980s. To understand how people use medical alerts, I spoke to George Demiris, PhD, a professor in the department of biomedical informatics and medical education at the University of Washington; Marita Kloseck, PhD, director of the Sam Katz Community Health and Aging Research Unit at Western University in Ontario, Canada; and Majd Alwan, senior vice president of technology and executive director of the LeadingAge Center for Aging Services Technologies. I also spoke to experts who help people select medical alerts: Mindy Renfro, who has worked as a physical therapist and is currently a research assistant professor at the Rural Institute On Disabilities, part of the University of Montana; Richard Caro, who writes about medical alerts at Tech-enhanced Life; Tony Rovere, chair of the Long Island chapter of the National Aging in Place Council and blogger at StuffSeniorsNeed.com; and Melissa Kantor, the executive director of Long Island at Home, which sells medical alerts and aging-in-place services to local seniors. I fall well below the typical age at which people purchase a medical alert, so I approached the research as though I were selecting one for a loved one to use. According to experts, I’m not far off from a typical customer: Many medical alerts are purchased by adult children looking for ways to better support a parent who is aging in place. I spent weeks trying out the devices for myself. I also consulted a family member who already uses one, my great-aunt Kay. Who should get this Pull QuoteOut of the 30 medical alert users in Ontario, Canada, that Kloseck and her colleagues spoke to, 90 percent agreed that the devices helped them maintain their independence. My great-aunt Kay lives alone in Erie, Pennsylvania, near the farm where she and my grandma grew up. She’s had a couple nasty falls in the past five years, but she doesn’t want to live in a nursing home. She prefers her own house and her daily routines. But she wants to know that if she needs to, she’ll be able to call for help quickly. Her medical alert device helps her maintain an independent lifestyle, as it does for many. “I dread just being an ill person who can’t cope with daily looking after yourself,” said one participant in the focus groups researcher Marita Kloseck conducted on what it’s like to live with a medical alert. “The last thing I want to do is lose my independence and be an invalid, it’s my biggest fear.” If you’re living independently and at risk for falling or another medical emergency, a medical alert is one safety measure to consider. Out of the 30 medical alert users in Ontario, Canada, that Kloseck and her colleagues spoke to, 90 percent agreed that the devices helped them maintain their independence. Though many people, like Aunt Kay, turn to medical alert systems after they’ve had a scary incident, the best time to get one is before you need it. If you are having trouble standing up to get out of a chair, said Renfro, it’s a good time to consider one—especially if you live somewhere where neighbors are few and far between, as is the case in Montana, where Renfro works. It’s not just for falls. One interviewee in Kloseck’s focus group reported successfully contacting EMTs via a medical alert after indigestion-like pain for over a day. “I think they must have flew here!” Another said she liked having a medical alert in case someone suspicious showed up at the door. A medical alert might simply relieve anxiety about emergencies. “You hear about people who fall and then can’t get help and they lay there for sometimes hours, but it just scares you when you think that could happen,” noted one participant in Kloseck’s survey on what motivated her to get a medical alert. “Subscribers reported feeling a sense of security or peace of mind,” Kloseck writes. As Aunt Kay puts it: “I feel protected.” Pull QuoteYou should get a medical alert only if you’re committed to wearing and using it. A medical alert should be just one line of defense against any medical emergency, along with working with a physician or physical therapist to monitor or improve your health and eliminating any hazards around the house, said Alwan. No devices we tested worked perfectly, and no medical alert will undo the damage of a fall (or anything else). Though all experts I spoke to agreed that medical alert systems made you safer, it’s hard to tell by how much. Studies suggest that these systems can reduce the amount of time spent on the floor after a fall, but there’s nothing conclusive in the way of peer-reviewed work showing how many lives they save per year. (In fact, experts I spoke to mostly said that their own parents didn’t have medical alerts, preferring to rely instead on check-ins with a friend or neighbor). You should get a medical alert only if you’re committed to wearing and using it. “I don’t even move without it,” Aunt Kay said. It doesn’t do any good sitting atop your dresser, or if you don’t feel comfortable pushing the button in an emergency. They make poor surprise gifts, says Renfro. If you’d like to foot the bill for a device for a loved one, make sure it’s something they want, and involve them in the process of picking it out. Can I just use a cell phone, a smart watch, or Alexa/Google Voice? Today, many of us already carry around a emergency help button: our cell phones. In fact, for some, the ability to dial 911 is the main appeal of having a wireless device at all, according to the Federal Communications Commission. If you’re in the habit of carrying around a phone constantly, it might be a good alternative to a medical alert. There are a few downsides: Most important, your phone might not be water-resistant, or at least might be awkward to take in the shower and hard to reach if you slip. It doesn’t have an option for automatic fall detection, which some medical alerts do. In a nonemergency it can’t reach a call center, so you’ll have to dial family until someone picks up. And it’s not set up by default to automatically share your location, as many medical alerts will with the call center agent. A phone’s battery also doesn’t last as long as a medical alert system’s, if you’re using it to do other things. However, if you know you’ll have trouble remembering to wear a medical alert, or can’t afford $20+ per month, committing to keeping your phone on you at all times is better than nothing. Some companies have apps that provide access to a call center just like medical alerts do, at about a third of the price of a monthly medical alert subscription. However, some can be confusing to use, slow to load, and even sometimes freeze, according to Caro, who tested out three of the apps. They’re also stuck behind a lock screen. There are a few devices that offer medical-alert-like features that are not technically medical alerts, including the Apple Watch and other smart watches, Amazon Alexa devices, and Google Home. Though these devices can offer emergency features, none will be as reliable as a device that has the sole purpose of reaching help. If you know you won’t wear a traditional medical alert, these are better than nothing. How we picked There’s a medical alert for every lifestyle. The most important feature of a medical alert system is that it’s something you are willing to use. Not even the most reliable device will be of use if it’s stashed in a drawer. Comfort and stylishness tended to decrease with range, I found. (A notable exception to this was the Apple Watch, which was the most comfortable and stylish of the bunch, and can go anywhere as long as your iPhone goes too.) We ended up testing a wide range of devices that covered all the possible configurations, but here’s how to figure out which kind works best for you. (Finding a device that you like might involve some trial and error: it took Aunt Kay two tries to find a medical alert that works well for her needs, and some time after that to figure out how to wear the device in a way that’s comfortable.) If you have a living space that’s bigger than a couple rooms, or if you leave your house alone, a mobile medical alert, which can go anywhere there’s a cell signal, will work best to keep you safe. They consist of a unit a little smaller than a deck of cards that you wear around your neck or on a belt clip that houses a GPS system, a speaker, and a microphone. The button calls someone directly from the device, and you speak to them through the unit. The button on most mobile medical alerts dials a call center (though our favorite can also reach 911). Agents are available 24/7, and pick up anywhere between 15 seconds and two minutes after you press the button. They can send 911 to your house, call a friend or family member on your behalf, or simply keep you company while you troubleshoot the situation yourself. They typically have a $20 to $70 monthly fee that includes the cost of the service and the device. (There’s often an activation or equipment fee, too.) Mobile medical alerts work off mobile carriers (e.g., AT&T, Verizon), so you’ll need to check the coverage in your area before making a purchase. They also need to be charged daily, or every few days, depending on the model. If you don’t want to call 911 directly in a minor emergency or if you slip in the shower while you’re naked, mobile medical alerts offer a way to get a variety of help, via a call center. The call center employees are there 24/7, unlike family members who will inevitably be sleeping, in work meetings, or on vacation sometimes. Further, mobile systems that connect to a call center almost always come with an option for automatic fall detection for about $10 extra per month (if you don’t like it, you can turn it off). When the device senses a change in vertical acceleration, it calls for help. If you are totally knocked out, the operator will attempt to figure out your location via the GPS signal from the device. Fall detection is a great idea, in theory, said experts. In practice, it’s prone to registering false positives, or failing to detect actual falls. “It can be embarrassing, it can [disrupt] activities, it can be costly,” said Demiris. (Part of the problem: Stunt actors falling accidentally on purpose are often used to calibrate fall detection.) Even if the device does successfully make a call after you’ve slipped, if you’ve been knocked unconscious, the operator at the call center could still have trouble figuring out where to send help. Most mobile systems have built-in GPS, but the little dot that shows operators where you are is subject to drift around. (Have you ever opened Google Maps on your phone and had the blue dot appear somewhere you aren’t? That’s it.) There are technical improvements that can be made on bare-bones GPS—like a device that checks in with Wi-Fi signals, when possible—but no device will always pinpoint your location accurately. At-home medical alerts are devices that are for use just at home, with a base station that can be connected to cell service or a landline. With just a few exceptions, these consist of a small, light button that can be worn on your wrist or around your neck. Push the button within about 600 feet of the base station (they’re connected via a radio signal), and you can speak to an operator through the base, which looks kind of like an answering machine. These medical alert systems tend to have lower monthly costs, and a device that’s far less bulky and annoying to wear (it’s about the weight and diameter of a quarter). There’s nothing to remember to charge, either. But the limited range can be frustrating, according to participants in a survey conducted by researchers at Jönköping University in Sweden, not just because it limits movement. “In particular, they felt that the lack of new technical innovations in the alarm system, such as the inclusion of a global positioning system (GPS), was a clear indication that their needs were not considered priorities in society,” the researchers write. A homebound system can make you feel homebound, which isn’t useful for people who want to be active outside of the house. Some companies offer affordable devices that can be used to call a loved one or even 911 directly. They do not reach call centers or have their own cell service (the two features are typically paired). These are less expensive because they lack a monthly service fee; rather, they rely on Wi-Fi, a smartphone, or a landline. They range from specialized medical alerts to the Apple Watch. No matter what style of medical alert you want—mobile or traditional, with a call center or not—you have a few options for how you’ll wear the device. Medical alerts can hang around your neck or wrist, or clip to your belt; for any particular device, there are often at least two options. What works best is largely personal preference, though Demiris notes that a device worn around your neck can be easier to make a habit of wearing if you’re used to putting on jewelry in the morning (it’s also necessary if you are using automatic fall detection). Battery life varies broadly for medical alerts, anywhere from just a day to a week. Experts advised getting in the habit of charging the device every night, so we didn’t prioritize long battery life. There’s typically no volume control on medical alert systems, which are about as loud as a cell phone at top volume and on speaker. The advantage is that there’s no way to accidentally turn the volume down. However, if you’re hard of hearing, volume could potentially be an issue. We looked only at devices that came with the option to make monthly payments or required no payments at all, and we discarded any that require you to have an annual contract for the service on the advice of Tony Revere, who blogs at StuffSeniorsNeed.com. You should be able to send the device back without breaking a contract if you try a particular one and realize it—or the whole concept—just isn’t for you. There are various certifications that medical alert equipment and call center equipment can have to make sure they’re up to certain safety standards. For example, companies can pay Underwriter Laboratories to verify their device has certain features. Experts we spoke to disagreed on the level of importance of these certifications, but no one thought that it was a dealbreaker to not have one. And because we did our own testing, we were able to learn firsthand if a system was reliable. Some companies will advertise that their call center is based in the US. Caro, who writes about how to pick a medical alert on Tech-enhanced Life and logged many hours himself testing medical alerts, pointed out to me that all the call centers he’s encountered sounded like they were based in the States. How we tested It’s hard to tell a lot about how easy, effective, and comfortable a medical alert is from descriptions online or from people who may have only used one on their own with no point of comparison, so we decided to try the devices ourselves. I spent several weeks integrating the devices into my life, and then pushing their limits as much as possible. I went through the setup process for each device, which ranged from placing the device in a charging cradle (which all mobile medical alerts use) and following a few verbal instructions, to leafing through a fine-print manual. One device required a traditional landline; I trekked to a coworker’s parents’ apartment on the Upper West Side to use one after it wasn’t compatible with our VoIP system at work. I used each medical alert for at least a day, wearing the mobile medical alerts to work and out with friends, making test calls in all manner of locations. For a while in February, my outfit was consistently punctuated by a low-hanging, blinking device, my kitchen counter and bedside table littered with in-home devices and charging cradles. I made several test calls with each device and compared both response time and the quality of customer service. We prioritized devices that could be worn a variety of ways and made accommodations for people without fine motor skills, like a lanyard with a magnetic clasp that doesn’t need to be looped over a head. Some devices require dexterity not everyone has, like pushing a lanyard through a small hole, or attaching them to a belt clip. What medical alerts are like to use and wear When I wore the Medical Guardian Premium Guardian, a former runner-up pick, out one night with my coworkers, the diamond indicator light blinked red as I ate my food. In the course of chatting about work, I mentioned that I was trying out medical alerts. “Oh that’s what that thing is,” one coworker said. “I thought maybe you had an allergy.” While I was getting used to having a medical alert on me, they still read as a medical device and a little bit strange to the outside world. I was surprised and delighted to learn during this process that, despite the fact that advertising for these devices seems to prey on our fear of mortality and disaster, I didn’t have to be in a life-or-death situation in order to buzz the call centers. The operators are just as happy to help talk through a situation and provide support from afar, and never seemed to be itching to push me into declaring an emergency. The buttons for in-home medical alerts are all tiny and barely noticeable. Mobile medical alerts were the biggest nuisance to wear, in part because of their size, and in part because they tag along for all manner of social situations. They are heavier and can draw considerable attention. I got in the habit of tucking the medical alerts into my shirt, per Aunt Kay’s advice. Some made their presence known even when they were out of sight, chiming to indicate their charge status when I was in a crowded elevator at work, or even speaking up at inopportune times. One day at work, the Premium Guardian verbally announced to me and everyone in a two-cubicle range that its battery was low. I spent a lot of time doing the dreaded thing—pushing the button to ask for help—just to see what would happen. Some devices made chiming sounds, some vibrated, and some noted that they were dialing the call center. The best medical alerts continuously did something as I waited for someone to pick up, as long spaces of silence would leave me wondering if I had accidentally hung up or lost signal. For medical alerts with call centers, someone typically picked up within 30 seconds. Longer than that felt like an eternity, even from the safety of my desk or bed; I wouldn’t want a loved one waiting that long during an emergency. All call centers say more or less the same line when they pick up: “Hello, do you need help?” I usually said no, I was just placing a test call. In one instance, curious if the call center would be willing to help out in a truly minor situation, I asked the operator to call my boyfriend to tell him I was running late to meet him. The operator was happy to oblige. Voice-controlled units like the Amazon Echo don’t require you to wear anything, but work reliably only when you’re in the same room. I set up the Echo in my kitchen, and when the dishwasher was running, even when I was screaming “Hey, Alexa!”—the signal that you’re about to give the device a command—over and over from a room away, it could not hear me. (This is also a pitfall of relying on a device to play music and be able to hear you in an emergency.) I had similar experiences with traditional in-home medical alerts. The range on these devices is technically several hundred feet from the base station, and though the call center operators could hear me yelling from a room away, they had trouble understanding me. (I just moved closer to the base station, but in the event that you fall and they can’t hear you, they’ll follow a preplanned course of action that you decide when you sign up, like calling a family member and then EMTs.) Services that try to use both the button and a base station to communicate were suboptimal. In the case of one hybrid mobile and home device, an operator first tries to talk to you via a stationary home box, and then switches to the wearable if you don’t respond there. After pushing the button at work, I sat in an empty conference room for a full two minutes while, presumably, someone first tried asking my empty apartment if anyone needed help before switching over to the speaker around my neck. During test calls, I asked operators to identify my location. No GPS was consistently accurate, though they were often correct within a couple blocks. This makes backup measures attractive, like the GreatCall Lively Mobile’s Web interface where you can log your typical schedule. Sometimes the GPS was way off. Once, while testing the Bay Alarm Medical GPS Alert System, an operator said that I was at the New York Times building in midtown where the device had lost power, when in fact I’d gone home to Brooklyn. The device lost power downtown, and had only just been recharged when I placed the test call; I suspect that it hadn’t been on long enough to update its location. On another occasion, the GPS on a device wasn’t working at all, and took two phone calls to customer service to fix. I found that operators were rarely able to troubleshoot problems with the device or answer questions about service. Though call center employees were willing and able to help with even minor incidents, they weren’t inclined to make small talk. Once, after noting my location an operator did exclaim that she used to live on my street, and we had a short conversation about the rising rents in Brooklyn. But with few exceptions, the call center people hung up quickly after addressing my requests. Despite being vaguely worried when I started this project about accidentally having EMTs show up at my house, I never once pushed the button on a medical alert unintentionally during testing, including a few occasions when I just threw them in my purse. If you do accidentally hit the button, chances are you will be connected to a call center, and you can just clarify what happened with an operator. (Medical alerts make noise when they are placing a call, so a butt-dial will not go unnoticed.) Most medical alerts do not call 911 directly, and those that do require a more deliberate, prolonged push to reach emergency services. At first I skipped providing my emergency contacts, in part because I didn’t expect to be in immediate danger, but also because it was such an easy step to overlook. In all but one case, it was possible to get through the activation process without providing them, which you typically have to do over email, fax, or via snail mail to ensure that the contact information is entered correctly. Only one model, the GreatCall Lively Mobile, allowed you to enter them in an online interface. Our pick: GreatCall Lively Mobile The GreatCall Lively Mobile is intuitive to use, and has a plain design that won’t draw too much attention. Our pick GreatCall Lively Mobile The best medical alert system Our favorite medical alert system is comfortable to wear around your neck or on a belt clip. We found that the call center picks up faster than the competition, typically 15 seconds after you push the button. $40 from GreatCall $34 from Walmart The GreatCall Lively Mobile was one of the easiest mobile medical alerts to wear and use, and costs less than any other medical alert of its kind that we considered, with service starting at $20 per month, with one-time fees totaling $80. The rectangular silver and black (or gold and black) design draws minimal attention, and the call center consistently picks up quickly—up to eight times as fast as others. The battery life is 24 hours, according to the company, among the the shortest we considered, though I found it lasted nearly twice that long with minimal use. The device is a little smaller and lighter than a deck of cards. One big button in the middle dials the call center or—if you hold it down—911. A small button on the back turns it on and off. A small battery-indicator light changes colors when the Lively is low on charge, but it doesn’t draw a ton of attention to itself. When the Lively shuts off from low battery, it announces that it’s doing so. (It was loud enough to wake me up at 4 a.m. one day, a good feature if you’ve forgotten to charge it and have missed the battery light.) The Lively Mobile can go anywhere there’s Verizon cell service, including your shower, as it’s waterproof. In separate tests, we’ve found Verizon to be the most reliable network, though it doesn’t cover every part of the country. Check here to see if your area is covered. The Lively Mobile is one of the only medical alerts we looked at that has the option to call either a call center, or—by holding down the button—911 directly. The speaker and microphone in the device provide sound quality that’s better than that of many other devices we considered. If you dial an agent from the Lively, they’ll typically pick up about 15 seconds after you push the button; other devices left us hanging for what felt like forever. If you are lost, or unable to speak, the agent can look at a GPS signal and a list of places you frequent to help identify your location. The Lively Mobile is the only device that has an easy-to-use online interface where you can store emergency contact information. With all other devices, you have to email or snail mail your emergency contact information (this ensures accuracy compared with speaking the information over the phone). GreatCall offers the most affordable basic service packages of all the mobile medical alerts we tested, at $20. Fall detection costs an extra $15. GreatCall also has a middle tier, for $25, with access to doctors via the device (though they emphasize that this feature should not be used in an emergency), and allows family and friends to tell when you leave home or return via the GreatCall Link app. The first tier of service should work well for most people, though if the idea of being able to loosely track a loved one’s movements appeals to you, or if you want the extra security of (somewhat unreliable) fall detection, consider upgrading. The Lively Mobile has a separate on-off button, which means it’s impossible to accidentally turn it off when you’re calling for help. The lanyard is soft and black, shorter than those of much of the competition, and has a magnetic clasp so you don’t need to be able to lift your arms above your head to put it on or mess with a complicated closure. (There’s also an option to wear the device on a belt clip). The instruction booklet for the Lively Mobile is easy to read. This is a small point, but it was much better than the thick, tiny-print instruction books that some of the competition had. GreatCall has been around since 2006—the company is best known for making Jitterbug flip phones—and debuted the Lively Mobile in mid-2016. The device is an upgraded version of GreatCall’s previous mobile medical alert, the Splash, which garnered positive reviews. Medical alert reviewer Caro praised the Splash for the call center’s fast response time, ability to call 911 directly, and easy online interface, all qualities that the Lively shares. Flaws but not dealbreakers No medical alert is actively enjoyable to wear, and the Lively Mobile is no exception. It will likely take some time to get used to having the device around your neck. On the Lively, a white light flashes consistently to indicate that it’s in an area with service. Though this was less intrusive than the more colorful lights on some other devices, it could still be annoying; there were no mobile medical alerts without lights. The length of the Lively Mobile’s lanyard is not adjustable. Though I found the relatively short lanyard to be easier to wear than the competition’s, this might not be the case for everyone. Even though the lanyard can be easily swapped out, most traditional lanyards (which have a clasp that attaches to a badge) will be a little awkward. If you want a different lanyard with a specific length, you’ll need a little DIY savvy. If your area is not covered by Verizon, the Lively Mobile won’t work for you. Check your coverage here. Another flaw that all medical alerts share: the GPS signal can be unreliable. However, the Lively helps skirt this by prompting you to enter information into an online database (from a computer or a smartphone app) about your schedule and where you go during your days so the call center staff have something to fall back on. It’s the only medical alert that has this feature. Of all the medical alerts we tested, the Lively Mobile has one of the shortest advertised battery lives: 24 hours, as opposed to 36 hours or even several days. I found the battery lasted over 50 hours with minimal use, though I wouldn’t want a loved one counting on it working for that long on a single charge. Experts recommend getting in the habit of charging your medical alert nightly, so that you don’t have to think about it. If this will be hard for you, consider an in-home medical alert, which doesn’t need to be charged. Also great: Lifestation At Home The LifeStation At Home system has a small button and a base station. Also great Lifestation At Home An at-home medical alert system Call for help from a room or two in your house with this less-expensive and easier-to-wear system, available in versions that connect to a landline or cell service. $26 from LifeStation If you just need a medical alert to cover you in a couple rooms of your house, consider the Life Station At Home system, which is about $30 per month (there’s no activation fee). Like all in-home medical alert systems, it consists of a small button that you can wear around your neck or on your wrist that wirelessly connects to an answering-machine-like base station that lets you speak to a call center agent (there’s no option to dial 911 directly). Though it can’t leave your house, and you can’t speak through the button, it’s easier to wear than our top picks. There’s no charging required; the button’s battery lasts about three years. Home medical alert systems are all very similar, but Life Station’s is a little less expensive than other options we looked at, and didn’t give us any trouble during testing. The main perk of an at-home system is that the device is much easier to wear than those in mobile systems: The Life Station button is about the weight and diameter of a quarter, and just a little thicker. In comparison, our main pick and runner-up are just a little smaller and lighter than a deck of cards. If you don’t need a medical alert that you can leave the house with, are mostly concerned about slipping in one room—the bathroom, for example—or know that you just won’t wear anything but the least-intrusive device, the Life Station At Home might be a good option. The major downside of this or any at-home system is that its range is incredibly limited, even if you’re just using it in your home. The range of this device is several hundred feet—that is, the button can still communicate with the base station if you are on the other side of a small house. Though it’s difficult to communicate through the base station if you’re even one room away, you can choose at the time of setup what course of action the call center should take if you push the button and they don’t hear anything. Also great: Apple Watch A medical ID screen has a few details for paramedics. Apple Watch can dial 911 at the push of a button. The Emergency SOS feature dials 911 and texts your emergency contacts. Press the button on the right once to get this screen, or hold down to activate the SOS feature immediately. A medical ID screen has a few details for paramedics. Apple Watch can dial 911 at the push of a button. 1 of 3 Also great Apple Watch Series 3 (aluminum) No call center and no contract Bare-bones emergency features, but the most stylish. $330 from Apple Apple Watch Series 3 has basic emergency functions compared with most medical alerts we looked at, and requires a little tech savvy to use. Out of everything we tested, it’s the only wearable device that’s stylish and doesn’t look at all like a medical device. (We tested the Series 2 but it is no longer available). You will need to have an iPhone for the watch to work, but if you’re already paying for that service and you are comfortable with navigating Apple services, the watch may be relatively affordable—it currently costs $330, which will buy you less than 10 months of service with a typical mobile medical alert. (We recommend the version without cellular service; more on that in a minute.) The SOS feature (which was introduced on the Series 2 model) allows users to dial 911 by pushing and holding down the button on the side of the watch, and can automatically text up to three emergency contacts and give them your location when you do so. Apple Watch hasn’t had emergency features long enough for our experts to evaluate its usefulness as a medical alert, though they agreed it could be useful. Apple Watch’s battery lasts 18 hours with some use. You can speak to a 911 responder directly through the watch, or if it’s a nonemergency, you can dial a friend or family member through the watch verbally, by saying (for example), “Siri, call [name].” The sound quality of Apple Watch is better than any medical alert we considered. There are a variety of bands to choose from (some costing hundreds of dollars themselves, like a Hermes band), making Apple Watch Series 2 the most customizable of all the devices we looked at. Aside from the limited functionality, the major downside of Apple Watch is that you have to be within Bluetooth range or connected to the same Wi-Fi network as your phone for it to place a call. This means that you can’t necessarily just set your phone down in your house, wander away from it, and know that your Apple Watch is going to keep you safe in the event of an emergency (one of the key advantages of a true mobile medical alert system). There is an LTE version of the Series 3 that allows you to place calls without being in range of your phone, but we can’t recommend it. Preliminary reviews have noted connectivity and battery issues with the LTE version, plus you’ll need to pay about $10 a month for the Watch to have its own service. We plan to test the service for ourselves, and we’ll keep an eye out for improvements. I found that navigating the tiny screen on the watch could be challenging, though this was mostly an issue for using functions other than the SOS feature. (However, if you buy Apple Watch, you’ll likely want it to work for other things, too.) If you find yourself fairly comfortable with most Apple devices, and okay with the size of newspaper print (the font can be enlarged on some apps, like text messaging, but not all), scrolling through apps on your wrist shouldn’t be too much of an adjustment. Also great: Amazon Echo with Ask My Buddy At your verbal request, the Amazon Echo can send an alert to loved ones. Budget pick Ask My Buddy A bare-bones option for home A voice-controlled app that can give you added peace of mind, but can’t call 911. Buy from Ask My Buddy Amazon Echo Our favorite voice-controlled device It’s relatively easy to set up Ask My Buddy on the Amazon Echo, which can also play music, tell you the weather, and control smart devices. $180 from Amazon Buy from Amazon Buy from Amazon Buy from Amazon If you don’t carry your phone around in your home, won’t remember or want to wear even a small button, would have trouble using a button in an emergency but can vocalize and enunciate pretty clearly, or just want another layer of security, consider using Ask My Buddy paired with the Amazon Echo (you’ll need to have a smartphone or tablet to use it). When you say, “Alexa, ask my buddy for help” the service will send a text, email, and phone call to a list of contacts to let them know they should check in. You can also place a phone call through the Echo to anyone who has the free Amazon Alexa app on their phone. Though the Echo may be the easiest and least expensive device to fit into your lifestyle, this setup would not be helpful at all in emergencies, and only marginally helpful in nonemergencies. Still, it would be better than nothing. Pull Quote I wouldn’t want a loved one of mine counting on any medical alert alone to keep them safe, but especially not the Echo. There’s nothing to remember to wear or charge, and the device doesn’t look anything like a medical device because it’s not. You’ll get all the other capabilities of the Echo (here’s our full guide), and at $180, it costs less than four months’ worth of service with a traditional medical alert company. Unlike other services, this one can’t connect you to 911 directly or via a call center or confirm that someone received your request. The range is small; the feature works reliably only if you’re in the same room as the Echo (that said, multiple Echos or Echo Dots can all be linked together to cover many rooms or a larger home). As such, Ask My Buddy should be treated only as an additional tool for a little added peace of mind in addition to thoughtful design of a home around the person using it. I wouldn’t want a loved one of mine counting on any medical alert alone to keep them safe, but especially not the Echo. We think that the Echo will be the best device to pair with Ask My Buddy for most people, though it also works with other Amazon Alexa devices and Google Home (our full guide). The Echo indicates that it heard you with a ring of light at the top of the device, and it’s taller than Google Home (which has a slanted face with indicator lights) and other Alexa options, making it easier to see from across the room. Ask My Buddy was a little easier to set up and use on the Echo than on Google Home (you’ll still need a little app savvy, or have someone around who does, as you’ll need to connect the device to a smartphone and Wi-Fi). The range on any voice-controlled device is smaller than that of a home medical alert system with a base station. When I tried screaming “Hey, Alexa” over and over from a room away while the dishwasher was running, it didn’t pick up my voice. The sound quality on either end of the phone call placed through the Alexa wasn’t as good as it is on a traditional medical alert device. Though you may run into range problems with a home medical alert with a base station, it’s easier to get someone on the line (you just push a button), at which point, they’d at least know that you needed help even if you were unable to communicate; the same can’t be said of a call that’s not picked up or a text that goes unseen. Another concern we have about Ask My Buddy: It’s a free app run by volunteers. There’s no guarantee that it’s sticking around, and you can’t contact people otherwise through an Echo. There’s an email to send issues and questions to, but you can’t get in touch with a representative right away if you run into a problem with its service. Amazon does have a customer service line to help with Echo setup. Amazon’s Echo Connect, launched in September 2017, is the first Echo device with phone calling capabilities (rather than just Echo-to-Echo intercom communication). You can use it to call any landline, including 911 calls. It also has built-in speakerphone and caller ID features. We are looking into the possibility of using the Echo Connect as a medical alert system, and if we think it’s a better option than an Echo paired with Ask My Buddy we’ll update this section with our thoughts. What to ask in a test call For medical alerts that come with a monitoring service, experts recommend pushing the button on your medical alert at least once a month to confirm that it’s working well. This step is especially important when you first start using your medical alert. Pushing the button should feel like second nature during a true emergency. One participant in the University of Western Ontario focus group recalled forgetting about the device during a heart attack: “The button didn’t even come into my mind. All I knew I was in trouble.” Plus, you need to make sure that the device works the way you think it does. Aunt Kay fell outside her house, and, thinking she had a mobile system, pushed the button to call for help to no avail. Though she was able to crawl to her car to retrieve her cell phone, the incident left her and our family shaken. It’s scary to find out you don’t have help at the ready when you think you do. Through expert advice, and some trial and error, I learned that there are a few things that I’d want my loved ones doing during a test call to ensure that their device is working properly. Confirm that the company has your correct home address on file. In particular, if the device was shipped to another location, this could be wrong—and cause problems if you fall and say you’re at home. Ask the operator if they can tell you where you are right now. If they are off by more than a block, call customer service. In one case during my tests, the GPS wasn’t working at all, a problem that might not have come to light if I hadn’t asked about it. Again, in another case, when I called from my home in Brooklyn, the operator informed me that I was at the New York Times Building, in midtown Manhattan. If you think you have automatic fall detection, confirm that this is the case with the operator. Many devices will announce that they are activating automatic fall detection when you first plug them in, even if this feature isn’t something you are paying for and therefore won’t be able to use. If you do have automatic fall detection, do a test fall by dropping the device on the ground. I also learned that the agents at the call center are typically not able to help you troubleshoot any issues that the device itself is having. If you learn during a test call that anything is amiss, you’ll need to hang up and call customer service. Why we don’t recommend Life Alert We quickly eliminated Life Alert—the brand so ubiquitous it’s name is often used to describe medical alerts in general—from the running. The company requires users to sign a 36-month contract that can be broken only if you go into 24/7 care or die. That’s a dealbreaker because it’s hard to know if a particular medical alert (or any medical alert at all) is something you’ll use until you try it out. The ability to cancel your service with minimal penalties is key to a good medical alert. Beyond that, Life Alert’s marketing is aggressive, making perusing its products annoying at best. There are outsized claims about its products’ lifesaving abilities on the website, but minimal information on the devices themselves. When I called the customer service line for more information, a representative immediately asked for my address. As I asked questions about the service, a rep encouraged me to give my mom “the gift of life”—meaning its product—for Mother’s Day. The competition Our former runner-up pick, the Medical Guardian Premium Guardian, is no longer available. Medical Guardian now offers a different device, the Active Guardian instead. We tried this device, and don’t like it enough to recommend it as a pick, though if you don’t care about looks and are better covered in your area by AT&T service (as opposed to Verizon) it’s a fine choice.
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www.forbes.com www.forbes.com
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Most people think of loyalty programs as an airline that gives miles to frequent fliers, a hotel that gives points toward a stay or a restaurant that offers a punch card incentive. While these may be called loyalty programs, I’ll argue that they are actually marketing programs disguised as loyalty programs. And while I don’t have a problem with this concept, we need to have a clear understanding of the differences between loyalty and marketing.
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www.lancaster.ac.uk www.lancaster.ac.uk
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Barry proposesaview of inventiveness as “an index of the degree to which an object or practice isassociated withopening upquestions and possibilities ... what is inventive is not thenovelty of artefacts in themselves, but the novelty of the arrangements with other activitiesand entities within which artefacts are situated. And might be situated in the future” (p. 4).He suggests further that there might actually be an inverse relation between the speedofchange, and the expansion of inventiveness– that “moving things rapidly may increase ageneral state of inertia; fixing things in place before alternatives have the chance ofdeveloping” (p. 6). I have made a similar argument (Suchman 1999)with respect totechnology innovation under the banner of ‘artful integration,’ attemptingto shift the frameof design practice and its objects from the figure of the heroic designer and associated nextnew thing, to ongoing, collective practices of sociomaterial configuration, andreconfiguration in use.
I think this is an important point, that relates to a statement from the Acceleration manifesto:
- Given the enslavement of technoscience to capitalist objectives (especially since the late 1970s) we surely do not yet know what a modern technosocial body can do. Who amongst us fully recognizes what untapped potentials await in the technology which has already been developed? Our wager is that the true transformative potentials of much of our technological and scientific research remain unexploited, filled with presently redundant features (or pre-adaptations) that, following a shift beyond the short-sighted capitalist socius, can become decisive.
http://criticallegalthinking.com/2013/05/14/accelerate-manifesto-for-an-accelerationist-politics/
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murmurations-journal.org murmurations-journal.org
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Wewant to find out what it is that each child can be passionate about and then how they cancontribute hopefully later on in life. We want to guide them into being good people
This ending quote as well as the discussion in the paper introduction make me think of frameworks for the goals of public education, which often identify primary goals of “good people,” “good citizens,” and “good workers.” There’s a strong urging in this manuscript to shift emphasis away from “good workers” and toward the personal growth and community health goals learning. There’s also a historical perspective that may be worth considering here, as the way society views the primary goals of education has shifted back and forth over time. As Cohen and Malin (2010) note, “People have been worrying about the purposes of education for at least 2,500 years, from the times of the Buddha, Confucius, and Plato until today.”
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murmurations-journal.org murmurations-journal.org
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What questions am I left with? What would I like to know more about?
There are a two questions that immediately spring to mind upon engaging with this article: First, I wonder, do engineers understand quite how deep the problem goes? Second, while I believe the solution to the problem is really quite simple, I am curious whether most Engineers would be willing to embrace it. I will now address each of these questions in turn.
Do Engineers understand quite how deep the problem goes?
There is now an overwhelming body of evidence which indicates that evolution engineered the brain to put analytic and empathic thinking into tension. Scientific and mechanical reasoning, along with calculation (math) and logic, are prototypical types of analytic thinking. When we engage in these types of thinking, we shut down the brain areas we need to understand the perspective of others (Anticevic et al., 2012; Jack et al., 2012) – an absolutely crucial component of ethical awareness and deliberation (Friedman & Jack, 2017; Jack, Dawson, & Norr, 2013).
My main critique of this discussion article relates to the fact that the authors only touch on the surface of the large body of evidence which not only supports this view of the brain, but which also indicates that it impacts human behavior. First, the authors appear to have overlooked other work from my laboratory which is supportive of this view (e.g. a follow up study of the neural basis of dehumanizing (Jack et al., 2013)My laboratory has focused on this issue and its behavioral consequences for many years now. However, it would be very concerning if such claims about the function of the brain were wholly dependent on work from a single laboratory! Happily, this is not the case. The fact that attention demanding analytic tasks, such as mechanical reasoning, tend to deactivate brain regions essential for social, emotional and moral cognition might be fairly characterized as one of the most clearly established findings in cognitive neuroscience (Anticevic et al., 2012; Buckner, Andrews-Hanna, & Schacter, 2008; Shulman et al., 1997)]. This work is broken down in greater detail in many of my more recent articles. In addition, there are behavioral studies by researchers with no interest in the brain which clearly show that analytic thinking negatively impacts ethical thinking and behavior (Small, Loewenstein, & Slovic, 2007; Wang, Zhong, & Murnighan, 2014; Zhong, 2011)
These studies provide powerful convergent evidence, since they were in no way motivated or informed by neuroscience – they are observations about patterns of human behavior made by behavioral economists and psychologists without reference to the underlying neural mechanism which explains why they occur. Since the authors do not appear to be aware of much of this literature, large parts of the article are quite tentative in tone. Nonetheless, in the section titled “Reflections on the implications for learning engineering”, the authors provide an excellent and incisive summary of exactly why our understanding of the brain should be a serious cause for concern for those who are concerned about educating ethical engineers.
In this regard, it is worth mentioning how an emphasis on analytic thinking might increase one’s ability to ‘rationalize away’ the ethical consequences of one’s decision(s). The sorts of problem solving skills that engineers learn might then be applied to social and ethical dilemmas, which in turn removes the social and ethical significance.
The authors do an excellent job of discussing why an engineering education is likely to reinforce students into predominately relying upon analytic thinking in preference to empathic thinking. They do this using the model shown in Figure 4, which illustrates how doing/behavior (i.e. practice at particular types of task) enables changes in structure (neural network function), and also vice-versa: changes in structure enable changes in doing/behavior. This creates a cycle of reinforcement. As the authors nicely put it: “the ‘doing’ that activates the Physical Stance [i.e. an engineering education] gives rise to the Physical stance as a preferred, low activation cognitive pathway….condition[ing] people to unconsciously apply mechanical reasoning to situations where social or moral reasoning would be a better fit for the purpose.” I believe the authors are exactly on point with this model. In my laboratory we have extended our neuroscience work by also measuring individual tendencies to think analytically and empathically with simple behavioral tests and self-report questionnaires. One way in which we measure analytic thinking is using the Intuitive Physics Test developed by Simon Baron-Cohen and colleagues, which can be easily found online for those who are interested and which is a good measure of everyday aptitude for mechanical thinking (Baron-Cohen, Wheelwright, Spong, Scahill, & Lawson, 2001)
In these purely behavioral tests, we consistently find evidence for a small trade-off between these two ways of thinking (Friedman & Jack, 2017). That is, individuals who score higher on analytic thinking tend to score very slightly lower on empathic thinking. Some of these findings are reported incidentally in (Jack, Friedman, Boyatzis, & Taylor, 2016). We are currently preparing a manuscript which collates a much larger set of studies and focuses solely on this issue. The small trade-off between empathic and analytic thinking becomes accentuated for cases where it is less clear which way of thinking is best suited to the matter of hand. For instance, we have now performed a number of studies of religious belief. Supernatural claims, such as that God or a universal spirit exists, seem clearly incorrect from a purely mechanical way of thinking. However, we posited that they would seem correct from an empathic way of thinking. Correspondingly, we found that analytic thinking ability is associated with decreased religious belief, whereas empathic thinking is associated with increased religious belief (Jack et al., 2016). Other unpublished work in progress shows an even more robust association between these two ways of thinking and how much individuals care about dehumanized outgroups. Unsurprisingly, people higher in empathy care more about dehumanized outgroups than people lower in empathy. More remarkably, people who score higher on the Intuitive Physics Test care less about dehumanized outgroups than people who score lower on that measure of analytic thinking. I am comfortable informally reporting this finding since we have now replicated it. We aim to extend it with a further study before publication. The important point which emerges from this work is that individuals who have strongly reinforced one way of thinking without seeking to balance that out with another way of thinking show a clear tendency to default to (or prefer) one cognitive strategy over another when faced with any situation which is even remotely ambiguous. In other words, those whose training has focused predominantly on analytic thinking, such as engineers, will tend to overlook the more human perspective. This observation was made anecdotally long before cognitive neuroscience emerged as a discipline, or psychology developed the instruments to assess it quantitatively. The famous Oxford philosopher, P.F. Strawson, wrote in his groundbreaking article on the philosophy of free will “But what is above all interesting is the tension there is, in us, …between our humanity and our intelligence” (Strawson 1962, p.10).
In the next part of their section titled “Reflections on the implications for learning engineering,” the authors make another insightful and important point. They observe that as we overdevelop one way of thinking, we may distort our whole picture of the world to fit with that way of thinking. They make this point by reference to Lakoff’s notion of frames, which is certainly a useful tool for thinking about how we think. However, I would suggest the basic point is perhaps more simply and more powerfully made by the well-known aphorism they aptly mention: “If one only has a hammer, everything looks like a nail.”
The distortion of the world to fit with a purely scientific or analytic way of thinking is something I find I am obliged to wrestle with frequently. One label for this phenomenon is ‘scientism’. Since I teach at university dominated by the hard sciences and Engineering, such scientistic attitudes are quite common. They are also quite common in neuroscience and in some branches of psychology. An amusing example of this is a recent book by the very analytically smart psychologist Paul Bloom, who has written many warmly received popular science books. However, he recently published a book titled “Against Empathy” to resounding condemnation from virtually all intellectually informed readers, in particular other psychologists, philosophers, sociologists and anthropologists. In essence, Paul Bloom’s lack of connection to empathy motivated him to form a completely distorted picture of it, and motivated him to write a book which attacks empathy in ridiculous and contrived ways, such that it is barely coherent from an analytic (either scientific or logical) point of view. Such poor judgment is remarkable for such a smart and accomplished individual, both as a scientist and as a popular science author.
Since the discussion article highlights the tension between mechanistic reasoning and ethics, it is important to note that ethics itself can be split into perspectives that are predominantly analytic (utilitarianism), versus more empathic perspectives that focus more on humanity. This is in itself a topic of some study in cognitive neuroscience. My own published view is that competent ethical thinking requires us to balance analytic and empathic perspectives on a situation (Friedman, Jack, Rochford, & Boyatzis, 2015; Friedman & Jack, 2017; Rochford, Jack, Boyatzis, & French, 2016). In general, the error that is most often made in current society is to tend towards emphasizing an analytic approach and excluding an empathic approach. That a purely analytic way of thinking ethically is problematic is illustrated by the fact it motivates actions without regard for human rights, including acts which would be categorized under current law as unjustified killing. Many of the recent ethical scandals that have plagued major corporations appear to have stemmed from an overemphasis on an analytic way seeing issues. An analytic, performance oriented way of thinking, especially in organizations, can have more subtle ethical consequences, such that those individuals are less likely to engage in helpful behaviors that bolster the social atmosphere at that organization (Bergeron, 2007; Bergeron, Shipp, Rosen, & Furst, 2011).
While a solution may be straightforward, would most engineers be willing to embrace such a solution?
There is one way in which the problem may not be quite so bad as the authors fear. They suggest that a focus on mechanical reasoning may actively weaken our social and ethical thinking skills. This is one way of reading what the neuroscience tells us, however I would suggest another way of understanding it. The fact that social, emotional and moral cognition areas are suppressed during mechanical reasoning need not mean they are being weakened. Another way of looking at this suppression is that it is protective – it gets those brain areas out of the way. In any case, there is no reason to suppose the suppression actively weakens the function of those brain areas. It merely fails to develop them. This is a problem which, I suggest, can be overcome by two strategies: (1) training to ensure the empathic, as opposed to the analytic brain network, is deployed during social and ethical decision making and (2) training to develop the empathic brain network. Neither of these strategies need impugn the intention to predominantly train engineering students in mechanical reasoning. They merely require engineering schools to embrace and positively require a modest number of courses which can help stem one side of their students brains’ from withering away. Training of the empathic network may be accomplished by classes on empathic listening, social skills for leadership, art appreciation, history, literature, as well as philosophy classes on happiness and ethics. Such classes are likely to greatly help students to possess more balanced brains and live more balanced lives. As a result they are likely to improve student performance, rather than detract from their engineering skills. My concern, however, is that many professional engineers are likely to be so unfamiliar with these forms of understanding, that they will find it hard to endorse including them in the curriculum. Indeed, some engineering faculty may be so unfamiliar with the value of these types of thinking that they find them threatening, and so react by being dismissive and actively fighting their introduction in the curriculum. In other words, they might be ‘blind’ to the value of such social, ethical and moral insights because they lack they the cognitive ability to perceive them, let alone appreciate them. Hence, while there may be many enlightened Engineering faculty, such as those who have written this discussion piece, I suspect a different voice will triumph in faculty meetings. If psychology has taught us anything, it is that human decision making is rarely guided by passion for the truth as much as by other emotions, especially emotions associated with a sense of threat to self. Hence, while it may be that no reasonable person could deny the brain has been engineered by evolution such that it needs to be educated in different modalities, I rather doubt this truth will guide engineering faculty.
I'd like to acknowledge Jared Friedman for thoughtful input to the reflections that I offer here.
Anticevic, A., Cole, M. W., Murray, J. D., Corlett, P. R., Wang, X. J., & Krystal, J. H. (2012). The role of default network deactivation in cognition and disease. Trends Cogn Sci, 16(12), 584-592. doi:10.1016/j.tics.2012.10.008 S1364-6613(12)00244-6 [pii]
Baron-Cohen, S., Wheelwright, S., Spong, A., Scahill, V., & Lawson, J. (2001). Are intuitive physics and intuitive psychology independent? A test with children with Asperger Syndrome. Journal of Developmental and Learning Disorders, 5(1), 47-78.
Bergeron, D. M. (2007). The potential paradox of organizational citizenship behavior: Good citizens at what cost? Academy of Management Review, 32(4), 1078-1095. Bergeron, D. M., Shipp, A. J., Rosen, B., & Furst, S. A. (2011). Organizational citizenship behavior and career outcomes the cost of being a good citizen. Journal of Management, 0149206311407508.
Buckner, R. L., Andrews-Hanna, J. R., & Schacter, D. L. (2008). The Brain's Default Network: Anatomy, Function, and Relevance to Disease. Annals of the New York Academy of Sciences, 1124(1), 1-38. doi:10.1196/annals.1440.011 Cech, E. A. (2014). Culture of disengagement in engineering education? Science, Technology, & Human Values, 39(1), 42-72.
Friedman, J., Jack, A. I., Rochford, K., & Boyatzis, R. (2015). Antagonistic Neural Networks Underlying Organizational Behavior. Organizational Neuroscience (Monographs in Leadership and Management, Volume 7) Emerald Group Publishing Limited, 7, 115-141.
Friedman, J. P., & Jack, A. I. (2017). Mapping cognitive structure onto the landscape of philosophical debate: An empirical framework with relevance to problems of consciousness, free will and ethics. Review of Philosophy and Psychology.
Jack, Dawson, A. J., Begany, K. L., Leckie, R. L., Barry, K. P., Ciccia, A. H., & Snyder, A. Z. (2012). fMRI reveals reciprocal inhibition between social and physical cognitive domains. Neuroimage, 66C, 385-401. doi:S1053-8119(12)01064-6 [pii] 10.1016/j.neuroimage.2012.10.061
Jack, Dawson, A. J., & Norr, M. E. (2013). Seeing human: distinct and overlapping neural signatures associated with two forms of dehumanization. Neuroimage, 79, 313-328. Jack, A. I., Friedman, J. P., Boyatzis, R. E., & Taylor, S. N. (2016). Why do you believe in God? Relationships between religious belief, analytic thinking, mentalizing and moral concern. PloS one, 11(3), e0149989.
Rochford, K. C., Jack, A. I., Boyatzis, R. E., & French, S. E. (2016). Ethical leadership as a balance between opposing neural networks. Journal of Business Ethics, 1-16.
Shulman, G. L., Fiez, J. A., Corbetta, M., Buckner, R. L., Miezin, F. M., Raichle, M. E., & Petersen, S. E. (1997). Common Blood Flow Changes across Visual Tasks: II. Decreases in Cerebral Cortex. J Cogn Neurosci, 9(5), 648-663. doi:10.1162/jocn.1997.9.5.648
Small, D. A., Loewenstein, G., & Slovic, P. (2007). Sympathy and callousness: The impact of deliberative thought on donations to identifiable and statistical victims. Organizational Behavior and Human Decision Processes, 102(2), 143-153. doi:10.1016/j.obhdp.2006.01.005
Wang, L., Zhong, C.-B., & Murnighan, J. K. (2014). The social and ethical consequences of a calculative mindset. Organizational Behavior and Human Decision Processes, 125(1), 39-49.
Zhong, C.-B. (2011). The ethical dangers of deliberative decision making. Administrative Science Quarterly, 56(1), 1-25.
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lorraine-chuen-e9f3.squarespace.com lorraine-chuen-e9f3.squarespace.comHome1
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We provide strategic support on how they can most effectively make their data openly available and useful.
i think we may have never done copy on this...
it sounds a bit generic and maybe not that useful, nor actually tied to our mission - maybe something on building infrastructure (like policies, practices, and culture) around open government...for gov't to better publish and mobilise their data and information assets
also maybe we should be more general than data - we have been doing alot around information as well.
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www.theatlantic.com www.theatlantic.com
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the creative aspect of thinking is concerned only with the selection of the data
creative thinking selection
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murmurations-journal.org murmurations-journal.org
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We rarely heard a teacher praise a student; he or she is more likely to make a comment thatreflects a factual observation and recognizes the student’s effort, such as “you took a lot of timewith that drawing.” This is the kind of comment that is now recognized as supporting a growthmindset and contributing to student success. Even
how much back ground should be included? I notice my own discomfort about wanting the article to fit within a more traditional paper. I am wanting a reference on mindset, and felt the same on the market-based education model. I think it may be worth citing major sources so if people would like to read more, they can know where to start.
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www.seethingbrains.com www.seethingbrains.com
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He kills her in her own humour.
Spoken by Peter, one of Petruchio’s servants, this line serves as a turning point in the attitude of the reader as well as the servants present during Act IV Scene 1. Following the wedding, Petruchio brings Kate home and begins slandering his servants, and the reader is left confused and wondering where this shift in demeanor is coming from. Prior to meeting Kate, Petruchio comes off as intelligent, outgoing, and strong willed but is now widely regarded as mean and unforgiving. As Petruchio acts out, this line provides a brief explanation of the intention of his actions. He was aware of Kate’s reputation and shrewish behavior before marrying her, thus concocting a plan for how to “tame” her, yet the solution is unbeknownst to the reader. As Peter concludes, Petruchio essentially hoped to give her a taste of her own medicine all along. Shakespeare’s choice of the word “humour” is indicative of the irony in the situation. Though one of the denotations of humour is temperament, we can almost take it as comical. She may think her behavior is amusing, but in reality it is her biggest flaw. Petruchio lashing out to his servants and creating a fuss about everything is reflective of Kate’s own conduct. As we read through the scene, we are almost worried about the change in dynamic, but all of this is gone once we understand that it is an act; Petruchio simply means to show her that the torture he is putting her and his servants through is not dissimilar to her own actions.
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doc-08-7c-docs.googleusercontent.com doc-08-7c-docs.googleusercontent.com
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Our review of the literature indicates that parental participation in schools is strongly shaped by perceptions of parents’ background and of the roles expected of them by school administrators and teachers and by the organizations (whether local or federal) that fund family literacy and parent involve-ment programs
This reminds me of our work we did with unintentional bias in our social foundations course. We have so many biases that come through in our everyday practice as educators that may come through without our knowledge. In the case of family involvement in the school, I think as educators who understand and value the importance of family involvement, it is our job to encourage participation and help the family's come in, whether or not we have a bias as to if they can or want to come into the classroom.
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We think that an examination of these tropes could be useful for teachers and other professionals to critically assess the goals of programs and initiatives and the effects that they might have in creating inclusive or dismissive roles for parents. Although “antideficit rhetoric” is common-place in contemporary parent involvement program models (e.g., the ubiquitous use of a discourse of “strengths”), E. Auerbach (1995) warns that this shift may operate as a neodeficit ideology in which even “strength-based” program models could continue to function within a deficit framework.
Yes, this is crucial. We must be self-reflective and think critically about the ideologies we are asked to engage in as educators. So many of the boxed curriculum, or boxed diversity/ engagement models use language that would appear to indicate an understanding of these tropes, thereby rejecting a deficit view/ model are actually perpetuating deficit thinking. I appreciate the authors' term "neodeficit ideology."
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Lareau and Horvat (1999) report on a study of school–home relations across class statuses showing how particular forms of social capital used by low-income African American parents were rejected by school personnel who dismissed critique and only accepted praise. In contrast, White parents, who began their relationships with the school from a more trusting stance (given also their less-problematic framings in the history of U.S. education) were welcomed to class-rooms. Middle-class African American parents were able to negotiate their relation-ships with teachers by hiding concerns about racial discrimination while staying actively involved and alert. Howard and Reynolds (2008) urge us to consider the variability within middle-class African American parents; in spite of their economic position, some parents still experience racist attitudes as they advocate for their children and other parents may be reluctant to engage in the already set structures of predominantly White middle-class school settings
I chose this section of the article because it stood out to me. As I reflected on what it meant for parents to have to hide their concerns because of the way the school would treat them, I started to think about the conversations of biases. This is almost in a way "a dream within a dream", we come into school as educators already having some set biases and then work at a school where the other educators have their own biases, and then the administration has their own biases and then it continues down the line. We are conditioned to then view parents as difficult or easy going based one our experiences with other parents. Since we enjoy putting people in categories, we then find ourselves meeting new parents and maybe thinking, "Wow, they remind me of Sara's mom, she seems so nice." It shocks me that schools would even begin the school year already knowing and rejecting some parents' opinions because they base them on the their view of the parents race, class, or race and class.
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doc-14-6k-docs.googleusercontent.com doc-14-6k-docs.googleusercontent.com
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He writes, “Faith in people is an a priorirequirement for dialogue; the ‘dialogical person’ believes in others even before he meets them face to face” (pp. 90-91). In Pedagogy of Freedom, Freire (1998) reiterates the importance of leaders’ faith in the people: “On no account may I make little of or ignore in my contact with such groups the knowledge they acquire from direct experience and out of which they live” (p. 76).
I completely agree with this statement and how it relates to Freire's concept of "dialogical love." I think it is of utmost importance to have faith in people, and give them opportunities just like you would any other. The only thing that creates some dissonance with me is that this seems so easy to do theoretically, but really very hard to put into practice. When I was reading this, I thought back to our discussions in Social Foundations surrounding unconscious biases and how they are frequently present in our daily interactions with others without even realizing it. Our society perpetuates these biases, stereotypes, and generalizations towards people that cause us to not have faith in people or believe in them before we even meet them as Freire states. Our society, as well as how our brains are wired, are based on forming generalizations and categorizing people or groups. This is why, although I completely agree with Freire's statement, I think it is more theoretical than practical.
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Therefore, with such humility and faith, dialogue centers the contextual expertise of the people as active advocates for social transformation. This is done for both moral and pragmatic reasons as, from Freire’s perspective, the oppressed deserve such humane engagement, but—more importantly—they are uniquely experienced and strategically positioned to instigate authentic change directed at widespread humanization.
After reading a lot of Freire in our Social Foundations class I noticed him mentioning the importance of dialogue and how we have to do it often. When we choose to sit back and not talk about issues or things we notice or make us uncomfortable, we are allowing these situations to keep happening. I appreciate the author saying that the oppressed has experiences that most people will not be able to talk about it, and that they should have the floor to speak freely and allow connections to happen. I recently picked up a book that is a large set of letters written by trans women to other women transitioning. I have had many friends transition and knowing that some of my friends may identify with my gender, but in my case I don't have the perspective of transitioning. I thought the book was such a gift to women transitioning to hear from other women that went through the same thing. I think when we start to speak up or understand what we can add and what we can support, then we become active advocates.
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Why do we put so much of our attention and resources into trying to fix what goes on inside low-performing schools when the causes of low performance may reside outside of the school? Is it possible that we might be better off devoting more of our attention and resources than we now do toward helping the families in the communities that are served by those schools (p. 963)
Yes. I feel like this all the time. I did Americorps and one of my projects was teaching in an elementary school in Brownsville, Brooklyn and then setting up and facilitating an after school program for the children that attended the school I taught at and lived in the same project complex as me and my team members. It became very apparent to me that year that the community had so much to offer that was not being utilized and all the conversation about education inside of the school walls was about deficits and lack as they were constantly in a struggle to follow state and federal guidelines that did not make room for the unique offerings and challenges of the neighborhood. Home and school were very much attempted to be kept separate and the families were rarely asked to engage except on the occasion that problems arose.The after school program was meant to address these family-school life gaps. Additionally, I think the demand on teachers is far too high, as we talked about in class with Maslow's hierarchy; food, clothing and a safe home environment need to be met before learning can take place. This tends to fall on teachers when students are "underperforming" but we forget that our society has failed the children first by not ensuring basic needs have been met. In terms of dialogic love, Freire is clear that each of us is unfinished, meaning there is still more to learn. This learning occurs in our encounters with others. If we are open to the "funds of knowledge" of others, even when they conflict, we can actually create community in a way that deeply supports children's development and growth. This requires not only active listening, but I think a desire to seek connections in places that are usually not connected, making children feel whole in their lives, rather than compartmentalizing school and home.
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press.rebus.community press.rebus.community
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If students are living their lives in preparation for life, when will they start living? When do rules and regulations pay off? The answer is never. If students aren’t free to be curious, engaged, and invested in what they’re learning, then they may never be curious, engaged, or invested in their lives. Education is about more than passing a test or being accepted to the “right” school, it’s about self-discovery and personal growth as an individual.
Woah. That's really interesting to think about how we just continually just prep for the future.
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theorizingtheweb.org theorizingtheweb.org
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just.
And finally, I wish somebody who had read this book had been in the room:
for myself: I am reading 'the highest poverty'
But Agamben's thesis is that the true novelty of monasticism lies not in the confusion between life and norm, but in the discovery of a new dimension, in which "life" as such, perhaps for the first time, is affirmed in its autonomy, and in which the claim of the "highest poverty" and "use" challenges the law in ways that we must still grapple with today.
How can we think a form-of-life, that is, a human life released from the grip of law, and a use of bodies and of the world that never becomes an appropriation? How can we think life as something not subject to ownership but only for common use?
May be if we learn to tackle our consumption habits we will stop being seduced by the wall-e future on offer by AI.
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- Apr 2018
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wisc.pb.unizin.org wisc.pb.unizin.org
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The jury trial, especially politically considered, is by far the most important feature in the judicial department in a free country, and the right in question is far the most valuable part, and the last that ought to be yielded, of this trial. Juries are constantly and frequently drawn from the body of the people, and freemen of the country; and by holding the jury’s right to return a general verdict in all cases sacred, we secure to the people at large, their just and rightful controul in the judicial department. If the conduct of judges shall be severe and arbitrary, and tend to subvert the laws, and change the forms of government, the jury may check them, by deciding against their opinions and determinations, in similar cases. It is true, the freemen of a country are not always minutely skilled in the laws, but they have common sense in its purity, which seldom or never errs in making and applying laws to the condition of the people, or in determining judicial causes, when stated to them by the parties. The body of the people, principally, bear the burdens of the community; they of right ought to have a controul in its important concerns, both in making and executing the laws, otherwise they may, in a short time, be ruined. Nor is it merely this controul alone we are to attend to; the jury trial brings with it an open and public discussion of all causes, and excludes secret and arbitrary proceedings. This, and the democratic branch in the legislature, as was formerly observed, are the means by which the people are let into the knowledge of public affairs — are enabled to stand as the guardians of each others rights, and to restrain, by regular and legal measures, those who otherwise might infringe upon them.
I like this highlighted passage (I would leave out everything else). In regular sophomore US History, I don't teach them the difference between a civil case and a criminal case (I save that for Law & AP Gov't), but we do talk about the role of juries in our justice system. So, I think this passage is properly placed under the 7th Amendment, but I would use it as a justification for why the jury system exists not just for civil cases but in our justice system as a whole. This passage would be really good at explaining the reason why we have it. It is realistic about how jurors are not experts in the law, but the system still works.
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ccole20.weebly.com ccole20.weebly.com
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I love humor. I think humor is one of the most effective ways to diffuse tension, especially with patients as they have found themselves in a place they may not want to be. I found humor to be an excellent way to diffuse tension throughout all 3 of my fieldworks. I feel confident I have mastered this skill. I found myself using humor with children just as much as I did with older adults. One intervention in particular that I found to create much tension was working on handwriting with pediatrics. Every single one of my kids hated to work on handwriting. I got on Pinterest and researched many different ways to attempt to make it more exciting. One thing I found to diffuse the tension and decease the anger in the patients was to create humor with sentences. By coming up with funny sentences and stories, the kids would laugh, keep better attention, and be anxious to see what the next sentence would be that they were going to write. We would also take turns creating funny sentences. Humor is always a great remedy!
Approved. You used a very good example of how you incorporated humor and it was very appropriate for the setting. Encourage the use of client vs. patient.
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wisc.pb.unizin.org wisc.pb.unizin.org
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And as to the faculties of the mind, setting aside the arts grounded upon words, and especially that skill of proceeding upon general and infallible rules, called science, which very few have and but in few things, as being not a native faculty born with us, nor attained, as prudence, while we look after some what else, I find yet a greater equality amongst men than that of strength. For prudence is but experience, which equal time equally bestows on all men in those things they equally apply themselves unto. That which may perhaps make such equality incredible is but a vain conceit of one’s own wisdom, which almost all men think they have in a greater degree than the vulgar; that is, than all men but themselves, and a few others, whom by fame, or for concurring with themselves, they approve. For such is the nature of men that how so ever they may acknowledge many others to be more witty, or more eloquent or more learned, yet they will hardly believe there be many so wise as themselves; for they see their own wit at hand, and other men’s at a distance. But this proveth rather that men are in that point equal, than unequal. For there is not ordinarily a greater sign of the equal distribution of any thing than that every man is contented with his share.
I might remove this paragraph entirely..... I think students would spend a LOT of time on it, but I am not that would be time well spent. I think it can go from the big idea of equality in the state of nature to how that plays out.
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desktopmag.com.au desktopmag.com.au
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Forty or fifty years ago, the workforce was overwhelmingly a man’s world. In the design field, many women may have been assistants or “office girls” and so few held the top titles, such as art director or creative director. In a basic sense, women’s careers have rarely followed the same path of men’s, since there has historically been immense pressure placed on women to be solely homemakers and nurture families (see: Beyond The Glass Ceiling: an open discussion, Astrid Stavro, Elephant #6) with more sinister pressures of socially-accepted sexism and segregation discouraging, or even disqualifying, the career ambitions of capable women
Unfortunately there is persecution, and I think it still exists, but with some differences, for example, women's salaries are lower than men's salaries so far in many countries. in my opinion it is not fair, Whereas women have talent in many areas and may outperform men.
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www.cambridge.org www.cambridge.org
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Fear of stigma and being discriminated against has continued to be a companion of the HIV pandemic since its outbreak more than 30 years ago, despite significant efforts at individual, community and institutional levels (Holzemer & Uys, 2004; Pulerwitz et al., 2010; Aggleton et al., 2011)
<br>Analytic Note (Source 1): Stigma is still perceived as a major limiting factor in HIV/AIDS prevention and care. HIV/AIDS stigma and discrimination continue to influence people living with and affected by HIV disease as well as their health care providers, wherever they live. This review article discusses HIV/AIDS stigma, the impact of AIDS stigma and how healthcare providers can help to manage HIV/AIDS stigma in South Africa. In defining stigma, authors look into different definitions of stigma by various authors and make particular allusion to Goffman’s definition of stigma as ‘an attribute that is deeply discrediting within a particular social interaction’, as a ‘spoiled social identity’ and ‘a deviation from the attributes considered normal and acceptable by society. On the impact of AIDS stigma, the article gives an insight into the fear of, and the stigma associated with, HIV were significantly related to the HIV-affected person’s decision to not seek timely healthcare services. This article provided a base for our study.
Analytic Note (Source 2): According to the late Jonathan Mann, the former WHO Head of Global Program on AIDS recognized stigma, discrimination, blame, and denial as potentially the most difficult aspects of HIV/AIDS to address. This article summarizes the key contributions of the Horizons stigma research portfolio to describing the drivers of stigma, identifying effective interventions and approaches for reducing stigma in different settings, and improving methods for measuring stigma. Horizons developed and implemented a wide range of activities in collaboration with numerous local and international partners in Africa, Asia, and Latin America. This article is cited to corroborate the existence of stigma and discrimination in different settings including healthcare.
Analytic Note (Source 3): This article reflects on the progress over the last 30 years with respect to older and more emergent forms of education concerning HIV and AIDS. This education includes treatment education, HIV prevention education, and education to encourage positive and supportive community response. The article emphasizes on the careful analysis of different forms of HIV-related education, the consequences, effects and identifying specific effectivity of HIV-related education in order to achieve positive outcomes. The article also discusses new ways of seeing and understanding the need to support processes that “think” ahead of the epidemic. This article does not discuss HIV educational strategies that may reduce stigma and discrimination in healthcare settings in the globalized world. However, this article is relevant, though not the basis of our research, because it highlights the difficulty to provide HIV education to stigmatized and discriminated groups after more than 30 years since the start of the epidemic. Giving the negative social responses to HIV and AIDS, education is vital in contributing to a positive response. Individual and community empowerment are the necessary mechanisms by which social inclusion can be promoted.
Source Excerpt (Source 1): Other researchers have reported that health care personnel knew very little about the potential for HIV contamination in the workplace. In Kuwait, some family doctors knew less than they should have about HIV and looked upon AIDS patients negatively, even in the third decade of the AIDS pandemic. Similarly, AIDS stigma and discrimination continue to influence people living with and affected by HIV disease as well as their health care providers, particularly in southern Africa where the burden of AIDS is so significant. Stigma is perceived as a major limiting factor in primary and secondary HIV/AIDS prevention and care. Similar to the findings of Adebajo, Bamgbala and Oyediran (2003) in Nigeria, the results in Kuwait showed that nurses and laboratory technicians also had negative attitudes toward AIDS patients. Health care workers’ poor attitudes and inadequate care in these anecdotal reports could be related to stigma. This argument was reaffirmed in our study.
Source Excerpt (Source 2): Horizons and partners recognized from the outset that to improve the environment for people with HIV in health-care settings, it was important for management and health providers to acknowledge that stigma exists in their facilities. They found that a participatory approach that included ongoing sharing of data about levels and types of stigma in institutions helped build staff and management support for stigma-reduction activities
Source Excerpt (Source 3): “As we approach the 30th anniversary of the date on which AIDS was first identified, it is salutary to reflect on progress made in tackling the epidemic. This is especially so in relation to education and HIV, a field that is laden with possibilities but one that has in many ways eluded its potential. Despite these difficulties, education in a variety of forms holds the potential to arrest and turn back the three epidemics (Mann, 1987) to which HIV has given rise: (a) the epidemic of AIDS, which has caused untold harm through serious illness and death; (b) the epidemic of HIV, in many ways silent, unseen, and often unknown; and (c) the epidemic of fear, shame and denial that has led people living with HIV to be stigmatized, ostracized, discriminated against, and denied their human rights”.
Full Citation (Source 1): Holzemer, W. L. & Uys, L. R. (2004) Managing AIDS stigma. SAHARA Journal 1(3), 165–174. doi/pdf/10.1080/17290376.2004.9724839
Full Citation (Source 2): Pulerwitz, J., Michaelis, A., Weiss, E., Brown, L. & Mahendra, V. (2010) Reducing HIV-related stigma: lessons learned from Horizons research and programs. Public Health Reports 125(2), 272–281. doi: 10.1177/003335491012500218
Full Citation (Source 3): Aggleton, P., Yankah, E. & Crewe, M. (2011) Education and HIV/AIDS-30 years on. AIDS Education and Prevention 23(6), 495–507DOI: 10.1521/aeap.2011.23.6.495
Annotators
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press.rebus.community press.rebus.community
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In order to understand why so many college students do poorly in the first semester at college, we may need to break the question up into parts and look at study time, social life, living away from home, economic issues, mental health, oppression, and more. Studying these parts will help us get a sense of the overall reasons for the problem.
This makes me think of my interdisciplinary major Holistic Health and Wellness. When an individual is being evaluated for a health issue, there are many factors that may contribute to their health issue. Often times when an unwell individual goes to the doctors only the physical parts of them are being observed. The roots of the problem could arise from the mind and the spirit as well as the body. To ensure overall health all of these parts should be evaluated and cared for.
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swansong.asumh.edu:2337 swansong.asumh.edu:2337
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Building capacity between the private emergency food system and the local food movement: Working toward food justice and sovereignty in the global NorthMcEntee, Jesse C; Naumova, Elena N. Journal of Agriculture, Food Systems, and Community Development; Ithaca Vol. 3, Iss. 1, (Fall 2012): 235-253. 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[[missing key: loadingAnimation]]The full text may take 40-60 seconds to translate; larger documents may take longer.Cancel OverlayEndTurn on search term navigationTurn on search term navigationJump to first hitListen Headnote Abstract One area of food system research that remains overlooked in terms of making urban-rural distinctions explicit is the private emergency food system of food banks, food pantries, soup kitchens, and emergency shelters that exists throughout the United States. This system is an important one for millions of food-insecure individuals and today serves nearly as many individuals as public food assistance. In this article, we present an exploratory case that presents findings from research looking at the private emergency food system of a rural county in northern New England, U.S. Specifically, we examine the history of this national network to contextualize our findings and then discuss possibilities for collaboration between this private system and the local food movement (on behalf of both the public and the state). These collaborations present an opportunity in the short term to improve access to high quality local foods for insecure populations, and in the long term to challenge the systemic income and race-based inequalities that increasingly define the modern food system and are the result of prioritizing market-based reforms that re-create inequality at the local and regional levels. We propose alternatives to these approaches that emphasize the ability to ensure adequate food access for vulnerable populations, as well as the right to define, structure, and control how food is produced beyond food consumerism (i.e., voting with our dollars), but through efforts increasingly aligned with a food sovereignty agenda. Keywords emergency food, food justice, food sovereignty, rural and urban Introduction The rural private emergency food system is an overlooked area of research. The popularity of local food has increased in urban and rural areas alike, yet despite the social and economic capital driving this innovative food movement, foodinsecure populations remain ignored to a large degree. We know that the rural food environment is substantively different than the urban food environment (Sharkey, 2009). People in rural areas generally have less money to spend on food and they live further from markets where local food producers sell their products (Morton & Blanchard, 2007). Producers are predominantly located in rural areas where land and water resources are abundant, yet the most profitable markets for their products more often than not are located in urban centers where they can more easily access a concentrated population center with greater financial capital. These urban-rural distinctions can be made about multiple aspects of food systems research. For instance, early applications of the food desert concept (and the corresponding efforts to identify them) were overwhelmingly situated in urban places. Today, there is recognition that there is not a single food desert definition that can be universally applied. Researchers as well as government authorities have recognized this; for instance, the United States Department of Agriculture (USDA) has adopted different criteria for urban and rural food deserts. In examinations of local food, some have identified key urban-rural distinctions. For example, McEntee's (2010) contemporary and traditional conceptualization has been used to distinguish between a broad base of activities that are local in terms of geographical scale, but potentially exclusive in terms of their social identity and obstacles to adequate access. Access in this sense is not represented by a Cartesian notion of physical proximity, however; it is also indicative of access barriers in terms of financial ability as well as structural and historical (e.g., institutional racism) processes that privilege some, but harm others (McEntee 2011a).1 These concerns are increasingly recognized as part of growing food justice and food sovereignty agendas. The private emergency food system (PEFS) is a national network of food banks, food pantries, soup kitchens, and shelters that operate largely to redistribute food donated by individuals, businesses, and the state. This is a tremendously important system that serves both urban and rural food-insecure populations. Based on a review of this system's functionality, urban-based critiques of this system, and findings from an exploratory qualitative study, we propose that there are key distinctions between the urban and rural PEFSs that have been overlooked (in the same manner that urban and rural local food systems are conflated). The PEFS serves as a safety net for many, yet it struggles financially and lacks access to the high-quality foods (e.g., fresh produce and meat) that clients of this system often prefer. In this article we present emergent opportunities to develop the collaborative capacity between the PEFS and the rural local food system in ways that address the needs of the PEFS and utilize the assets of the burgeoning local food movement. Furthermore, we explain how these synergies potentially contribute to food justice by providing high-quality food to low-income populations. We begin the article with a review of pertinent literatures. This is followed by a depiction of the PEFS, summary of existent critiques, and presentation of our data. We propose that livelihood strategies related to traditional localism (McEntee, 2010) contribute to food justice and food sovereignty agendas by focusing on the natural and social assets of rural communities. We conclude with a discussion of the possibilities for not only remediating the PEFS, but challenging the corporate food regime that currently institutionalizes it. Local Foods, Food Justice, and Food Sovereignty Consumer confidence in the conventional food sector has decreased as a result of food scares (Morgan, Marsden, & Murdoch, 2006), with consumers feeling alienated from modern-day food production (Sims, 2009). From these consumerbased concerns over food safety and a general alienation from modern-day food production, alternative food initiatives and movements have surfaced (including local food initiatives). Feenstra (1997) made the case for local foods as an economically viable alternative to the global industrial system by providing specific steps to be taken by citizens to facilitate the transition between the local and the global; it is these forces that have become the focus of food provisioning studies (Winter, 2003). These efforts include more sustainable farming methods, fair trade, and food and farming education, among others; these have been reviewed extensively elsewhere, such as by Kloppenburg, Lezberg, De Master, Stevenson, and Hendrickson (2000) and Allen, FitzSimmons, Goodman, and Warner (2003). Essentially, all are categorized by a desire to create socially just, economically viable, and environmentally sustainable food systems (Allen et al., 2003) and the majority are now collectively referred to as the dominant food movement narrative (Alkon & Agyeman, 2011). It is from this narrative that the local food movement emerges. Food justice efforts have successfully utilized food localization efforts to improve food access opportunities for low-income and minority communities. These efforts typically occur in urban areas and target low-income minority populations (Alkon & Norgaard, 2009; Gottlieb and Joshi 2010; Wekerle, 2004; Welsh & MacRae, 1998). The concept of food justice supports the notion that people should not be viewed as consumers, but as citizens (Levkoe, 2006); by linking low-income and minority populations with alternative modes of food production and consumption, advocates prioritize human well-being above profit and alongside democratic and social justice values (Welsh & MacRae, 1998). This represents "more than a name change" departure from conventional food security concerns; it is rather a systemic transformation that alters people's involvement in food production and consumption (Wekerle, 2004, p. 379). Increasingly substantiated by racial and income-based exclusion, food justice operates to prioritize just production, distribution, and access to food within the communities being impacted. This is the focus of the food justice movement, though environmental and economic benefits often result from these efforts as well. A recently published volume edited by Alkon and Agyeman (2011) unpacks various forms of food justice, ranging from issues of production (e.g., farmworker rights) to distribution, consumption, and access. In this article we are concerned with the consumption element of the food chain; food justice efforts in this realm often take the form of alternative food initiatives that create new market-based or charity-based solutions to inadequate food access (e.g., farm-to-school programming that link schools and local farmers, slidingscale payment plans for low-income consumers at farmers' markets that are subsidized by wealthier patrons, or agricultural gleaning programs) that stress social equity and solutions that are implemented by and for the people impacted by inadequate access to food. This latter element is a definitive characteristic of food justice initiatives. Most recently, Alkon and Mares (2012) situated food justice in relation to food sovereignty, finding that although food justice and community food security frameworks often challenge conventional agricultural and food marketing systems, the food sovereignty framework is the only one to explicitly underscore "direct opposition to the corporate food regime" (p. 348). This is because both contemporary food justice and (community) food security frameworks often operate within traditional markets that are agents of the industrial agricultural system representative of a neoliberal political economy. This marks a departure between food justice and food sovereignty; La Via Campesina, a major proponent of food sovereignty, defines the concept as: the right of peoples to healthy and culturally appropriate food produced through sustainable methods and their right to define their own food and agriculture systems. It develops a model of small scale sustainable production benefiting communities and their environment. It puts the aspirations, needs and livelihoods of those who produce, distribute and consume food at the heart of food systems and policies rather than the demands of markets and corporations. (La Via Campesina, 2011, para. 2) Whereas food justice often works to create solutions in sync with market structures by filling the gaps in government services, food sovereignty focuses on dismantling the corporate food regime. History and Structure of the PEFS An area of the food system where food justice advocates have increasingly engaged in an urban setting is the PEFS. Operating on a charity basis, emergency food assistance provides food to individuals whose earnings, assets, and social insurance options have not met their needs (Wu & Eamon, 2007). Public government-run assistance programs include welfare, the Supplemental Nutrition Assistance Program (SNAP), Medicaid, and subsidized housing. Private emergency food assistance is provided by nonprofit organizations and includes soup kitchens, food pantries, food banks, food rescue operations (Poppendieck, 1998), and "emergency shelters serving short-term residents" (emphasis added) (Feeding America, 2010a, p. 1). Largely in reaction to dissatisfaction with the federal food stamp program, Congress passed the Omnibus Budget Reconciliation Act in 1982. This act allowed federally owned surplus commodity food to be distributed by the government for free to needy populations. Prior to its passage, the vast majority of food assistance in the U.S. was governmentally provided through the food stamp program (now the Supplemental Nutrition Assistance Program [SNAP]) and the majority of food that food pantries received came from individuals and businesses. The act's success was followed by the Temporary Emergency Food Assistance Act (TEFAP) in 1983, which began the process of routinely distributing excess commodities through private emergency food programs, such as food banks and food pantries (Daponte & Bade, 2006). Food pantries flourished as a result of commoditysourcing, since they now began receiving a reliable stream of food. Businesses that previously did not want to be involved in emergency food provisioning activities could now dispose of unwanted inventory for a much cheaper rate by giving it away (Daponte & Bade, 2006) (see figure 1). In fiscal year 2009, Congress appropriated USD299.5 million for the program, made up of USD250 million for food purchases and USD49.5 million for administrative support (USDA FNS, 2010). In the U.S., companies defined as C corporations by tax code (the majority of U.S. companies) can collect an enhanced tax deduction for donating surplus property, including food. Thus when food businesses donate food to a charity, including food banks and pantries, the businesses can take a deduction equal to 50 percent of the donated food's appreciated value. In addition, the Bill Emerson Good Samaritan Food Donation Act of 1996 provides safeguards for entities donating food and groceries to charitable organizations by minimizing the risk of legal action against donors. Companies are not required to publicly disclose deductions for food donations, though in 2001 corporations wrote offUSD10.7 billion in deductions (Alexander, 2003). Feeding America received USD663,603,071 in charitable donations in 2006. In a 2003 Chicago Tribune article, Delroy Alexander described how America's Second Harvest received USD450 million in donated provisions in 2001, USD210 million of which came from just 10 major food companies, such as Kraft, Coca-Cola, General Mills, ConAgra Foods, Pfizer, and Tropicana (Alexander, 2003). The top five donors each gave more than USD20 million in food, with the top contributor at USD38 million. Current figures are unavailable, though many companies proudly display pounds of food donated on their websites. For instance, Walmart's website states: From November 2008 to November 2009, the Walmart stores and Sam's Club locations have already donated more than 90 million pounds [41,000,000 kg] of food....By giving nutritious produce, meat, and other groceries, we've become Feeding America's largest food donor. (Walmart, 2010) This arrangement allows for unwanted food (food that would otherwise be considered waste) to be utilized; it acts as a vent for unwanted food, allowing large corporate entities to dump surplus product of questionable nutritional quality upon the PEFS. Simultaneously, these corporations are receiving tax breaks and benefiting from policies that minimize their legal risk. Approximately 80 percent of food banks belong to Feeding America, a member organization that acts as an advocate and mediator in soliciting food from major food companies and bulk emergency food providers. This network has 205 food bank members that distribute food and grocery products to charitable organizations. Nationwide, more than 37 million people accessed Feeding America's private food assistance network in 2009 (up 46 percent from 2005), while 127,200 accessed it in New Hampshire (Feeding America, 2010b). Critiques of the PEFS Critical assessments of the PEFS range from those focused on political-economic relations to on-theground implementation of this redistributive system. In the following section we have grouped these appraisals into four main points. First, the PEFS is largely "emergency" in name only. Second, distribution of food in the PEFS is largely unregulated. Third, nutritional content of donated items is frequently overlooked for the sake of its quantity. Fourth, because of their limited budget and foodstorage capacity, the PEFS requests nonperishable, and resultantly, low-nutrition donations. Related to this point, perpetuation of the PEFS as it currently operates supports a short-term food strategy that supports immediate caloric need while sacrificing long-term health (and ignoring its associated costs). A prominent critique of the PEFS is that it is "emergency" in name only, and examples highlight the emergency programmatic emphasis of programs even though their services appear to be operating in a nonemergency manner. The U.S. government describes TEFAP as a program that "helps supplement the diets of low-income needy persons...by providing them with emergency food" (USDA FNS, 2010). Feeding America, "the nation's largest organization of emergency food providers," describes food pantries as "distributing food on a short-term or emergency basis" (the NHFB shares this definition) (Feeding America, 2010a, p. 13). According to Feeding America's Hunger in America 2010 report, approximately 79.2 percent of clients interviewed reported that they had used a pantry in the past year, indicating that they were not new clients. Multiple researchers have observed that many food pantries are being used on a regular, long-term basis (Beggs, 2006; Bhattarai, Duffy, & Raymond, 2005; Daponte, Lewis, Sanders, & Taylor, 1998; Hilton, 1993; Molnar, Duffy, Claxton, & Conner, 2001; Mosley & Tiehen, 2004; Tarasuk & Eakin, 2005; Warshawsky, 2010). Along these lines, others have cited how the PEFS is unregulated to its detriment; for instance, many private donations do not have any federal or state laws regulating their distribution (Bhattarai et al., 2005). The unregulated nature of any charity brings both benefits and burdens, and one benefit to the PEFS has been the ability to utilize the efforts of a large volunteer base. However, it has been proposed that pantries that operate with a largely volunteer workforce employ subjective eligibility criteria and a "they should be satisfied with whatever they get" mindset on behalf of workers (volunteers as well as paid staff) (Tarasuk & Eakin, 2005, p. 182). Food pantry clients may have limited rights and entitlement to the food being distributed, "further reinforcing that people are unable to provide for themselves" (Molnar et al., 2001, p. 189) in this redistributive system. In fact, it has been shown that workers "routinely eschew the aesthetic values that dominate our retail system" where "distribution of visibly substandard or otherwise undesirable products is achieved because clients have few if any rights" and "are in desperate need of food" (Tarasuk & Eakin, 2005, p. 184). The belief of some workers that clients should be satisfied with whatever items they receive underlies the non-nutritional focus threaded throughout the private emergency food system. This is especially evident from the supply side. Government commodities serve as a major source of food for the PEFS. Commodity foods are provided to food banks, directly to independent agencies, and to Feeding America (Feeding America, 2012c). The original intents of this commodity program were to distribute surplus agricultural commodities and reduce federal food inventories and storage costs, while simultaneously helping food-insecure populations. In 1988, however, much of the federal government's surplus had been exhausted, and as a result the Hunger Prevention Act of 1988 appropriated funds for the purchase of commodities for TEFAP (USDA FNS, 2010). The PEFS's other major contributor, private corporations, do not explicitly concentrate on the nutritional content of their donations. Corporations benefit from considerable tax incentives along with liability protection; they can donate food that would otherwise be wasted, forgoing dumping costs while engaging in what many of these entities now call "corporate social responsibility." For instance, pounds of donated food are showcased and used as progress markers to show how successfully hunger is being combated. Feeding America states that it distributes 3 billion pounds (1.4 billion kg) of food every year (Feeding America, 2012a). Clicking on a few of Feeding America's "Leadership Partners" on its homepage website (Feeding America, 2012b) yields similar language. For instance, ConAgra states that, "In the last dozen years, ConAgra Foods has provided more than 166 million pounds of food to families in need" (ConAgra, 2009, para. 5), Food Lion (part of the Delhaize Group) has "donated more than 21 million pounds of food" (Food Lion, 2010), and "just last year, Procter & Gamble contributed nearly 30 million pounds of product" (Procter & Gamble, 2010). These figures provide no indication of nutritional content, although one pound of naturally flavored drink boxes has different nutritional composition than one pound of fresh produce. If success is measured in terms of quantity, then this will be the criterion that drives emergency food provisioning. Charities are easy targets for critique; they often operate on a shoestring, use labor with different levels of knowledge and experience, and much of the time are put in a financially and socially powerless position, at the whims of donors. One result is that nonperishable or lowperishability items are preferred (Tiehen, 2002; Verpy, Smith, & Reicks, 2003); these last longer and do not require refrigeration. Their long shelf life means handling and transport is not timesensitive. These products cost less and are more likely to be donated. Nutrient-poor foods are less healthy overall (Monsivais & Drewnowski, 2007); previous food pantry investigations discovered the poor nutrient composition of donated items, especially in regards to adequate levels of calcium, vitamin A, and vitamin C (Akobundu, Cohen, Laus, Schulte, & Soussloff, 2004; Irwin, Ng, Rush, Nguyen & He, 2007). Donating large amounts is important since donation quantity is prioritized by agency recipients. Rock, McIntyre, and Rondeau (2009) found a misalignment between donor intent and client preference indicative of the "ignorance among food-secure people of what it is like to be food-insecure" (p. 167). Food banks and food pantries are pressured to accept foods on unfair grounds, just as clients are pressured to accept whatever food is handed to them. In at least one other case, food pantry donors "did not consciously consider nutrition when deciding which foods to donate" (Verpy et al., 2003, p.12). A demand-side perspective of private emergency food provisioning reveals somewhat complementary conditions that support the acquisition and distribution of low-quality foods. The longterm health consequences associated with the consumption of low-quality foods can be overlooked to satisfy immediate food needs, thereby reinforcing the value placed on the low-quality supply being donated. While expenses like shelter, heat, and medical expenses are relatively inelastic, food is flexible and can be adjusted based on these demands. On a limited budget, it is often the case that whatever money is leftover is used for food (Furst, Connors, & Bisogni, 1996; McEntee, 2010). As reported by McEntee, a homeless shelter resident commented: It's likes this, your oil's almost out, your electricity's high and they're going to shut it off, what are going to do? Well, we're going to have to cut down on our food budget. Do what you gotta do. . . you can buy your family packs and suck it up and eat ramen noodles. (McEntee, 2010, p. 795) Sometimes these types of food are chosen out of necessity (that is the only type of food offered) and other times it is out of habit (they are used to eating it).2 With the recent recession in the U.S. economy, purchases of cheap, ready-to-eat processed foods have increased. An Associated Press article entitled, "ConAgra Foods 3Q profit rises, maintains outlook" (Associated Press, 2010, para. 1) states: Strong sales of low-priced meals such as Banquet and Chef Boyardee and lower costs pushed ConAgra Foods Inc.'s third-quarter profit up 19 percent. Cheap prepared foods like those that ConAgra offers have appealed to customers during the recession as they look for ways to save money and eat at home more. Methods and Research Setting Approximately 7.7 percent of New Hampshire's population is food-insecure (Nord, Andrews & Carlson, 2008); 8 percent of the state's population lives in poverty, while 9.4 percent of Grafton County's population lives in poverty (U.S. Census Bureau, 2008). Grafton County was selected as the research site based on proximity to researchers as well as the existence of food insecurity. Grafton County (figure 2) has a population of 81,743 and a population density of 47.7 people per square mile (18.4 people per square kilometer) (U.S. Census Bureau, 2008). Unlike the other two primarily rural northern counties of New Hampshire (Carroll and Coos counties), Grafton County contains two universities that serve as educational and cultural centers (Dartmouth University in Hanover and Plymouth State University in Plymouth). Accordingly these areas attract residents with above-average educational attainment and income, thus offering a variegated set of social and economic conditions which are differentiated from the rest of the county. There are 14 registered food pantries in Grafton County (of a total of 165 in New Hampshire) (New Hampshire Food Bank, 2010). In 2012, there were 92 SNAP-authorized stores within the county, marking a 13 percent increase from 2008 (USDA FNS, 2012a). Approximately 16 percent of students were free lunch eligible in 2008 (USDA FNS, 2012b). In terms of local food potential, there were 10 farmers' markets in 2010 (USDA AMS, 2012) with 3.3 percent of farm sales attributable to direct to consumer sales ; U.S. Census of Agriculture, 2012). A purposive sampling method (Light, Singer, & Willett, 1990) was used to identify respondents (N = 16) who work regularly in Grafton County's PEFS. This included state employees, although the majority were workers and volunteers at food banks, soup kitchens, food pantries, and homeless shelters. These respondents were selected based on their above-average knowledge about hunger, food insecurity, and private emergency food provisioning in Grafton County (beyond their personal experience). Although some questions were specific to the respondent's area of expertise, the same general open-ended question template was used to facilitate informative discussion on topics related to food access, such as affordability, nutrition, and food provisioning (see table 1). The one-on-one semistructured interviews (Morgan & Krueger, 1998) with this group of respondents lasted between 60 and 90 minutes and took place in an office setting, community center, or over the phone (when in-person meetings were difficult to arrange). All interviews were recorded, transcribed, and coded. Participant observation (Flowerdew & Martin, 1997) was conducted at a Plymouth-area soup kitchen that served weekly hot meals for free to attendees. Data from interviews as well as field notes were coded and analyzed using NVivo, qualitative analysis software ( QSR International, 2010). After data was cleaned, data was examined as a whole to gain a general sense of overall meaning and depth. Open coding was undertaken, where material was organized into groups or segments of related information (Rossman & Rallis, 1998). We developed a qualitative codebook for efficient and consistent code assignment. Codes were examined, as well as the overall corpus of information. We identified underlying themes based primarily on respondent narratives. Over time, themes and trends emerged. Overlaps and differences between themes were identified, thus allowing their properties to be refined, ultimately resulting in progressively clear theme categories. Following theme assessment, interconnections and relations between themes were identified through concept mapping and triangulation (Fielding & Fielding, 1986). The authors conducted all interviews and observation, processed all data, and conducted all analysis. Institutional Review Board approval was obtained and all standard research protocols used. Findings from Grafton County Some of the data emerging out of the Grafton County case echoes previous observations about the PEFS. The preliminary data we present in this article is the product of field work, policy evaluation, and literature review. We do not claim that these findings are externally generalizable, although we do see similarities between our observations and those of other researchers, indicating that our data may be indicative of trends elsewhere, especially in rural areas of the northeastern United States where similar demographic and cultural traits exist. In this way, we also see potential in terms of research trajectories and policy reforms for those looking to build capacity between the PEFS and the local food system. Reliance upon Volunteers In relation to the existing criticisms that the PEFS is actually serving a long-term and sustained need and not a short-term or emergency one, many food pantry workers indicated that longterm usage by clients was common. For instance, one pantry worker explained that "most of the people that come in here are...I don't know if I would say chronic, but regulars" (0607).3 In these pantries, representatives talked about getting to know clients over the course of months and years of use; some clients stay and talk with pantry workers for emotional support during food pickups. This long-term usage has been critiqued and connected to the fact that the PEFS is so heavily reliant upon volunteer labor that resultantly there are opportunities for inconsistencies to develop (Lipsky, 1985; Molnar et al., 2001). Ad hoc administration of private emergency food distribution has consequences, such as inconsistent eligibility requirements and quality control (Daponte & Bade, 2006). In Grafton County pantries, eligibility was determined through a combination of criteria, such as pantry worker's personal judgment and preset income criteria. In one large pantry, more refined conditions were followed by staffand volunteers. In this pantry, if it was a client's first visit, then they were allowed to get food no matter what. However, in order to get food on subsequent visits they would need to bring proof of income (their income had to be below a certain amount based on number of household members). The director of this pantry explained, "the only time I turn them away is if they're using the other food pantries....Most of the time they trip themselves up" (0505). When asked about the consequences of using more than one pantry, the same respondent said, "I turn them offfor a whole year....To me, that's stealing food because that's government food involved in both places" (0505). This was not a set rule or policy of the pantry, but a guideline created by the director. Another worker explained that clients needed to fill out a TEFAP form (which determines eligibility under the rubrics of "Program" (already receiving a form of public assistance) and "Income" (one-person weekly income at or below USD370)), but that "it [the form] doesn't turn anybody away" (1215). The downside of a more subjective, informal system is that pantries can be run in a potentially inequitable manner (Daponte & Bade, 2006). In addition, a client who offended a staffmember or volunteer in the past will not be safeguarded against as they would be in a government-run system. A pantry director from a small church-run pantry was asked about assistance eligibility and replied that: We don't ask a lot of questions...We don't take any financial information and you don't need to qualify. I just tell people, "if you need it, you can use it."...You can tell by looking at them, you know? The car they drive, their clothes, you could tell they're not living high offthe hog, so to speak. (0607, emphasis added) In New Hampshire, 92 percent of food pantries and 100 percent of soup kitchens use volunteer labor, while 64 percent of pantries and 46 percent of soup kitchens rely completely on volunteer labor (Feeding America, 2010b). Volunteers partnered with pantry staffto perform tasks. Food has to be inspected, sorted, organized, and in some cases cleaned before it is handed out; how these tasks are carried out varies by pantry. In all pantries visited as part of this research, clients waited in line with other recipients (visible to each other) where nonpantry visitors to the agency could see them openly. In one venue, while pantry clients picked their food from a closet in a church, people working to set up a church dinner worked in the same room; these individuals and the pantry clients were visible openly to each other. These patterns show that by engaging in this private form of food assistance, clients give up any right to confidentiality they may be afforded through other forms of assistance, such as those offered by federal or state forms of food assistance. Another consequence of reliance on volunteer labor is that food standards are frequently disregarded. A set of pantry workers explained how they went to great lengths to utilize some squash donated from a nearby farm: We discovered a couple years ago that he can't keep it here [the pantry] because it will spoil...and then I said I'll take it, I got a place....So now I've got squashes and I keep an eye on them to make sure they aren't spoiling....So I have a room downstairs [in her house] that has no windows and it's about 55 [degrees]. And I put them down in the basement and then I bring them up into the garage and they're stored in the garage where it doesn't freeze. (0506) Pantry and food bank workers often clean and repackage food that is inconveniently packaged (e.g., in bulk) or has been broken open.4 These findings not only underscore the role of volunteer subjectivity, but they more broadly illustrate the negative externalities that can emerge in this unregulated system. Food Preferences: "Change Your Taste Buds" Depending on the agency, food preferences of clients may have minimal influence over foods received. Nutritional, cultural, or taste preferences can be disregarded, while pantry staffbeliefs dictate allotments. A volunteer who worked at a pantry and soup kitchen and also served on the board of the pantry said, "the younger ones [clients] are very, very fussy, they are turning their nose up at different things....Whereas if you're hungry, you accept and you learn to do it and change your taste buds" (0506, emphasis added). In the same interview as the one quoted above, this respondent reflected that "we're a spoiled society" and "there's a lot of honest need, but I think there's also those that are needy who don't help themselves" (0506). This respondent seems to believe that clients should be thankful for whatever they get, no matter what, since it is better than nothing. This is similar in a sense to how pantries are pressured into being thankful for all donations out of fear that refusal of items would jeopardize future giving (for an example, see Winne (2005)). Believing that clients should "change their taste buds" to accommodate the food available at the pantry food represents a misalignment between clients' nutritional well-being and the pantry objective of efficiently distributing all donated food. This respondent held a position of power within the pantry and was able to make managerial-level decisions. Following through on her sentiments means that clients should adjust their personal taste preferences to whatever donors decide to donate. Client preferences are interpreted by pantry staffin number of ways; consider the experience of this employee who worked at a smaller pantry in a northern part of the county: I had a guy call me today and wanted me to take his name offthe list here and I said "OK." I said "did you get a job?" I know he was looking for a job, "no, but I can't eat that crap." He said, "I like to eat organic now, natural food." He said, "I can't eat this stuff, processed kind of food." He said, "not that I don't appreciate what you're doing for me, but I just can't eat that kind of food." I said, "well, get a job" or that's what I felt like saying....Do you know how much that stuffcosts? We're not the end all, we're just supplemental here, we can't provide food for you for the week. I mean its just not going to happen. (0607) This employee appeared offended by this man's decision to stop accessing the pantry. By participating in the PEFS, these individuals relinquish rights and standards they may have in the public retail sphere (i.e., where federally and state enforced food safety regulations are upheld) and as a result are forced to gamble on the whims of the largely unregulated PEFS . This removal of food rights places food-insecure individuals in an even more food-precarious state, disempowering them beyond that which is accomplished through retail markets. One pantry worker explained that when individuals donate food, "lots of times it's ramen noodles because you can donate a lot at a low price" (0709). Food-pantry representatives working with a food-insecure population indicated that this group prefers quick and easy meals in the form of processed products, and also lacks adequate knowledge about nutrition and cooking to make informed food selections. Simultaneously, those accessing pantries revealed that food was a flexible budget item that could be adjusted according to the demands of other expenses. This often leads to trading down of items purchased - from more expensive, healthy items to cheaper, less healthy items. Food pantry representatives commented on how clients, especially young ones, prefer quick and easy products because "it's so much easier to open a can...things that are quick" (0506). Another pantry worker commented that "it's great when they say they cook....It just makes it so much easier to give them bags of nutritional food, but sometimes they'll just want the canned spaghetti, macaroni and cheese, hot dogs...foods that are easy to prepare for families," which she acknowledged as "a problem" (0709). Efforts to reform these eating habits were evident; one pantry worker reflected on how they had tried to switch from white to wheat bread, but found that "the wheat bread was not a hit" (1215). A nutrition professional working at a nonprofit described an attempt to change her clients' eating habits. She explained that her efforts were aimed at making people more nutritionally informed by showing them that eating healthier can be more affordable: We will do a comparison and we will make a meal with Hamburger Helper and we'll make basically homemade Hamburger Helper....I'll do a comparison of what Hamburger Helper costs and what it costs to make it from scratch. It's always of course cheaper to make it from scratch and then we do a taste test. And unfortunately many of the people have grown up with Hamburger Helper so that's what they like....They don't see the difference; how salty and awful it tastes....We'll do a whole cost analysis and they'll see it's about 59 cents a serving if you make it from scratch compared to about 79 cents a serving for Hamburger Helper. (1013) Another pantry worker explained: I think it's pricing, but then we have people, you know I believe it comes from how you grew up. You know, a lot of people shop the way their moms or dads shopped. And some people were just brought up on frozen boxed food and not cooked homemade meals and so that's all they know how to purchase. (0303) This may explain why pantries experience a demand for these easy-to-cook processed foods. While some pantries might push more nutritional options, others send contradictory nutritional messages. Not far from where the abovementioned nutritional professional worked, another pantry worker at the same agency remarked that "the stuffthat's easy for us to get is pasta, canned stuff, pasta mixes, and it's not highly nutritional....Tuna or some kind of a tinned meat, you know, with a Tuna Helper, that's the kind of stuffwe get here because we don't have any way to give them fresh meat" (0607). The food being donated is free for the pantry and free for the clients, made possible through private, often corporate donors. This represents a seemingly collaborative alignment between the need to dispose of unwanted food on behalf of corporate donors and the need for foodinsecure clients to consume food, yet this arrangement is rooted in a short-term outlook and power imbalance where corporate food entities are able to dump unwanted food for free upon a foodinsecure population, thereby realizing short-term profit gains (for the business) at the cost of longterm health of food-insecure individuals and its effect on governments. Assessing Collaborative Potential The rural PEFS appears to be similar to the urban PEFS in a number of ways. It is heavily reliant upon volunteer labor and it serves a significant proportion of the population, often on a regular basis. In the rural context there is a dispersed population. While centralized population centers like cities provide efficient and short-distance transportation networks, rural networks are decentralized with people living in remote areas, often requiring automobile access. This has a few practical consequences. A dispersed population also means that community food-growing opportunities like neighborhood gardens are more difficult to organize and implement when compared to a city where a group of neighbors can have a small vegetable plot within walking distance. Contrastingly, in many rural places the transportation cost of getting to a community space where a garden may be located represents another financial and logistical barrier. Cities are also places where people can more easily congregate to meet and organize reactive and proactive responses to inadequate food access (for example, to grow a neighborhood garden in response to being located in a "food desert"). In urban areas for instance, these have manifested in food justice efforts. In rural areas, the PEFS is the chief response to hunger and food insecurity (in addition to federal and state mandated programs). However, the rural PEFS operates on a smaller scale with fewer numbers of people accessing it and a high degree of malleability. As described earlier in this essay, this informality has been criticized; however, this ability to adapt means that individuals who operate PEFS entities (like food pantries) can take advantage of opportunities without having to obtain approval from higher levels of bureaucracy. In addition, the rural PEFS is often located where the land, soil, water, and air resource base for growing food is abundant. In contrast to the literature that supports the claims that low-income populations prefer processed foods (Drewnowski & Specter, 2004), data from the Grafton County case shows that in the pantries that were able to obtain small amounts of fresh, perishable foods (meats and fresh fruits and vegetables), these quickly became the most popular items. As one pantry worker explained: Most people know that an apple is healthier than a hot dog, but those [hot dogs] are way cheaper, you know, not that they're the same in any way....Here [at the food pantry] they would go for the things that they don't normally get their hands on, which is why those dairy products go fast and those veggies go fast. But I think in general when they are shopping they go for the cheapest, easiest thing to get through to the next week. (1215) In another study of Grafton County, a food pantry employee described how a local hunter donated moose meat: Interviewer: What are the most popular items that you have here in the pantry? Respondent 1: Meat. It's the most expensive... Respondent 2: Oh, was it last year we got the moose meat? We got 500 pounds [230 kg]. And we're thinking, what are we gonna do with all this moose meat? And it flew out of here. I mean, people were calling us and asking us for some. (McEntee, 2011b, p. 251) A key question emerging from this research is, "how do we harness the assets of both the PEFS and local food system to better serve the needs of food-insecure populations?" There is a demand for locally produced produce and meat on behalf of food-insecure individuals (as others have shown; see Hinrichs and Kremer (2002)). The desires of low-income consumers to eat fresh meat and produce (which often is locally produced) as well as to participate in some local food production activities (whether it be hunting or growing vegetables) have been overlooked by researchers. People accessing the PEFS in rural areas are accessing pantries, but also growing their food because it is an affordable way to obtain high-quality food they may otherwise not be able to afford (McEntee, 2011b). Based on the information provided in this article, potential synergies between the PEFS and the local food system in the rural context exist. Specifically, a traditional localism engages "participants through non-capitalist, decommodified means that are affordable and accessible" where "food is grown/raised/hunted, not with the intention to gain profit, but to obtain fresh and affordable food" (McEntee, 2011, pp. 254-255). Traditional localism allows for local food to become an asset for many food-insecure and poor communities that are focusing on the need to address inadequate food access. How could the rural PEFS source more food locally, thereby strengthening the local economy? How could private emergency food entities like food pantries and local food advocates promote food-growing, food-raising, and hunting activities as a means to increase grassroots, local, and affordable access to food? Like many places throughout the U.S., Grafton County is home to small-scale local agriculture operations supported by an enthusiastic public and sympathetic state. Simultaneously, there is the presence of food insecurity and a PEFS seeking to remediate this persistent problem. The actual structure of the PEFS could be thoroughly assessed (beyond the borders of Grafton County). If warranted, this system could be redesigned to prioritize privacy and formalize procedures in terms of ensuring that client food choices are respected. A crucial next step in reforming this system to benefit lowincome and minority clients is to emphasize the ability to grow, raise, and hunt food for their own needs5 through the traditional local concept. This would represent a transformation in which these activities could not only be supported by the PEFS, but also draw upon the social capital of communities in the form of memories and practices of rural people from the near past, all while reducing reliance upon corporate waste. If traditional local efforts were organized on a cooperative model, based on community need and not only the needs of individuals, it would benefit all those participating, drawing on collective community resources, such as food-growing knowledges and skills, access to land, and tools, thereby enhancing the range of rural livelihood strategies. In this sense, these activities are receptive to racial and economic diversity as well as alliance-formation across social groups and movements, all of which are characteristic of the food sovereignty movement (Holt- Giménez & Wang, 2011). In moving forward additional research is needed. While our findings highlight potential shortcomings, there is a lack of data exploring the rural PEFS experience. Specifically, from the demand side, we need more data about the users of this system, specifically in regard to their satisfaction with food being given to them. Are they happy with it? Do they want something different that is not available? Do they lack the ability to cook certain foods being handed out by the pantry? Feeding America's Hunger in America survey asks about client satisfaction; in its 2010 report, only 62.7 percent of surveyed clients were "very satisfied" with the overall quality of the food provided.6 Additionally, the fact that this survey is administered by the same personnel who are distributing food donations raises methodological biases. More needs to be discovered about why such a large proportion of users is not "very satisfied." From the supply side, we need to know more about food being distributed and its nutritional value. Currently, the food being donated and distributed is unregulated to a large degree, especially in rural pantries. Also on the supply side, the source of food provided to Feeding America as well as individual state food banks and food pantries needs to be inventoried with more information beyond just its weight. Knowing the quantity of specific donated products as well as the financial benefit (in terms of tax write-offs) afforded to donors would add transparency. Conclusion: Neoliberal Considerations and Future Directions The findings we have presented in this article are intended to reveal important policy questions about the PEFS and local food movement; we do acknowledge, however, that it also has raised some important questions. In summary, we see opportunities to move forward in enacting a food sovereignty agenda with both local and global scales in mind. First, value-added, market-based local solutions used to address the inadequacies of the current food system are immediately beneficial. However, these should not be accepted as the endall solution. Looking beyond them to determine what else can be accomplished to change the structure of the food system to shiftpower away from oligarchic food structures of the corporate food regime to food citizens, not only food consumers, would result in systemic change. A key consideration in realizing any reform in the PEFS, and simultaneously challenging and transforming the unsustainable global food regime, is recognizing the neoliberal paradigm in which government and economic structures exist. Neoliberalism can be defined as a political philosophy that promotes market-based rather than state-based solutions to social problems, while masking social problems as personal deficiencies. The PEFS is essentially acting as a vent for unwanted food in this system that also provides a financial benefit to the governing food entities (i.e., food businesses). Too often alternatives are hailed as opposing the profit-driven industrial food system simply because they are geographically localized; in reality, they may re-create the classist and racist structures that permeate the larger global system.7 The PEFS is an embedded neoliberal response to food insecurity; while public-assistance enrollment is on the rise, so is participation in the PEFS. This is a shiftin responsibility in who is providing assistance to food-insecure populations from the government to the private sector. In this sense it is a market-based approach to addressing food insecurity (i.e., by dumping food on the private charity sector, market retailers cut their own waste disposal costs), and the result is continual scarcity and the establishment of a system that reinforces the idea that healthy food is a privilege, only accessible to those with adequate financial and social capital. Along these same lines, a form of food localism exists that is arguably detrimental to those without financial and social capital; these efforts have and continue to frame food access solely as an issue of personal responsibility related to economic status and nutritional knowledge (a narrative thoroughly discussed by Guthman (2007, 2008)). This prioritizes market-based solutions to developing local food systems as well as universal forms of food education that emphasize individual health. As Alkon and Mares (2012) explain, Neoliberalism creates subjectivities privileging not only the primacy of the market, but individual responsibility for our own wellbeing. Within U.S. food movements, this refers to an emphasis on citizen empowerment, which, while of course beneficial in many ways, reinforces the notion that individuals and community groups are responsible for addressing problems that were not of their own making. Many U.S. community food security and food justice organizations focus on developing support for local food entrepreneurs, positing such enterprises as key to the creation of a more sustainable and just food system. The belief that the market can address social problems is a key aspect of neoliberal subjectivities. (p. 349) Though elements of both the PEFS and the local food system have arguably been folded into neoliberalization processes through market-based mechanisms, incremental steps to change these dynamics are possible. Reframing issues of food accessibility (including food insecurity, hunger, food deserts, etc.) as issues of food justice moves us beyond an absolute spatial understanding of food issues. For instance, when we only look at physical access to food, we often disregard the more important considerations of class, race, gender (see Alkon and Agyeman, 2011), and sexual orientation that define a person's present position (and over which they often have no control) and which dictate how they engage with the food system. These considerations are present in current food-justice efforts, which seek to ensure that communities have control over the food grown, sold, and consumed there. Rural food justice has been defined using the traditional localism concept: Traditional localism in rural areas engages participants through non-capitalist, decommodified means that are affordable and accessible. Food is grown/raised/hunted, not with the intention to gain profit, but to obtain fresh and affordable food. A traditional localism disengages from the profit-driven food system and illustrates grassroots food production where people have direct control over the quality of the food they consume - a principal goal of food justice. (McEntee, 2011b, pp. 254-255) Utilizing this rural form of food justice involves more than promoting individual food acquiring techniques; it involves developing organizational and institutional strategies that improve the quality of food available to PEFS entities. This is currently accomplished by some, such as when pantries obtain fresh produce through farmer donations or when a food bank develops food-growing capacity. 8 But these types of entities are in the minority. The next stage of realizing food justice, we posit, is to determine how a food sovereignty approach can be utilized in a global North context. Food justice predominantly operates to find solutions within a capitalist framework (and it has been criticized as such) while food sovereignty is explicitly geared toward the dismantling of this system in order to achieve food justice. Regime change and transformation requires more than recognition and control over food-growing resources; it requires alliance and partnership-building between groups to "to address ownership and redistribution over the means of production and reproduction" (Holt- Giménez & Wang, 2011, p.98). Adopted by organizations predominantly located in the global South, food sovereignty is focused on the causes of food system failures and subsequently looks toward "local and international engagement that proposes dismantling the monopoly power of corporations in the food system and redistributing land and the rights to water, seed, and food producing sources" (Holt-Giménez, 2011, p. 324). There is an opportunity for people in the global North not only to learn from the global South food sovereignty movements, but to form connections and alliances between North and South iterations of these movements.9 As discussed above, the dominant food movement narrative is in sync with the economic and development goals of government (e.g., state-sanctioned buy-local campaigns) as well as marketing prerogatives of global food corporations (e.g., "local" being used as marketing label). Building a social movement powerful enough to place meaningful political pressure upon government to support a food system that prioritizes human wellbeing, not profit, is an immediate challenge. Incremental solutions are necessary in order to improve the lives of people now. However, these local solutions, such as innovative farm-to-school programming and other viable models between the local food environment and the PEFS that we have discussed in this article, would be more effective at affecting long-term systemic change if they were coupled with collective approaches to acknowledge and limit the power of the corporate food regime to prevent injustice, while also holding the state accountable for its responsibility to citizens, which it has successfully "relegated to voluntary and/or market-based mechanisms" (Alkon and Mares, 2012, p. 348). Food sovereignty offers more than an oppositional view of neoliberalism, however. The food sovereignty movement advances a model of food citizenship that asserts food as a nutritional and cultural right and the importance of democratic on-the-ground control over one's food. These qualities resonate with food-insecure and disenfranchised communities, urban and rural, in both the global North and South. Sidebar Citation: McEntee, J. C., & Naumova, E. N. (2012). Building capacity between the private emergency food system and the local food movement: Working toward food justice and sovereignty in the global North. Journal of Agriculture, Food Systems, and Community Development, 3(1), 235-253. http://dx.doi.org/10.5304/jafscd.2012.031.012 Copyright © 2012 by New Leaf Associates, Inc. Footnote 1 Cartesian understandings of space utilize a grid-based measurement of physical proximity. These types of proximitybased understandings of food access (i.e., food access is primarily a matter of bringing people physically closer to food retailers, as is promoted by the USDA Food Desert Locator) tend to overlook other nuanced forms of food access based on knowledge, culture, race, and class. 2 The amount of processed food, especially in the form of prepared meals and meals eaten outside the home, is steadily increasing in the United States (Stewart, Blisard, & Jolliffe, 2006). 3 The four-digit number indicates interview location and respondent IDs. 4 A leading antihunger effort in New Hampshire is the New Hampshire Food Bank (NHFB), the state's only food bank and a member of Feeding America. In 2008 the NHFB "distributed over 5 million pounds of donated, surplus food to 386 food pantries, soup kitchens, shelters, day care centers and senior citizen homes" (N.H. Food Bank, 2010). In total N.H. has 441 agencies registered with NHFB that provide food to 71,417 people annually. Grafton County has 18 food pantries, which "distribute non-prepared foods and other grocery products to needy clients, who then prepare and use these items where they live" and where "[F]ood is distributed on a short-term or emergency basis until clients are able to meet their food needs" (N.H. Food Bank, 2010). 5 A noteworthy example of an organization that has begun to accomplish these objectives is The Stop Community Food Centre in Toronto, which was recently described by Levkoe and Wakefield (2012). 6 The remaining categories are: "Somewhat satisfied" (31.3 percent), "Somewhat dissatisfied" (4.8 percent), and "Very dissatisfied" (1.3 percent). 7 For additional discussion of the political economic transition from government to governance, such as the transfer of state functions to nonstate and quasistate entities, see Purcell (2002). 8 An example of this type of effort is that of the Vermont Food Bank, which purchased a farm in 2008 in order to supply the food bank with fresh, high-quality produce as well as to sell the produce. 9 The U.S. Food Sovereignty Alliance has recognized the importance of building these coalitions: "As a US-based alliance of food justice, anti-hunger, labor, environmental, faith-based, and food producer groups, we uphold the right to food as a basic human right and work to connect our local and national struggles to the international movement for food sovereignty" (US Food Sovereignty Alliance, n.d., para. 1). 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Naumova b Department of Civil and Environmental Engineering, Tufts University, and Tufts Initiative for the Forecasting and Modeling of Infectious Diseases Submitted 2 May 2012 / Revised 28 June and 26 July 2012 / Accepted 27 July 2012 / Published online 4 December 2012 aCorresponding author: Jesse C. McEntee, PhD, Managing Partner, Food Systems Research Institute LLC; P.O. Box 1141; Shelburne, Vermont 05482 USA; +1-802-448-2403; www.foodsystemsresearchinstitute.com; jmcentee@foodsri.com b Elena N. Naumova, PhD, Associate Dean for Research, School of Engineering; Professor, Department of Civil and Environmental Engineering, Tufts University; also Tufts Initiative for the Forecasting and Modeling of Infectious Diseases (InForMID) (http://informid.tufts.edu/); elena.naumova@tufts.edu Acknowledgments: The authors are grateful to the Economic and Social Research Council's Centre for Business Relationships, Accountability, Sustainability and Society at CardiffUniversity as well as the Center for Rural Partnerships at Plymouth State University for financial support during this research. The authors are also grateful to the three anonymous reviewers who provided constructive feedback on earlier drafts of this article. Word count: 11055Show lessYou have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. 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More like this Building capacity between the private emergency food system and the local food movement: Working toward food justice and sovereignty in the global NorthMcEntee, Jesse C; Naumova, Elena N. Journal of Agriculture, Food Systems, and Community Development; Ithaca Vol. 3, Iss. 1, (Fall 2012): 235-253. 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[[missing key: loadingAnimation]]The full text may take 40-60 seconds to translate; larger documents may take longer.Cancel OverlayEndTurn on search term navigationTurn on search term navigationJump to first hitListen Headnote Abstract One area of food system research that remains overlooked in terms of making urban-rural distinctions explicit is the private emergency food system of food banks, food pantries, soup kitchens, and emergency shelters that exists throughout the United States. This system is an important one for millions of food-insecure individuals and today serves nearly as many individuals as public food assistance. In this article, we present an exploratory case that presents findings from research looking at the private emergency food system of a rural county in northern New England, U.S. Specifically, we examine the history of this national network to contextualize our findings and then discuss possibilities for collaboration between this private system and the local food movement (on behalf of both the public and the state). These collaborations present an opportunity in the short term to improve access to high quality local foods for insecure populations, and in the long term to challenge the systemic income and race-based inequalities that increasingly define the modern food system and are the result of prioritizing market-based reforms that re-create inequality at the local and regional levels. We propose alternatives to these approaches that emphasize the ability to ensure adequate food access for vulnerable populations, as well as the right to define, structure, and control how food is produced beyond food consumerism (i.e., voting with our dollars), but through efforts increasingly aligned with a food sovereignty agenda. Keywords emergency food, food justice, food sovereignty, rural and urban Introduction The rural private emergency food system is an overlooked area of research. The popularity of local food has increased in urban and rural areas alike, yet despite the social and economic capital driving this innovative food movement, foodinsecure populations remain ignored to a large degree. We know that the rural food environment is substantively different than the urban food environment (Sharkey, 2009). People in rural areas generally have less money to spend on food and they live further from markets where local food producers sell their products (Morton & Blanchard, 2007). Producers are predominantly located in rural areas where land and water resources are abundant, yet the most profitable markets for their products more often than not are located in urban centers where they can more easily access a concentrated population center with greater financial capital. These urban-rural distinctions can be made about multiple aspects of food systems research. For instance, early applications of the food desert concept (and the corresponding efforts to identify them) were overwhelmingly situated in urban places. Today, there is recognition that there is not a single food desert definition that can be universally applied. Researchers as well as government authorities have recognized this; for instance, the United States Department of Agriculture (USDA) has adopted different criteria for urban and rural food deserts. In examinations of local food, some have identified key urban-rural distinctions. For example, McEntee's (2010) contemporary and traditional conceptualization has been used to distinguish between a broad base of activities that are local in terms of geographical scale, but potentially exclusive in terms of their social identity and obstacles to adequate access. Access in this sense is not represented by a Cartesian notion of physical proximity, however; it is also indicative of access barriers in terms of financial ability as well as structural and historical (e.g., institutional racism) processes that privilege some, but harm others (McEntee 2011a).1 These concerns are increasingly recognized as part of growing food justice and food sovereignty agendas. The private emergency food system (PEFS) is a national network of food banks, food pantries, soup kitchens, and shelters that operate largely to redistribute food donated by individuals, businesses, and the state. This is a tremendously important system that serves both urban and rural food-insecure populations. Based on a review of this system's functionality, urban-based critiques of this system, and findings from an exploratory qualitative study, we propose that there are key distinctions between the urban and rural PEFSs that have been overlooked (in the same manner that urban and rural local food systems are conflated). The PEFS serves as a safety net for many, yet it struggles financially and lacks access to the high-quality foods (e.g., fresh produce and meat) that clients of this system often prefer. In this article we present emergent opportunities to develop the collaborative capacity between the PEFS and the rural local food system in ways that address the needs of the PEFS and utilize the assets of the burgeoning local food movement. Furthermore, we explain how these synergies potentially contribute to food justice by providing high-quality food to low-income populations. We begin the article with a review of pertinent literatures. This is followed by a depiction of the PEFS, summary of existent critiques, and presentation of our data. We propose that livelihood strategies related to traditional localism (McEntee, 2010) contribute to food justice and food sovereignty agendas by focusing on the natural and social assets of rural communities. We conclude with a discussion of the possibilities for not only remediating the PEFS, but challenging the corporate food regime that currently institutionalizes it. Local Foods, Food Justice, and Food Sovereignty Consumer confidence in the conventional food sector has decreased as a result of food scares (Morgan, Marsden, & Murdoch, 2006), with consumers feeling alienated from modern-day food production (Sims, 2009). From these consumerbased concerns over food safety and a general alienation from modern-day food production, alternative food initiatives and movements have surfaced (including local food initiatives). Feenstra (1997) made the case for local foods as an economically viable alternative to the global industrial system by providing specific steps to be taken by citizens to facilitate the transition between the local and the global; it is these forces that have become the focus of food provisioning studies (Winter, 2003). These efforts include more sustainable farming methods, fair trade, and food and farming education, among others; these have been reviewed extensively elsewhere, such as by Kloppenburg, Lezberg, De Master, Stevenson, and Hendrickson (2000) and Allen, FitzSimmons, Goodman, and Warner (2003). Essentially, all are categorized by a desire to create socially just, economically viable, and environmentally sustainable food systems (Allen et al., 2003) and the majority are now collectively referred to as the dominant food movement narrative (Alkon & Agyeman, 2011). It is from this narrative that the local food movement emerges. Food justice efforts have successfully utilized food localization efforts to improve food access opportunities for low-income and minority communities. These efforts typically occur in urban areas and target low-income minority populations (Alkon & Norgaard, 2009; Gottlieb and Joshi 2010; Wekerle, 2004; Welsh & MacRae, 1998). The concept of food justice supports the notion that people should not be viewed as consumers, but as citizens (Levkoe, 2006); by linking low-income and minority populations with alternative modes of food production and consumption, advocates prioritize human well-being above profit and alongside democratic and social justice values (Welsh & MacRae, 1998). This represents "more than a name change" departure from conventional food security concerns; it is rather a systemic transformation that alters people's involvement in food production and consumption (Wekerle, 2004, p. 379). Increasingly substantiated by racial and income-based exclusion, food justice operates to prioritize just production, distribution, and access to food within the communities being impacted. This is the focus of the food justice movement, though environmental and economic benefits often result from these efforts as well. A recently published volume edited by Alkon and Agyeman (2011) unpacks various forms of food justice, ranging from issues of production (e.g., farmworker rights) to distribution, consumption, and access. In this article we are concerned with the consumption element of the food chain; food justice efforts in this realm often take the form of alternative food initiatives that create new market-based or charity-based solutions to inadequate food access (e.g., farm-to-school programming that link schools and local farmers, slidingscale payment plans for low-income consumers at farmers' markets that are subsidized by wealthier patrons, or agricultural gleaning programs) that stress social equity and solutions that are implemented by and for the people impacted by inadequate access to food. This latter element is a definitive characteristic of food justice initiatives. Most recently, Alkon and Mares (2012) situated food justice in relation to food sovereignty, finding that although food justice and community food security frameworks often challenge conventional agricultural and food marketing systems, the food sovereignty framework is the only one to explicitly underscore "direct opposition to the corporate food regime" (p. 348). This is because both contemporary food justice and (community) food security frameworks often operate within traditional markets that are agents of the industrial agricultural system representative of a neoliberal political economy. This marks a departure between food justice and food sovereignty; La Via Campesina, a major proponent of food sovereignty, defines the concept as: the right of peoples to healthy and culturally appropriate food produced through sustainable methods and their right to define their own food and agriculture systems. It develops a model of small scale sustainable production benefiting communities and their environment. It puts the aspirations, needs and livelihoods of those who produce, distribute and consume food at the heart of food systems and policies rather than the demands of markets and corporations. (La Via Campesina, 2011, para. 2) Whereas food justice often works to create solutions in sync with market structures by filling the gaps in government services, food sovereignty focuses on dismantling the corporate food regime. History and Structure of the PEFS An area of the food system where food justice advocates have increasingly engaged in an urban setting is the PEFS. Operating on a charity basis, emergency food assistance provides food to individuals whose earnings, assets, and social insurance options have not met their needs (Wu & Eamon, 2007). Public government-run assistance programs include welfare, the Supplemental Nutrition Assistance Program (SNAP), Medicaid, and subsidized housing. Private emergency food assistance is provided by nonprofit organizations and includes soup kitchens, food pantries, food banks, food rescue operations (Poppendieck, 1998), and "emergency shelters serving short-term residents" (emphasis added) (Feeding America, 2010a, p. 1). Largely in reaction to dissatisfaction with the federal food stamp program, Congress passed the Omnibus Budget Reconciliation Act in 1982. This act allowed federally owned surplus commodity food to be distributed by the government for free to needy populations. Prior to its passage, the vast majority of food assistance in the U.S. was governmentally provided through the food stamp program (now the Supplemental Nutrition Assistance Program [SNAP]) and the majority of food that food pantries received came from individuals and businesses. The act's success was followed by the Temporary Emergency Food Assistance Act (TEFAP) in 1983, which began the process of routinely distributing excess commodities through private emergency food programs, such as food banks and food pantries (Daponte & Bade, 2006). Food pantries flourished as a result of commoditysourcing, since they now began receiving a reliable stream of food. Businesses that previously did not want to be involved in emergency food provisioning activities could now dispose of unwanted inventory for a much cheaper rate by giving it away (Daponte & Bade, 2006) (see figure 1). In fiscal year 2009, Congress appropriated USD299.5 million for the program, made up of USD250 million for food purchases and USD49.5 million for administrative support (USDA FNS, 2010). In the U.S., companies defined as C corporations by tax code (the majority of U.S. companies) can collect an enhanced tax deduction for donating surplus property, including food. Thus when food businesses donate food to a charity, including food banks and pantries, the businesses can take a deduction equal to 50 percent of the donated food's appreciated value. In addition, the Bill Emerson Good Samaritan Food Donation Act of 1996 provides safeguards for entities donating food and groceries to charitable organizations by minimizing the risk of legal action against donors. Companies are not required to publicly disclose deductions for food donations, though in 2001 corporations wrote offUSD10.7 billion in deductions (Alexander, 2003). Feeding America received USD663,603,071 in charitable donations in 2006. In a 2003 Chicago Tribune article, Delroy Alexander described how America's Second Harvest received USD450 million in donated provisions in 2001, USD210 million of which came from just 10 major food companies, such as Kraft, Coca-Cola, General Mills, ConAgra Foods, Pfizer, and Tropicana (Alexander, 2003). The top five donors each gave more than USD20 million in food, with the top contributor at USD38 million. Current figures are unavailable, though many companies proudly display pounds of food donated on their websites. For instance, Walmart's website states: From November 2008 to November 2009, the Walmart stores and Sam's Club locations have already donated more than 90 million pounds [41,000,000 kg] of food....By giving nutritious produce, meat, and other groceries, we've become Feeding America's largest food donor. (Walmart, 2010) This arrangement allows for unwanted food (food that would otherwise be considered waste) to be utilized; it acts as a vent for unwanted food, allowing large corporate entities to dump surplus product of questionable nutritional quality upon the PEFS. Simultaneously, these corporations are receiving tax breaks and benefiting from policies that minimize their legal risk. Approximately 80 percent of food banks belong to Feeding America, a member organization that acts as an advocate and mediator in soliciting food from major food companies and bulk emergency food providers. This network has 205 food bank members that distribute food and grocery products to charitable organizations. Nationwide, more than 37 million people accessed Feeding America's private food assistance network in 2009 (up 46 percent from 2005), while 127,200 accessed it in New Hampshire (Feeding America, 2010b). Critiques of the PEFS Critical assessments of the PEFS range from those focused on political-economic relations to on-theground implementation of this redistributive system. In the following section we have grouped these appraisals into four main points. First, the PEFS is largely "emergency" in name only. Second, distribution of food in the PEFS is largely unregulated. Third, nutritional content of donated items is frequently overlooked for the sake of its quantity. Fourth, because of their limited budget and foodstorage capacity, the PEFS requests nonperishable, and resultantly, low-nutrition donations. Related to this point, perpetuation of the PEFS as it currently operates supports a short-term food strategy that supports immediate caloric need while sacrificing long-term health (and ignoring its associated costs). A prominent critique of the PEFS is that it is "emergency" in name only, and examples highlight the emergency programmatic emphasis of programs even though their services appear to be operating in a nonemergency manner. The U.S. government describes TEFAP as a program that "helps supplement the diets of low-income needy persons...by providing them with emergency food" (USDA FNS, 2010). Feeding America, "the nation's largest organization of emergency food providers," describes food pantries as "distributing food on a short-term or emergency basis" (the NHFB shares this definition) (Feeding America, 2010a, p. 13). According to Feeding America's Hunger in America 2010 report, approximately 79.2 percent of clients interviewed reported that they had used a pantry in the past year, indicating that they were not new clients. Multiple researchers have observed that many food pantries are being used on a regular, long-term basis (Beggs, 2006; Bhattarai, Duffy, & Raymond, 2005; Daponte, Lewis, Sanders, & Taylor, 1998; Hilton, 1993; Molnar, Duffy, Claxton, & Conner, 2001; Mosley & Tiehen, 2004; Tarasuk & Eakin, 2005; Warshawsky, 2010). Along these lines, others have cited how the PEFS is unregulated to its detriment; for instance, many private donations do not have any federal or state laws regulating their distribution (Bhattarai et al., 2005). The unregulated nature of any charity brings both benefits and burdens, and one benefit to the PEFS has been the ability to utilize the efforts of a large volunteer base. However, it has been proposed that pantries that operate with a largely volunteer workforce employ subjective eligibility criteria and a "they should be satisfied with whatever they get" mindset on behalf of workers (volunteers as well as paid staff) (Tarasuk & Eakin, 2005, p. 182). Food pantry clients may have limited rights and entitlement to the food being distributed, "further reinforcing that people are unable to provide for themselves" (Molnar et al., 2001, p. 189) in this redistributive system. In fact, it has been shown that workers "routinely eschew the aesthetic values that dominate our retail system" where "distribution of visibly substandard or otherwise undesirable products is achieved because clients have few if any rights" and "are in desperate need of food" (Tarasuk & Eakin, 2005, p. 184). The belief of some workers that clients should be satisfied with whatever items they receive underlies the non-nutritional focus threaded throughout the private emergency food system. This is especially evident from the supply side. Government commodities serve as a major source of food for the PEFS. Commodity foods are provided to food banks, directly to independent agencies, and to Feeding America (Feeding America, 2012c). The original intents of this commodity program were to distribute surplus agricultural commodities and reduce federal food inventories and storage costs, while simultaneously helping food-insecure populations. In 1988, however, much of the federal government's surplus had been exhausted, and as a result the Hunger Prevention Act of 1988 appropriated funds for the purchase of commodities for TEFAP (USDA FNS, 2010). The PEFS's other major contributor, private corporations, do not explicitly concentrate on the nutritional content of their donations. Corporations benefit from considerable tax incentives along with liability protection; they can donate food that would otherwise be wasted, forgoing dumping costs while engaging in what many of these entities now call "corporate social responsibility." For instance, pounds of donated food are showcased and used as progress markers to show how successfully hunger is being combated. Feeding America states that it distributes 3 billion pounds (1.4 billion kg) of food every year (Feeding America, 2012a). Clicking on a few of Feeding America's "Leadership Partners" on its homepage website (Feeding America, 2012b) yields similar language. For instance, ConAgra states that, "In the last dozen years, ConAgra Foods has provided more than 166 million pounds of food to families in need" (ConAgra, 2009, para. 5), Food Lion (part of the Delhaize Group) has "donated more than 21 million pounds of food" (Food Lion, 2010), and "just last year, Procter & Gamble contributed nearly 30 million pounds of product" (Procter & Gamble, 2010). These figures provide no indication of nutritional content, although one pound of naturally flavored drink boxes has different nutritional composition than one pound of fresh produce. If success is measured in terms of quantity, then this will be the criterion that drives emergency food provisioning. Charities are easy targets for critique; they often operate on a shoestring, use labor with different levels of knowledge and experience, and much of the time are put in a financially and socially powerless position, at the whims of donors. One result is that nonperishable or lowperishability items are preferred (Tiehen, 2002; Verpy, Smith, & Reicks, 2003); these last longer and do not require refrigeration. Their long shelf life means handling and transport is not timesensitive. These products cost less and are more likely to be donated. Nutrient-poor foods are less healthy overall (Monsivais & Drewnowski, 2007); previous food pantry investigations discovered the poor nutrient composition of donated items, especially in regards to adequate levels of calcium, vitamin A, and vitamin C (Akobundu, Cohen, Laus, Schulte, & Soussloff, 2004; Irwin, Ng, Rush, Nguyen & He, 2007). Donating large amounts is important since donation quantity is prioritized by agency recipients. Rock, McIntyre, and Rondeau (2009) found a misalignment between donor intent and client preference indicative of the "ignorance among food-secure people of what it is like to be food-insecure" (p. 167). Food banks and food pantries are pressured to accept foods on unfair grounds, just as clients are pressured to accept whatever food is handed to them. In at least one other case, food pantry donors "did not consciously consider nutrition when deciding which foods to donate" (Verpy et al., 2003, p.12). A demand-side perspective of private emergency food provisioning reveals somewhat complementary conditions that support the acquisition and distribution of low-quality foods. The longterm health consequences associated with the consumption of low-quality foods can be overlooked to satisfy immediate food needs, thereby reinforcing the value placed on the low-quality supply being donated. While expenses like shelter, heat, and medical expenses are relatively inelastic, food is flexible and can be adjusted based on these demands. On a limited budget, it is often the case that whatever money is leftover is used for food (Furst, Connors, & Bisogni, 1996; McEntee, 2010). As reported by McEntee, a homeless shelter resident commented: It's likes this, your oil's almost out, your electricity's high and they're going to shut it off, what are going to do? Well, we're going to have to cut down on our food budget. Do what you gotta do. . . you can buy your family packs and suck it up and eat ramen noodles. (McEntee, 2010, p. 795) Sometimes these types of food are chosen out of necessity (that is the only type of food offered) and other times it is out of habit (they are used to eating it).2 With the recent recession in the U.S. economy, purchases of cheap, ready-to-eat processed foods have increased. An Associated Press article entitled, "ConAgra Foods 3Q profit rises, maintains outlook" (Associated Press, 2010, para. 1) states: Strong sales of low-priced meals such as Banquet and Chef Boyardee and lower costs pushed ConAgra Foods Inc.'s third-quarter profit up 19 percent. Cheap prepared foods like those that ConAgra offers have appealed to customers during the recession as they look for ways to save money and eat at home more. Methods and Research Setting Approximately 7.7 percent of New Hampshire's population is food-insecure (Nord, Andrews & Carlson, 2008); 8 percent of the state's population lives in poverty, while 9.4 percent of Grafton County's population lives in poverty (U.S. Census Bureau, 2008). Grafton County was selected as the research site based on proximity to researchers as well as the existence of food insecurity. Grafton County (figure 2) has a population of 81,743 and a population density of 47.7 people per square mile (18.4 people per square kilometer) (U.S. Census Bureau, 2008). Unlike the other two primarily rural northern counties of New Hampshire (Carroll and Coos counties), Grafton County contains two universities that serve as educational and cultural centers (Dartmouth University in Hanover and Plymouth State University in Plymouth). Accordingly these areas attract residents with above-average educational attainment and income, thus offering a variegated set of social and economic conditions which are differentiated from the rest of the county. There are 14 registered food pantries in Grafton County (of a total of 165 in New Hampshire) (New Hampshire Food Bank, 2010). In 2012, there were 92 SNAP-authorized stores within the county, marking a 13 percent increase from 2008 (USDA FNS, 2012a). Approximately 16 percent of students were free lunch eligible in 2008 (USDA FNS, 2012b). In terms of local food potential, there were 10 farmers' markets in 2010 (USDA AMS, 2012) with 3.3 percent of farm sales attributable to direct to consumer sales ; U.S. Census of Agriculture, 2012). A purposive sampling method (Light, Singer, & Willett, 1990) was used to identify respondents (N = 16) who work regularly in Grafton County's PEFS. This included state employees, although the majority were workers and volunteers at food banks, soup kitchens, food pantries, and homeless shelters. These respondents were selected based on their above-average knowledge about hunger, food insecurity, and private emergency food provisioning in Grafton County (beyond their personal experience). Although some questions were specific to the respondent's area of expertise, the same general open-ended question template was used to facilitate informative discussion on topics related to food access, such as affordability, nutrition, and food provisioning (see table 1). The one-on-one semistructured interviews (Morgan & Krueger, 1998) with this group of respondents lasted between 60 and 90 minutes and took place in an office setting, community center, or over the phone (when in-person meetings were difficult to arrange). All interviews were recorded, transcribed, and coded. Participant observation (Flowerdew & Martin, 1997) was conducted at a Plymouth-area soup kitchen that served weekly hot meals for free to attendees. Data from interviews as well as field notes were coded and analyzed using NVivo, qualitative analysis software ( QSR International, 2010). After data was cleaned, data was examined as a whole to gain a general sense of overall meaning and depth. Open coding was undertaken, where material was organized into groups or segments of related information (Rossman & Rallis, 1998). We developed a qualitative codebook for efficient and consistent code assignment. Codes were examined, as well as the overall corpus of information. We identified underlying themes based primarily on respondent narratives. Over time, themes and trends emerged. Overlaps and differences between themes were identified, thus allowing their properties to be refined, ultimately resulting in progressively clear theme categories. Following theme assessment, interconnections and relations between themes were identified through concept mapping and triangulation (Fielding & Fielding, 1986). The authors conducted all interviews and observation, processed all data, and conducted all analysis. Institutional Review Board approval was obtained and all standard research protocols used. Findings from Grafton County Some of the data emerging out of the Grafton County case echoes previous observations about the PEFS. The preliminary data we present in this article is the product of field work, policy evaluation, and literature review. We do not claim that these findings are externally generalizable, although we do see similarities between our observations and those of other researchers, indicating that our data may be indicative of trends elsewhere, especially in rural areas of the northeastern United States where similar demographic and cultural traits exist. In this way, we also see potential in terms of research trajectories and policy reforms for those looking to build capacity between the PEFS and the local food system. Reliance upon Volunteers In relation to the existing criticisms that the PEFS is actually serving a long-term and sustained need and not a short-term or emergency one, many food pantry workers indicated that longterm usage by clients was common. For instance, one pantry worker explained that "most of the people that come in here are...I don't know if I would say chronic, but regulars" (0607).3 In these pantries, representatives talked about getting to know clients over the course of months and years of use; some clients stay and talk with pantry workers for emotional support during food pickups. This long-term usage has been critiqued and connected to the fact that the PEFS is so heavily reliant upon volunteer labor that resultantly there are opportunities for inconsistencies to develop (Lipsky, 1985; Molnar et al., 2001). Ad hoc administration of private emergency food distribution has consequences, such as inconsistent eligibility requirements and quality control (Daponte & Bade, 2006). In Grafton County pantries, eligibility was determined through a combination of criteria, such as pantry worker's personal judgment and preset income criteria. In one large pantry, more refined conditions were followed by staffand volunteers. In this pantry, if it was a client's first visit, then they were allowed to get food no matter what. However, in order to get food on subsequent visits they would need to bring proof of income (their income had to be below a certain amount based on number of household members). The director of this pantry explained, "the only time I turn them away is if they're using the other food pantries....Most of the time they trip themselves up" (0505). When asked about the consequences of using more than one pantry, the same respondent said, "I turn them offfor a whole year....To me, that's stealing food because that's government food involved in both places" (0505). This was not a set rule or policy of the pantry, but a guideline created by the director. Another worker explained that clients needed to fill out a TEFAP form (which determines eligibility under the rubrics of "Program" (already receiving a form of public assistance) and "Income" (one-person weekly income at or below USD370)), but that "it [the form] doesn't turn anybody away" (1215). The downside of a more subjective, informal system is that pantries can be run in a potentially inequitable manner (Daponte & Bade, 2006). In addition, a client who offended a staffmember or volunteer in the past will not be safeguarded against as they would be in a government-run system. A pantry director from a small church-run pantry was asked about assistance eligibility and replied that: We don't ask a lot of questions...We don't take any financial information and you don't need to qualify. I just tell people, "if you need it, you can use it."...You can tell by looking at them, you know? The car they drive, their clothes, you could tell they're not living high offthe hog, so to speak. (0607, emphasis added) In New Hampshire, 92 percent of food pantries and 100 percent of soup kitchens use volunteer labor, while 64 percent of pantries and 46 percent of soup kitchens rely completely on volunteer labor (Feeding America, 2010b). Volunteers partnered with pantry staffto perform tasks. Food has to be inspected, sorted, organized, and in some cases cleaned before it is handed out; how these tasks are carried out varies by pantry. In all pantries visited as part of this research, clients waited in line with other recipients (visible to each other) where nonpantry visitors to the agency could see them openly. In one venue, while pantry clients picked their food from a closet in a church, people working to set up a church dinner worked in the same room; these individuals and the pantry clients were visible openly to each other. These patterns show that by engaging in this private form of food assistance, clients give up any right to confidentiality they may be afforded through other forms of assistance, such as those offered by federal or state forms of food assistance. Another consequence of reliance on volunteer labor is that food standards are frequently disregarded. A set of pantry workers explained how they went to great lengths to utilize some squash donated from a nearby farm: We discovered a couple years ago that he can't keep it here [the pantry] because it will spoil...and then I said I'll take it, I got a place....So now I've got squashes and I keep an eye on them to make sure they aren't spoiling....So I have a room downstairs [in her house] that has no windows and it's about 55 [degrees]. And I put them down in the basement and then I bring them up into the garage and they're stored in the garage where it doesn't freeze. (0506) Pantry and food bank workers often clean and repackage food that is inconveniently packaged (e.g., in bulk) or has been broken open.4 These findings not only underscore the role of volunteer subjectivity, but they more broadly illustrate the negative externalities that can emerge in this unregulated system. Food Preferences: "Change Your Taste Buds" Depending on the agency, food preferences of clients may have minimal influence over foods received. Nutritional, cultural, or taste preferences can be disregarded, while pantry staffbeliefs dictate allotments. A volunteer who worked at a pantry and soup kitchen and also served on the board of the pantry said, "the younger ones [clients] are very, very fussy, they are turning their nose up at different things....Whereas if you're hungry, you accept and you learn to do it and change your taste buds" (0506, emphasis added). In the same interview as the one quoted above, this respondent reflected that "we're a spoiled society" and "there's a lot of honest need, but I think there's also those that are needy who don't help themselves" (0506). This respondent seems to believe that clients should be thankful for whatever they get, no matter what, since it is better than nothing. This is similar in a sense to how pantries are pressured into being thankful for all donations out of fear that refusal of items would jeopardize future giving (for an example, see Winne (2005)). Believing that clients should "change their taste buds" to accommodate the food available at the pantry food represents a misalignment between clients' nutritional well-being and the pantry objective of efficiently distributing all donated food. This respondent held a position of power within the pantry and was able to make managerial-level decisions. Following through on her sentiments means that clients should adjust their personal taste preferences to whatever donors decide to donate. Client preferences are interpreted by pantry staffin number of ways; consider the experience of this employee who worked at a smaller pantry in a northern part of the county: I had a guy call me today and wanted me to take his name offthe list here and I said "OK." I said "did you get a job?" I know he was looking for a job, "no, but I can't eat that crap." He said, "I like to eat organic now, natural food." He said, "I can't eat this stuff, processed kind of food." He said, "not that I don't appreciate what you're doing for me, but I just can't eat that kind of food." I said, "well, get a job" or that's what I felt like saying....Do you know how much that stuffcosts? We're not the end all, we're just supplemental here, we can't provide food for you for the week. I mean its just not going to happen. (0607) This employee appeared offended by this man's decision to stop accessing the pantry. By participating in the PEFS, these individuals relinquish rights and standards they may have in the public retail sphere (i.e., where federally and state enforced food safety regulations are upheld) and as a result are forced to gamble on the whims of the largely unregulated PEFS . This removal of food rights places food-insecure individuals in an even more food-precarious state, disempowering them beyond that which is accomplished through retail markets. One pantry worker explained that when individuals donate food, "lots of times it's ramen noodles because you can donate a lot at a low price" (0709). Food-pantry representatives working with a food-insecure population indicated that this group prefers quick and easy meals in the form of processed products, and also lacks adequate knowledge about nutrition and cooking to make informed food selections. Simultaneously, those accessing pantries revealed that food was a flexible budget item that could be adjusted according to the demands of other expenses. This often leads to trading down of items purchased - from more expensive, healthy items to cheaper, less healthy items. Food pantry representatives commented on how clients, especially young ones, prefer quick and easy products because "it's so much easier to open a can...things that are quick" (0506). Another pantry worker commented that "it's great when they say they cook....It just makes it so much easier to give them bags of nutritional food, but sometimes they'll just want the canned spaghetti, macaroni and cheese, hot dogs...foods that are easy to prepare for families," which she acknowledged as "a problem" (0709). Efforts to reform these eating habits were evident; one pantry worker reflected on how they had tried to switch from white to wheat bread, but found that "the wheat bread was not a hit" (1215). A nutrition professional working at a nonprofit described an attempt to change her clients' eating habits. She explained that her efforts were aimed at making people more nutritionally informed by showing them that eating healthier can be more affordable: We will do a comparison and we will make a meal with Hamburger Helper and we'll make basically homemade Hamburger Helper....I'll do a comparison of what Hamburger Helper costs and what it costs to make it from scratch. It's always of course cheaper to make it from scratch and then we do a taste test. And unfortunately many of the people have grown up with Hamburger Helper so that's what they like....They don't see the difference; how salty and awful it tastes....We'll do a whole cost analysis and they'll see it's about 59 cents a serving if you make it from scratch compared to about 79 cents a serving for Hamburger Helper. (1013) Another pantry worker explained: I think it's pricing, but then we have people, you know I believe it comes from how you grew up. You know, a lot of people shop the way their moms or dads shopped. And some people were just brought up on frozen boxed food and not cooked homemade meals and so that's all they know how to purchase. (0303) This may explain why pantries experience a demand for these easy-to-cook processed foods. While some pantries might push more nutritional options, others send contradictory nutritional messages. Not far from where the abovementioned nutritional professional worked, another pantry worker at the same agency remarked that "the stuffthat's easy for us to get is pasta, canned stuff, pasta mixes, and it's not highly nutritional....Tuna or some kind of a tinned meat, you know, with a Tuna Helper, that's the kind of stuffwe get here because we don't have any way to give them fresh meat" (0607). The food being donated is free for the pantry and free for the clients, made possible through private, often corporate donors. This represents a seemingly collaborative alignment between the need to dispose of unwanted food on behalf of corporate donors and the need for foodinsecure clients to consume food, yet this arrangement is rooted in a short-term outlook and power imbalance where corporate food entities are able to dump unwanted food for free upon a foodinsecure population, thereby realizing short-term profit gains (for the business) at the cost of longterm health of food-insecure individuals and its effect on governments. Assessing Collaborative Potential The rural PEFS appears to be similar to the urban PEFS in a number of ways. It is heavily reliant upon volunteer labor and it serves a significant proportion of the population, often on a regular basis. In the rural context there is a dispersed population. While centralized population centers like cities provide efficient and short-distance transportation networks, rural networks are decentralized with people living in remote areas, often requiring automobile access. This has a few practical consequences. A dispersed population also means that community food-growing opportunities like neighborhood gardens are more difficult to organize and implement when compared to a city where a group of neighbors can have a small vegetable plot within walking distance. Contrastingly, in many rural places the transportation cost of getting to a community space where a garden may be located represents another financial and logistical barrier. Cities are also places where people can more easily congregate to meet and organize reactive and proactive responses to inadequate food access (for example, to grow a neighborhood garden in response to being located in a "food desert"). In urban areas for instance, these have manifested in food justice efforts. In rural areas, the PEFS is the chief response to hunger and food insecurity (in addition to federal and state mandated programs). However, the rural PEFS operates on a smaller scale with fewer numbers of people accessing it and a high degree of malleability. As described earlier in this essay, this informality has been criticized; however, this ability to adapt means that individuals who operate PEFS entities (like food pantries) can take advantage of opportunities without having to obtain approval from higher levels of bureaucracy. In addition, the rural PEFS is often located where the land, soil, water, and air resource base for growing food is abundant. In contrast to the literature that supports the claims that low-income populations prefer processed foods (Drewnowski & Specter, 2004), data from the Grafton County case shows that in the pantries that were able to obtain small amounts of fresh, perishable foods (meats and fresh fruits and vegetables), these quickly became the most popular items. As one pantry worker explained: Most people know that an apple is healthier than a hot dog, but those [hot dogs] are way cheaper, you know, not that they're the same in any way....Here [at the food pantry] they would go for the things that they don't normally get their hands on, which is why those dairy products go fast and those veggies go fast. But I think in general when they are shopping they go for the cheapest, easiest thing to get through to the next week. (1215) In another study of Grafton County, a food pantry employee described how a local hunter donated moose meat: Interviewer: What are the most popular items that you have here in the pantry? Respondent 1: Meat. It's the most expensive... Respondent 2: Oh, was it last year we got the moose meat? We got 500 pounds [230 kg]. And we're thinking, what are we gonna do with all this moose meat? And it flew out of here. I mean, people were calling us and asking us for some. (McEntee, 2011b, p. 251) A key question emerging from this research is, "how do we harness the assets of both the PEFS and local food system to better serve the needs of food-insecure populations?" There is a demand for locally produced produce and meat on behalf of food-insecure individuals (as others have shown; see Hinrichs and Kremer (2002)). The desires of low-income consumers to eat fresh meat and produce (which often is locally produced) as well as to participate in some local food production activities (whether it be hunting or growing vegetables) have been overlooked by researchers. People accessing the PEFS in rural areas are accessing pantries, but also growing their food because it is an affordable way to obtain high-quality food they may otherwise not be able to afford (McEntee, 2011b). Based on the information provided in this article, potential synergies between the PEFS and the local food system in the rural context exist. Specifically, a traditional localism engages "participants through non-capitalist, decommodified means that are affordable and accessible" where "food is grown/raised/hunted, not with the intention to gain profit, but to obtain fresh and affordable food" (McEntee, 2011, pp. 254-255). Traditional localism allows for local food to become an asset for many food-insecure and poor communities that are focusing on the need to address inadequate food access. How could the rural PEFS source more food locally, thereby strengthening the local economy? How could private emergency food entities like food pantries and local food advocates promote food-growing, food-raising, and hunting activities as a means to increase grassroots, local, and affordable access to food? Like many places throughout the U.S., Grafton County is home to small-scale local agriculture operations supported by an enthusiastic public and sympathetic state. Simultaneously, there is the presence of food insecurity and a PEFS seeking to remediate this persistent problem. The actual structure of the PEFS could be thoroughly assessed (beyond the borders of Grafton County). If warranted, this system could be redesigned to prioritize privacy and formalize procedures in terms of ensuring that client food choices are respected. A crucial next step in reforming this system to benefit lowincome and minority clients is to emphasize the ability to grow, raise, and hunt food for their own needs5 through the traditional local concept. This would represent a transformation in which these activities could not only be supported by the PEFS, but also draw upon the social capital of communities in the form of memories and practices of rural people from the near past, all while reducing reliance upon corporate waste. If traditional local efforts were organized on a cooperative model, based on community need and not only the needs of individuals, it would benefit all those participating, drawing on collective community resources, such as food-growing knowledges and skills, access to land, and tools, thereby enhancing the range of rural livelihood strategies. In this sense, these activities are receptive to racial and economic diversity as well as alliance-formation across social groups and movements, all of which are characteristic of the food sovereignty movement (Holt- Giménez & Wang, 2011). In moving forward additional research is needed. While our findings highlight potential shortcomings, there is a lack of data exploring the rural PEFS experience. Specifically, from the demand side, we need more data about the users of this system, specifically in regard to their satisfaction with food being given to them. Are they happy with it? Do they want something different that is not available? Do they lack the ability to cook certain foods being handed out by the pantry? Feeding America's Hunger in America survey asks about client satisfaction; in its 2010 report, only 62.7 percent of surveyed clients were "very satisfied" with the overall quality of the food provided.6 Additionally, the fact that this survey is administered by the same personnel who are distributing food donations raises methodological biases. More needs to be discovered about why such a large proportion of users is not "very satisfied." From the supply side, we need to know more about food being distributed and its nutritional value. Currently, the food being donated and distributed is unregulated to a large degree, especially in rural pantries. Also on the supply side, the source of food provided to Feeding America as well as individual state food banks and food pantries needs to be inventoried with more information beyond just its weight. Knowing the quantity of specific donated products as well as the financial benefit (in terms of tax write-offs) afforded to donors would add transparency. Conclusion: Neoliberal Considerations and Future Directions The findings we have presented in this article are intended to reveal important policy questions about the PEFS and local food movement; we do acknowledge, however, that it also has raised some important questions. In summary, we see opportunities to move forward in enacting a food sovereignty agenda with both local and global scales in mind. First, value-added, market-based local solutions used to address the inadequacies of the current food system are immediately beneficial. However, these should not be accepted as the endall solution. Looking beyond them to determine what else can be accomplished to change the structure of the food system to shiftpower away from oligarchic food structures of the corporate food regime to food citizens, not only food consumers, would result in systemic change. A key consideration in realizing any reform in the PEFS, and simultaneously challenging and transforming the unsustainable global food regime, is recognizing the neoliberal paradigm in which government and economic structures exist. Neoliberalism can be defined as a political philosophy that promotes market-based rather than state-based solutions to social problems, while masking social problems as personal deficiencies. The PEFS is essentially acting as a vent for unwanted food in this system that also provides a financial benefit to the governing food entities (i.e., food businesses). Too often alternatives are hailed as opposing the profit-driven industrial food system simply because they are geographically localized; in reality, they may re-create the classist and racist structures that permeate the larger global system.7 The PEFS is an embedded neoliberal response to food insecurity; while public-assistance enrollment is on the rise, so is participation in the PEFS. This is a shiftin responsibility in who is providing assistance to food-insecure populations from the government to the private sector. In this sense it is a market-based approach to addressing food insecurity (i.e., by dumping food on the private charity sector, market retailers cut their own waste disposal costs), and the result is continual scarcity and the establishment of a system that reinforces the idea that healthy food is a privilege, only accessible to those with adequate financial and social capital. Along these same lines, a form of food localism exists that is arguably detrimental to those without financial and social capital; these efforts have and continue to frame food access solely as an issue of personal responsibility related to economic status and nutritional knowledge (a narrative thoroughly discussed by Guthman (2007, 2008)). This prioritizes market-based solutions to developing local food systems as well as universal forms of food education that emphasize individual health. As Alkon and Mares (2012) explain, Neoliberalism creates subjectivities privileging not only the primacy of the market, but individual responsibility for our own wellbeing. Within U.S. food movements, this refers to an emphasis on citizen empowerment, which, while of course beneficial in many ways, reinforces the notion that individuals and community groups are responsible for addressing problems that were not of their own making. Many U.S. community food security and food justice organizations focus on developing support for local food entrepreneurs, positing such enterprises as key to the creation of a more sustainable and just food system. The belief that the market can address social problems is a key aspect of neoliberal subjectivities. (p. 349) Though elements of both the PEFS and the local food system have arguably been folded into neoliberalization processes through market-based mechanisms, incremental steps to change these dynamics are possible. Reframing issues of food accessibility (including food insecurity, hunger, food deserts, etc.) as issues of food justice moves us beyond an absolute spatial understanding of food issues. For instance, when we only look at physical access to food, we often disregard the more important considerations of class, race, gender (see Alkon and Agyeman, 2011), and sexual orientation that define a person's present position (and over which they often have no control) and which dictate how they engage with the food system. These considerations are present in current food-justice efforts, which seek to ensure that communities have control over the food grown, sold, and consumed there. Rural food justice has been defined using the traditional localism concept: Traditional localism in rural areas engages participants through non-capitalist, decommodified means that are affordable and accessible. Food is grown/raised/hunted, not with the intention to gain profit, but to obtain fresh and affordable food. A traditional localism disengages from the profit-driven food system and illustrates grassroots food production where people have direct control over the quality of the food they consume - a principal goal of food justice. (McEntee, 2011b, pp. 254-255) Utilizing this rural form of food justice involves more than promoting individual food acquiring techniques; it involves developing organizational and institutional strategies that improve the quality of food available to PEFS entities. This is currently accomplished by some, such as when pantries obtain fresh produce through farmer donations or when a food bank develops food-growing capacity. 8 But these types of entities are in the minority. The next stage of realizing food justice, we posit, is to determine how a food sovereignty approach can be utilized in a global North context. Food justice predominantly operates to find solutions within a capitalist framework (and it has been criticized as such) while food sovereignty is explicitly geared toward the dismantling of this system in order to achieve food justice. Regime change and transformation requires more than recognition and control over food-growing resources; it requires alliance and partnership-building between groups to "to address ownership and redistribution over the means of production and reproduction" (Holt- Giménez & Wang, 2011, p.98). Adopted by organizations predominantly located in the global South, food sovereignty is focused on the causes of food system failures and subsequently looks toward "local and international engagement that proposes dismantling the monopoly power of corporations in the food system and redistributing land and the rights to water, seed, and food producing sources" (Holt-Giménez, 2011, p. 324). There is an opportunity for people in the global North not only to learn from the global South food sovereignty movements, but to form connections and alliances between North and South iterations of these movements.9 As discussed above, the dominant food movement narrative is in sync with the economic and development goals of government (e.g., state-sanctioned buy-local campaigns) as well as marketing prerogatives of global food corporations (e.g., "local" being used as marketing label). Building a social movement powerful enough to place meaningful political pressure upon government to support a food system that prioritizes human wellbeing, not profit, is an immediate challenge. Incremental solutions are necessary in order to improve the lives of people now. However, these local solutions, such as innovative farm-to-school programming and other viable models between the local food environment and the PEFS that we have discussed in this article, would be more effective at affecting long-term systemic change if they were coupled with collective approaches to acknowledge and limit the power of the corporate food regime to prevent injustice, while also holding the state accountable for its responsibility to citizens, which it has successfully "relegated to voluntary and/or market-based mechanisms" (Alkon and Mares, 2012, p. 348). Food sovereignty offers more than an oppositional view of neoliberalism, however. The food sovereignty movement advances a model of food citizenship that asserts food as a nutritional and cultural right and the importance of democratic on-the-ground control over one's food. These qualities resonate with food-insecure and disenfranchised communities, urban and rural, in both the global North and South. Sidebar Citation: McEntee, J. C., & Naumova, E. N. (2012). Building capacity between the private emergency food system and the local food movement: Working toward food justice and sovereignty in the global North. Journal of Agriculture, Food Systems, and Community Development, 3(1), 235-253. http://dx.doi.org/10.5304/jafscd.2012.031.012 Copyright © 2012 by New Leaf Associates, Inc. Footnote 1 Cartesian understandings of space utilize a grid-based measurement of physical proximity. These types of proximitybased understandings of food access (i.e., food access is primarily a matter of bringing people physically closer to food retailers, as is promoted by the USDA Food Desert Locator) tend to overlook other nuanced forms of food access based on knowledge, culture, race, and class. 2 The amount of processed food, especially in the form of prepared meals and meals eaten outside the home, is steadily increasing in the United States (Stewart, Blisard, & Jolliffe, 2006). 3 The four-digit number indicates interview location and respondent IDs. 4 A leading antihunger effort in New Hampshire is the New Hampshire Food Bank (NHFB), the state's only food bank and a member of Feeding America. In 2008 the NHFB "distributed over 5 million pounds of donated, surplus food to 386 food pantries, soup kitchens, shelters, day care centers and senior citizen homes" (N.H. Food Bank, 2010). In total N.H. has 441 agencies registered with NHFB that provide food to 71,417 people annually. Grafton County has 18 food pantries, which "distribute non-prepared foods and other grocery products to needy clients, who then prepare and use these items where they live" and where "[F]ood is distributed on a short-term or emergency basis until clients are able to meet their food needs" (N.H. Food Bank, 2010). 5 A noteworthy example of an organization that has begun to accomplish these objectives is The Stop Community Food Centre in Toronto, which was recently described by Levkoe and Wakefield (2012). 6 The remaining categories are: "Somewhat satisfied" (31.3 percent), "Somewhat dissatisfied" (4.8 percent), and "Very dissatisfied" (1.3 percent). 7 For additional discussion of the political economic transition from government to governance, such as the transfer of state functions to nonstate and quasistate entities, see Purcell (2002). 8 An example of this type of effort is that of the Vermont Food Bank, which purchased a farm in 2008 in order to supply the food bank with fresh, high-quality produce as well as to sell the produce. 9 The U.S. Food Sovereignty Alliance has recognized the importance of building these coalitions: "As a US-based alliance of food justice, anti-hunger, labor, environmental, faith-based, and food producer groups, we uphold the right to food as a basic human right and work to connect our local and national struggles to the international movement for food sovereignty" (US Food Sovereignty Alliance, n.d., para. 1). 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Journal of Planning Education and Research, 23(4), 378-386. http://dx.doi.org/10.1177/0739456X04264886 Welsh, J., & MacRae, R. (1998). Food citizenship and community food security. Canadian Journal of Development Studies, 19, 237-55. http://dx.doi.org/10.1080/02255189.1998.9669786 Winne, M. (2005). Waste not, want not? Agriculture and Human Values, 22(2), 203-205. http://dx.doi.org/10.1007/s10460-004-8279-8 Winter, M. (2003). Embeddedness, the new food economy and defensive localism. Journal of Rural Studies, 19(1), 23-32. http://dx.doi.org/10.1016/S0743-0167(02)00053-0 Wu, C., & Eamon, M. K. (2007). Public and private sources of assistance for low-income households. Journal of Sociology & Social Welfare, 34(4), 121-149. AuthorAffiliation Jesse C. McEntee a Food Systems Research Institute and Tufts Initiative for the Forecasting and Modeling of Infectious Diseases Elena N. Naumova b Department of Civil and Environmental Engineering, Tufts University, and Tufts Initiative for the Forecasting and Modeling of Infectious Diseases Submitted 2 May 2012 / Revised 28 June and 26 July 2012 / Accepted 27 July 2012 / Published online 4 December 2012 aCorresponding author: Jesse C. McEntee, PhD, Managing Partner, Food Systems Research Institute LLC; P.O. Box 1141; Shelburne, Vermont 05482 USA; +1-802-448-2403; www.foodsystemsresearchinstitute.com; jmcentee@foodsri.com b Elena N. Naumova, PhD, Associate Dean for Research, School of Engineering; Professor, Department of Civil and Environmental Engineering, Tufts University; also Tufts Initiative for the Forecasting and Modeling of Infectious Diseases (InForMID) (http://informid.tufts.edu/); elena.naumova@tufts.edu Acknowledgments: The authors are grateful to the Economic and Social Research Council's Centre for Business Relationships, Accountability, Sustainability and Society at CardiffUniversity as well as the Center for Rural Partnerships at Plymouth State University for financial support during this research. The authors are also grateful to the three anonymous reviewers who provided constructive feedback on earlier drafts of this article. Word count: 11055Show lessYou have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimerNeither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer Translations powered by LEC.Translations powered by LEC. Copyright New Leaf Associates, Inc. Fall 2012More like this
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Both Hobbes and Locke describe human beings as equal in the state of nature. How do their understandings of equality in the state of nature differ?
This question works well to help students compare the ideas of Hobbes & Locke (which are part of what I ask students to think of as the "bookshelf" or perhaps today the twitter feeds, etc. of the founders)! When working with H.S. students, I find it is useful to ask them to point out specific evidence or passages from documents we are using to support their assertions. While this may go without saying for college students, high school students sometimes need that directive to help them develop that habit rather than offer a more "intuitive" contribution to the discussion or writing prompt.
For the high school student, many teachers (myself included) often ask the students early in the course to reflect upon, and define pivotal concepts such as "equality" to provide an anchor point before wrestling with what Hobbes, Locke, et. al have to say. It has been my experience that they are pleased with themselves any time their own thought process aligns with the political philosophers they are being introduced to. Any traction of that nature usually helps to encourage them to entertain the possibility that course content is relevant to their own lives.
Please advise if my suggestions regarding the high school classroom are not the direction you are seeking in this editing / reflection process.
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www.scielo.br www.scielo.br
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Richness
patterns of LENGTH and SHRINKAGE.
would this test for the hypothesis that older (longer) individuals are more likely to be shrunken because time is the greater explaining variable over location (locations may not be experiencing as much difference in fishing pressure as the sample distribution leads to believe. i.e. we are sampling the fishery well enough!? yay. (In healthy years would kelp abundance be significantly different among sites? (location significant?) this could indicate that whole system is uniformly ailing?) ..... I think there may be preliminary data that supports the idea that variously sized abalone (visible to divers) recovered or died from starvation over equal intervals. therefore, i'm thinking time, not some metabolic cost of being big, is the explainer for now. this is a well documented, multi-year stressed system.
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edu307class.networkedlearningcollaborative.com edu307class.networkedlearningcollaborative.com
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f we think of someone who is a fluent reader or speaker, we generally do not think of a person who speaks or reads fast. Rather, we are more likely to think of someone who uses their voice to help convey meaning to a listener when speaking or reading orally. (
This is one thing I definitely agree with. I don't really get the concept of "reading fast". I feel that when I "read fast" like in the manner they look for in those fluency tests I don't really take in all the details that I would normally look at while reading. This not only applies to reading but other subjects as well. I feel as though people should be allowed to go at their own pace so as to further their understanding as completely as possible. When I am orally reading out loud and fast it may sound fluent but honestly I am not comprehending as well as when I am silently reading at my own pace.
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transcripts.cnn.com transcripts.cnn.com
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But having said that too, I think the fact that he reaches out to a lot of people outside of the administration and I'm honored to be one of them, the fact that he reaches out to private citizens, I think is a strength of this administration, one of the reasons that we elected a businessman, the first entrepreneur President in American history, very different, very unorthodox, clearly has upset the swamp in a myriad of ways as we see, but I think also in positive ways, for instance, tax cuts and deregulation, what's going on in this country outside of the swamp, outside of the beltway, which is growth and optimism and security.
Hello, fact-checkers! This statement, taken from CNN interviews and discussions, may be worth your scrutiny. It was selected using ClaimBuster, a tool developed in the computer science department at the University of Texas at Arlington.
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www.cs.grinnell.edu www.cs.grinnell.edu
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Most scholars of hypertext of the time pointed to Vannevar Bush's 1945 article "As We May Think" as an important precursor to the Web and as providing important guidance for necessary development. Bush's model of hypertext was much richer than that of the early Web. Among other things, he envisioned people who would put together articles (or "trails") by finding a sequence of useful pages in different sources, annotating those pages, inserting a few pages of their own, and linking it all together. While the Web had "live links", those links were limited to the original authors of the text, so The Web provided essentially none of the features necessary for Bush's more collaborative model.
Great summary.
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hookandeye.ca hookandeye.ca
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Once you’ve created your masterpiece, you need to think about how you are going to print your books. The way we see it, you have three options:
As we’ve talked extensively about the importance of distribution in the comic book industry, this article offers unique insight into the production aspect of book publishing but I’m also curious about the distribution process (from the perspective of a small press) and the types of challenges it may run into.
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- Mar 2018
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edu307class.networkedlearningcollaborative.com edu307class.networkedlearningcollaborative.com
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The goals of the people in this small community could not be fully grasped through observations of their visible lives. Heath had to uncover their imag- ined lives as well to understand their perspectives on life, literacy, and edu- cation
This is important to think about as a teacher because our students may have so much more going on than visible to us. Although this quote is not saying that exactly, I think it is pointing out that we need to dig deeper than the surface and learn more than the basic information to truly understand.
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www.youtube.com www.youtube.com
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Complexity Theory - Dynamical Systems Theory
If we want to make change we should come at a problem from as many different areas as possible.
We should be wary of the magic bullet. Complexity theory may be seen as post-structuralist or even further?
This is part of an agency structure debate.
There are varied factors that contribute to change.
The connections of neurons are more important than the number of cells are more important for consciousness or the mind. This is a good analogy for why complexity theory is so essential.
Consciousness emerges when critical mass is reached in a system.
It's hard to know how much of a factor something can be in a causal system. For example, how much do we cause do we attribute to butterfly wings causing a storm in India.
What causes change in the education system?
We need to use words like compounding effects to explain change.
We need to conceive of change in terms of speed and direction, like a mathematical function.
We need to be wary of one dimensional change or one kind of initiative. You need to think of multiple factors.
Effective intervention means intervention from every possible angle.
We need to pump resources until we have autocatalysis.
International Journal of Education Development Mark Mason
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www.americanyawp.com www.americanyawp.com
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If anything praiseworthy is to be done, it must be done through unity, and it is for that reason that the Universal Negro Improvement Association calls upon every Negro in the United States to rally to this standard. We want to unite the Negro race in this country.
I think uniting together is a great way to keep their hopes and spirits strong. Individually they may not seem as much as a threat, but an organized group would surely make the white people at that time very uncomfortable.
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www.asatheory.org www.asatheory.org
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Critical realism is not an empirical program; it is not a methodology; it is not even truly a theory, because it explains nothing. It is, rather, a meta-theoretical position: a reflexive philosophical stance concerned with providing a philosophically informed account of science and social science which can in turn inform our empirical investigations. We might think of this in terms of three layers: our empirical data, the theories that we draw upon to explain our empirical data, and our metatheories—the theory and the philosophy behind our theories.While critical realism may be a heterogeneous series of positions, there is one loose genetic feature which unites it as a metatheory: a commitment to formulating a properly post-positivist philosophy. This commitment is often cast in the terms of a normative agenda for science and social science: ontological realism, epistemic relativism, judgmental rationality, and a cautious ethical naturalism.
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www.bartleby.com www.bartleby.com
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No doubt there is humorous exaggeration in this picture, but there is gross exaggeration in the frame of mind against which it was directed. You can not have omelettes without breaking eggs; you can not destroy the practises of barbarism, of slavery, of superstition, which for centuries have desolated the interior of Africa, without the use of force; but if you will fairly contrast the gain to humanity with the price which we are bound to pay for it, I think you may well rejoice in the result of such expeditions as those which have recently been conducted with such signal success in Nyassaland, Ashanti, Benin, and Nupé—expeditions which may have, and indeed have, cost valuable lives, but as to which we may rest assured that for one life lost a hundred will be gained, and the cause of civilization and the prosperity of the people will in the long run be eminently advanced. But no doubt such a state of things, such a mission as I have described, involves heavy responsibility. In the wide dominions of the queen the doors of the temple of Janus are never closed, and it is a gigantic task that we have undertaken when we have determined to wield the scepter of empire. Great is the task, great is the responsibility, but great is the honor; and I am convinced that the conscience and the spirit of the country will rise to the height of its obligations, and that we shall have the strength to fulfil the mission which our history and our national character have imposed upon us.
They are trying to justify the violence.
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We think and speak of them as part of ourselves, as part of the British Empire, united to us, altho they may be dispersed throughout the world, by ties of kindred, of religion, of history, and of language, and joined to us by the seas that formerly seemed to divide us.
A united British Empire
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www.insidehighered.com www.insidehighered.com
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Going all the way back to the Hermann Ebbinghaus “forgetting curve” experiments of the 1880s, we have known -- and replicated in dozens if not hundreds of experiments -- that no matter how serious, responsible and dedicated we professors are to “covering” our “topic,” students retain and apply subsequently only what is meaningful to them. I like to call this “haunted by the 8 percent.” In experiment after experiment, if you test students with basically matched backgrounds (say, from the same educational institution and major) who took a big introductory course on a topic (say, Psychology 101) six months in the past and compare their results with those of other students who never took the course, the differential in test scores is only about 8 percent. Here’s a variation: recently, at one of the nation’s elite private prep schools, students were given, with no warning, the exact same exams one September that they had taken as final exams the previous May. The average grade on finals was about A-minus/B-plus. On the September retests: F.
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medium.com medium.com
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Shaun King sees Marvel's Black Panther as a historically significant film.
It’s going to make well over a billion dollars and may actually do so within a month. From a pure business standpoint, it is to film what Michael Jackson’s Thriller was to music.
. . .
There is a movement we call Afro-Futurism, where we imagine a Black way of life free of white supremacy and bigotry. Black Panther, I think, is the first blockbuster film centered in the ethos of Afro-Futurism, where the writers, and directors, and makeup and wardrobe team all imagined a beautiful, thriving Black Africa without colonialism.
Wakanda showed us our families in one piece. No war on drugs. No mass incarceration. No KKK. No lynching. No racial profiling. No police brutality.
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blogs.baruch.cuny.edu blogs.baruch.cuny.edu
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I’d like to start out by proposing an analogy involving weapons. Weapons take on various forms and meanings throughout different mediums of use. When we think of the word “weapon” today, no doubt we think about the easily available lethal weapons of war such as the AR-15, an automatic riffle that has been the catalyst in so many mass shootings in America recently. What we may not immediately think about is how this particular weapon has been used to protect many American lives overseas.
I wonder if you can drop this analogy to modern time AR-15s altogether because it does not add much to the rest of your paper. My original thought was that you could perhaps bring this analogy back at end, right before your conclusion.
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ven more careful readers, wefear, will not take it to heart – or if they do, may not have much sense of what to doabout it – because the learning outcomes on which it focuses seem so abstractedfrom the daily life of teaching. Because of this gap between general skills anddisciplinary learning, each of us, while fascinated by Arum and Roksa’s powerfulresearch, has for different reasons found the results inAcademically Adriftsome-what at odds with her own experiences. We feel that it is important to take thisdissonance seriously, and would like to suggest that it arises from differences inwhere we look for student learning.
Heiland and Rosenthal agree a gap needs to be closed between general education skills and disciplinary skills but suggest we need to look for student learning in different places. I think experiential learning is one approach to creating learning opportunities that get both the student and the faculty engaged in assessment and the process of learning. Experiential learning within the disciplines could involve creating reflective writing assignments within the discipline that requires the student to examine their achievement within the discipline as well as the intersection of other general skills used in the learning activity. The authors suggest that faculty need to engage the general education skills within their own discipline through outcomes assessment efforts. I have observed faculty who have never received any training in this area or ever discussed it. Measuring the level of learning achieved by students using standardized tests seems very limiting and this is an area ripe for additional research. I think another approach to consider is how we get students and faculty to collaboratively measure the learning that they both know is occurring. It is interesting to note that as I reflect on the past year in this program I am experience the learning process but we rarely discuss it with each other or the faculty.
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press.rebus.community press.rebus.community
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Ironically, in this age, one may know much about a subject and yet know little about its ramifications. I for one know decent people who know everything about the chemistry of CFCs and nothing about the ozone layer (Nissani, 1996); everything about internal combustion engines and nothing about global warming; everything about minimum wage legislation and nothing about poverty. Compartmentalization, besides lack of education, is the enemy; an enemy that can only be conquered through holistic scholarship and education:
I think this stresses the importance of interdisciplinarity in all forms of educations. Since we are realizing this more and more hopefully it will lead to the evolution of humanity as a whole, as well.
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msu.edu msu.edu
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6Comparing their lives with those of their parents, people acknowledge that some things will be more difficult and others easier. By 49 percent to 30 percent, they think they will have more difficulty than their parents did in finding the money to put kids through college and by 41 percent to 32 percent they think owning a home will be more difficult. Conversely, however, by 47 percent to 14 percent, they believe it will be easier for them to be in good physical health. Of equal importance, by 44 percent to 16 percent they think it will be easier to have an interesting job and even easier (by 42 percent to 31 percent) to earn enough money for a good living. [18]These findings show that Americans today realize that they are better off in many ways than their parents were. But at the same time, they are aware that many of the new values and lifestyles threaten the family -- an institution that has come to mean more to them now that it can no longer be taken for granted.The Meaning of SuccessOne of the most sweeping changes in postwar American cultural values relates to the meaning of success. In the 1950s Americans shared a certain definition. Success meant getting married, raising children who would be better off than oneself, owning a home and an automobile, and working one's way up the ladder of social mobility. The trappings of success were largely external and material, a matter of keeping up with the Joneses.When in November 1962 Gallup queried cross-sections of the public on the "formula for success in today's America," two answers dominated all others: get a good education (50 percent) and work hard (31 percent), followed by honesty and integrity (17 percent). Only 6 percent mentioned having a job that one enjoys doing, and a paltry 3 percent cited the importance of self-confidence and self esteem.Then came the 1960s campus rebellion and its iconoclastic attitudes toward the 1950s. For millions of college students the shared meaning of success shifted from owning a Cadillac to fulfilling one's unique inner potential.In the 1970s the majority of Americans were intrigued but still unconvinced of the virtues of the new outlook. A January 1971 Harris poll asked people, "Do you think the desire on the part of many young people to . . . turn their backs on economic gain and success . .. is a healthy or unhealthy thing?" Only 13 percent thought it healthy. In mid-decade (April 1974) the leading responses to a Gallup question about "what really matters in your own life," were a decent and better standard of living (31 percent), good health (25 percent), adequate opportunities for one's children (23 percent), a happy marriage and family life (15 percent), and owning one's own home (12 percent) -- all traditional, fifties-like conceptions.By the 1980s, however, most Americans were attempting to graft the new values onto the old ones. In response to a May 1983 Gallup question about which factors are most important for "personal success in America today," the top ranking ones were good health (58 percent), a job one enjoys (49 percent), a happy family (45 percent), a good education (39 percent), peace of mind (35 percent), and good friends (25 percent). Note that the traditional emphasis on education and family remains an important part of the definition of success, but newer values such as having a job one enjoys, peace of mind, and good friends have now been elevated to a status equal to or higher than the traditional ones. It is characteristic of the 1980s that people wanted material well-being and the new forms of inner fulfillment extolled in the 1960s and 1970s.[19]Now in the 1990s we are witnessing a further evolution of the shared meaning of success. Increasingly, Americans are coming to think of success as self-defined rather than conformity to the expectations of others. Over a five-year period, the DYG SCANSM has measured a significant increase in the ratio of those embracing a conception of success as self-defined. By 1987 it had already reached a 5:1 ratio (63 percent to 12 percent), and by 1991 it had grown to more than a 7:1 ratio (68 percent to 9 percent).[20]There are some modest demographic differences, mainly related to age and income. People between 40 and 60 with higher incomes (above $50,000 a year) lean slightly more often toward the self-defined measure of
I agree
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erinbartram.com erinbartram.com
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But let’s be honest: most graduate programs in history are preparing students to be history professors. We can talk all we want about alt-ac careers, but when it comes down to it, few of them actually require a PhD, and almost none of them need you to have learned as much as I’ve learned about the day-to-day operations of rural 19th century parishes
True, one of the huge shortcomings of our grad programs is that they approach our training as PhDs in terms of professional programs like law school (i.e. you are trained for a very specific job). But I think you can give yourself more credit about the fact that your training was only partly about gaining knowledge/content. You aren't just a receptacle of specialized knowledge: a lot of this knowledge you produced yourself through really useful skills. You are an expert researcher, you can manage and synthesize lots of info on a variety of topics, analyze it and come up with impactful insights, create engaging narratives, and analyze a lot of different contemporary cultural problems using your skills and specialized knowledge (after all, it may be cliche but the past is essential to understanding and addressing the present). Positioning yourself as a kind of repository of knowledge/content belies the fact that you actively produced that knowledge and are capable of producing knowledge on a lot of other topics in a variety of contexts (and a hell of a lot quicker than people not trained to do this!).
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www.psychologytoday.com www.psychologytoday.com
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the average person seeking help has tended to seek psychiatric drugs rather than psychotherapy. Antidepressants and antianxiety medications are among the leading prescription drugs not only in the US but around the world (link is external). We think nothing of getting a prescription filled for one of these psychotropic medications that we may obtain, without much consultation, from a medical professional. However, you should be concerned that these drugs may not only fail to treat your psychological symptoms but can have a host of adverse side effects.
This society tends to think that medications are the answer to everything. As a society, we fail to remember that medications have several different side effects. Using psychotherapy instead of these medications is a better option because you are able find a solution to your mental illness without having to face any side effects.
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openlab.citytech.cuny.edu openlab.citytech.cuny.edu
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The shock of photographed atrocities wears off with repeated viewings, just as the surprise and bemusement felt the first time one sees a pornographic movie wear off after one sees a few more. The sense of taboo which makes us indignant and sorrowful is not much sturdier than the sense of taboo that regulates the definition of what is obscene. And both have been sorely tried in recent years. The vast photographic catalogue of misery and injustice throughout the world has given everyone a certain familiarity with atrocity, making the horrible seem more ordinary — making it appear familiar, remote (“it’s only a photograph”), inevitable. At the time of the first photographs of the Nazi camps, there was nothing banal about these images. After thirty years, a saturation noint may have been reached. In these last decades, “concerned” photography has done at least as much to deaden conscience as to arous it.
Photography as we see it, changes the way we think, like any other technology that we have today.
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ds-pages.swarthmore.edu ds-pages.swarthmore.edu
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Finally it must be stressed that the discrimination of which we complain is not simply discrimination against poverty and ignorance which the world by long custom is used to see: the discrimination practiced in the United States is practiced against American Negroes in spite of wealth, training and character.
I think this passage is really important because a lot of his text seems to be underselling the role that race plays in, well, racism. Du Bois places so much emphasis on the economic causes of racism that one could almost get away with thinking that race is simply incidental to the problem. He reminds us here that although the origins of racism may be economic, its oppression is not limited according to economics; all black people are discriminated against, no matter their economic or educational status. And although racism may harm the white man as much as the black man, it is clearly directed against the black man, for no other reason than the color of his skin.
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successful effort to achieve, to deserve
This phrasing really stuck with me... in the language of international human rights we presume all humans to inherently deserve rights by virtue of being human. Here, however, DuBois positions Black Americans as successfully "achieving" a demonstration of how greatly they deserve human rights through their actions and self-advocacy. Maybe I'm reading too much into this, but I would love to hear what others think about what DuBois may be insinuating about the paradox of human rights at large.
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- Feb 2018
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press.rebus.community press.rebus.community
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we may need to break the question up into parts and look at study time, social life, living away from home, economic issues, mental health, oppression, and more. Studying these parts will help us get a sense of the overall reasons for the problem.
I think lower education such as high school does nothing to prepare students for college and you learn everything in your first semester
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www.gutenberg.org www.gutenberg.org
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I put it in the coffin. It was in there when you was crying there, away in the night. I was behind the door, and I was mighty sorry for you, Miss Mary Jane.” It made my eyes water a little to remember her crying there all by herself in the night, and them devils laying there right under her own roof, shaming her and robbing her; and when I folded it up and give it to her I see the water come into her eyes, too; and she shook me by the hand, hard, and says: “Good-bye. I'm going to do everything just as you've told me; and if I don't ever see you again, I sha'n't ever forget you and I'll think of you a many and a many a time, and I'll pray for you, too!”—and she was gone. Pray for me! I reckoned if she knowed me she'd take a job that was more nearer her size. But I bet she done it, just the same—she was just that kind. She had the grit to pray for Judus if she took the notion—there warn't no back-down to her, I judge. You may say what you want to, but in my opinion she had more sand in her than any girl I ever see; in my opinion she was just full of sand. It sounds like flattery, but it ain't no flattery. And when it comes to beauty—and goodness, too—she lays over them all. I hain't ever seen her since that time that I see her go out of that door; no, I hain't ever seen her since, but I reckon I've thought of her a many and a many a million times, and of her saying she would pray for me; and if ever I'd a thought it would do any good for me to pray for her, blamed if I wouldn't a done it or bust. Well, Mary Jane she lit out the back way, I reckon; because nobody see her go. When I struck Susan and the hare-lip, I says: “What's the name of them people over on t'other side of the river that you all goes to see sometimes?” They says: “There's several; but it's the Proctors, mainly.” “That's the name,” I says; “I most forgot it. Well, Miss Mary Jane she told me to tell you she's gone over there in a dreadful hurry—one of them's sick.” “Which one?” “I don't know; leastways, I kinder forget; but I thinks it's—” “Sakes alive, I hope it ain't Hanner?” “I'm sorry to say it,” I says, “but Hanner's the very one.” “My goodness, and she so well only last week! Is she took bad?” “It ain't no name for it. They set up with her all night, Miss Mary Jane said, and they don't think she'll last many hours.” “Only think of that, now! What's the matter with her?” I couldn't think of anything reasonable, right off that way, so I says: “Mumps.” “Mumps your granny! They don't set up with people that's got the mumps.” “They don't, don't they? You better bet they do with these mumps. These mumps is different. It's a new kind, Miss Mary Jane said.” “How's it a new kind?” “Because it's mixed up with other things.” “What other things?” “Well, measles, and whooping-cough, and erysiplas, and consumption, and yaller janders, and brain-fever, and I don't know what all.” “My land! And they call it the mumps?” “That's what Miss Mary Jane said.” “Well, what in the nation do they call it the mumps for?” “Why, because it is the mumps. That's what it starts with.” “Well, ther' ain't no sense in it. A body might stump his toe, and take pison, and fall down the well, and break his neck, and bust his brains out, and somebody come along and ask what killed him, and some numskull up and say, 'Why, he stumped his toe.' Would ther' be any sense in that? No. And ther' ain't no sense in this, nuther. Is it ketching?” “Is it ketching? Why, how you talk. Is a harrow catching—in the dark? If you don't hitch on to one tooth, you're bound to on another, ain't you? And you can't get away with that tooth without fetching the whole harrow along, can you? Well, these kind of mumps is a kind of a harrow, as you may say—and it ain't no slouch of a harrow, nuther, you come to get it hitched on good.” “Well, it's awful, I think,” says the hare-lip. "I'll go to Uncle Harvey and—” “Oh, yes,” I says, “I would. Of course I would. I wouldn't lose no time.” “Well, why wouldn't you?” “Just look at it a minute, and maybe you can see. Hain't your uncles obleegd to get along home to England as fast as they can? And do you reckon they'd be mean enough to go off and leave you to go all that journey by yourselves? you know they'll wait for you. So fur, so good. Your uncle Harvey's a preacher, ain't he? Very well, then; is a preacher going to deceive a steamboat clerk? is he going to deceive a ship clerk?—so as to get them to let Miss Mary Jane go aboard? Now you know he ain't. What will he do, then? Why, he'll say, 'It's a great pity, but my church matters has got to get along the best way they can; for my niece has been exposed to the dreadful pluribus-unum mumps, and so it's my bounden duty to set down here and wait the three months it takes to show on her if she's got it.' But never mind, if you think it's best to tell your uncle Harvey—” “Shucks, and stay fooling around here when we could all be having good times in England whilst we was waiting to find out whether Mary Jane's got it or not? Why, you talk like a muggins.” “Well, anyway, maybe you'd better tell some of the neighbors.” “Listen at that, now. You do beat all for natural stupidness. Can't you see that they'd go and tell? Ther' ain't no way but just to not tell anybody at all.” “Well, maybe you're right—yes, I judge you are right.” “But I reckon we ought to tell Uncle Harvey she's gone out a while, anyway, so he won't be uneasy about her?” “Yes, Miss Mary Jane she wanted you to do that. She says, 'Tell them to give Uncle Harvey and William my love and a kiss, and say I've run over the river to see Mr.'—Mr.—what is the name of that rich family your uncle Peter used to think so much of?—I mean the one that—” “Why, you must mean the Apthorps, ain't it?” “Of course; bother them kind of names, a body can't ever seem to remember them, half the time, somehow. Yes, she said, say she has run over for to ask the Apthorps to be sure and come to the auction and buy this house, because she allowed her uncle Peter would ruther they had it than anybody else; and she's going to stick to them till they say they'll come, and then, if she ain't too tired, she's coming home; and if she is, she'll be home in the morning anyway. She said, don't say nothing about the Proctors, but only about the Apthorps—which 'll be perfectly true, because she is going there to speak about their buying the house; I know it, because she told me so herself.” “All right,” they said, and cleared out to lay for their uncles, and give them the love and the kisses, and tell them the message. Everything was all right now. The girls wouldn't say nothing because they wanted to go to England; and the king and the duke would ruther Mary Jane was off working for the auction than around in reach of Doctor Robinson. I felt very good; I judged I had done it pretty neat—I reckoned Tom Sawyer couldn't a done it no neater himself. Of course he would a throwed more style into it, but I can't do that very handy, not being brung up to it. Well, they held the auction in the public square, along towards the end of the afternoon, and it strung along, and strung along, and the old man he was on hand and looking his level pisonest, up there longside of the auctioneer, and chipping in a little Scripture now and then, or a little goody-goody saying of some kind, and the duke he was around goo-gooing for sympathy all he knowed how, and just spreading himself generly. But by and by the thing dragged through, and everything was sold—everything but a little old trifling lot in the graveyard. So they'd got to work that off—I never see such a girafft as the king was for wanting to swallow everything. Well, whilst they was at it a steamboat landed, and in about two minutes up comes a crowd a-whooping and yelling and laughing and carrying on, and singing out: “Here's your opposition line! here's your two sets o' heirs to old Peter Wilks—and you pays your money and you takes your choice!” CHAPTER XXIX. THEY was fetching a very nice-looking old gentleman along, and a nice-looking younger one, with his right arm in a sling. And, my souls, how the people yelled and laughed, and kept it up. But I didn't see no joke about it, and I judged it would strain the duke and the king some to see any. I reckoned they'd turn pale. But no, nary a pale did they turn. The duke he never let on he suspicioned what was up, but just went a goo-gooing around, happy and satisfied, like a jug that's googling out buttermilk; and as for the king, he just gazed and gazed down sorrowful on them new-comers like it give him the stomach-ache in his very heart to think there could be such frauds and rascals in the world. Oh, he done it admirable. Lots of the principal people gethered around the king, to let him see they was on his side. That old gentleman that had just come looked all puzzled to death. Pretty soon he begun to speak, and I see straight off he pronounced like an Englishman—not the king's way, though the king's was pretty good for an imitation. I can't give the old gent's words, nor I can't imitate him; but he turned around to the crowd, and says, about like this: “This is a surprise to me which I wasn't looking for; and I'll acknowledge, candid and frank, I ain't very well fixed to meet it and answer it; for my brother and me has had misfortunes; he's broke his arm, and our baggage got put off at a town above here last night in the night by a mistake. I am Peter Wilks' brother Harvey, and this is his brother William, which can't hear nor speak—and can't even make signs to amount to much, now't he's only got one hand to work them with. We are who we say we are; and in a day or two, when I get the baggage, I can prove it. But up till then I won't say nothing more, but go to the hotel and wait.” So him and the new dummy started off; and the king he laughs, and blethers out: “Broke his arm—very likely, ain't it?—and very convenient, too, for a fraud that's got to make signs, and ain't learnt how. Lost their baggage! That's mighty good!—and mighty ingenious—under the circumstances!” So he laughed again; and so did everybody else, except three or four, or maybe half a dozen. One of these was that doctor; another one was a sharp-looking gentleman, with a carpet-bag of the old-fashioned kind made out of carpet-stuff, that had just come off of the steamboat and was talking to him in a low voice, and glancing towards the king now and then and nodding their heads—it was Levi Bell, the lawyer that was gone up to Louisville; and another one was a big rough husky that come along and listened to all the old gentleman said, and was listening to the king now. And when the king got done this husky up and says: “Say, looky here; if you are Harvey Wilks, when'd you come to this town?” “The day before the funeral, friend,” says the king. “But what time o' day?” “In the evenin'—'bout an hour er two before sundown.” “How'd you come?” “I come down on the Susan Powell from Cincinnati.” “Well, then, how'd you come to be up at the Pint in the mornin'—in a canoe?” “I warn't up at the Pint in the mornin'.” “It's a lie.” Several of them jumped for him and begged him not to talk that way to an old man and a preacher. “Preacher be hanged, he's a fraud and a liar. He was up at the Pint that mornin'. I live up there, don't I? Well, I was up there, and he was up there. I see him there. He come in a canoe, along with Tim Collins and a boy.” The doctor he up and says: “Would you know the boy again if you was to see him, Hines?” “I reckon I would, but I don't know. Why, yonder he is, now. I know him perfectly easy.” It was me he pointed at. The doctor says: “Neighbors, I don't know whether the new couple is frauds or not; but if these two ain't frauds, I am an idiot, that's all. I think it's our duty to see that they don't get away from here till we've looked into this thing. Come along, Hines; come along, the rest of you. We'll take these fellows to the tavern and affront them with t'other couple, and I reckon we'll find out something before we get through.” It was nuts for the crowd, though maybe not for the king's friends; so we all started. It was about sundown. The doctor he led me along by the hand, and was plenty kind enough, but he never let go my hand. We all got in a big room in the hotel, and lit up some candles, and fetched in the new couple. First, the doctor says: “I don't wish to be too hard on these two men, but I think they're frauds, and they may have complices that we don't know nothing about. If they have, won't the complices get away with that bag of gold Peter Wilks left? It ain't unlikely. If these men ain't frauds, they won't object to sending for that money and letting us keep it till they prove they're all right—ain't that so?” Everybody agreed to that. So I judged they had our gang in a pretty tight place right at the outstart. But the king he only looked sorrowful, and says: “Gentlemen, I wish the money was there, for I ain't got no disposition to throw anything in the way of a fair, open, out-and-out investigation o' this misable business; but, alas, the money ain't there; you k'n send and see, if you want to.” “Where is it, then?” “Well, when my niece give it to me to keep for her I took and hid it inside o' the straw tick o' my bed, not wishin' to bank it for the few days we'd be here, and considerin' the bed a safe place, we not bein' used to niggers, and suppos'n' 'em honest, like servants in England. The niggers stole it the very next mornin' after I had went down stairs; and when I sold 'em I hadn't missed the money yit, so they got clean away with it. My servant here k'n tell you 'bout it, gentlemen.” The doctor and several said “Shucks!” and I see nobody didn't altogether believe him. One man asked me if I see the niggers steal it. I said no, but I see them sneaking out of the room and hustling away, and I never thought nothing, only I reckoned they was afraid they had waked up my master and was trying to get away before he made trouble with them. That was all they asked me. Then the doctor whirls on me and says: “Are you English, too?” I says yes; and him and some others laughed, and said, “Stuff!” Well, then they sailed in on the general investigation, and there we had it, up and down, hour in, hour out, and nobody never said a word about supper, nor ever seemed to think about it—and so they kept it up, and kept it up; and it was the worst mixed-up thing you ever see. They made the king tell his yarn, and they made the old gentleman tell his'n; and anybody but a lot of prejudiced chuckleheads would a seen that the old gentleman was spinning truth and t'other one lies. And by and by they had me up to tell what I knowed. The king he give me a left-handed look out of the corner of his eye, and so I knowed enough to talk on the right side. I begun to tell about Sheffield, and how we lived there, and all about the English Wilkses, and so on; but I didn't get pretty fur till the doctor begun to laugh; and Levi Bell, the lawyer, says: “Set down, my boy; I wouldn't strain myself if I was you. I reckon you ain't used to lying, it don't seem to come handy; what you want is practice. You do it pretty awkward.” I didn't care nothing for the compliment, but I was glad to be let off, anyway. The doctor he started to say something, and turns and says: “If you'd been in town at first, Levi Bell—” The king broke in and reached out his hand, and says: “Why, is this my poor dead brother's old friend that he's wrote so often about?” The lawyer and him shook hands, and the lawyer smiled and looked pleased, and they talked right along awhile, and then got to one side and talked low; and at last the lawyer speaks up and says: “That 'll fix it. I'll take the order and send it, along with your brother's, and then they'll know it's all right.” So they got some paper and a pen, and the king he set down and twisted his head to one side, and chawed his tongue, and scrawled off something; and then they give the pen to the duke—and then for the first time the duke looked sick. But he took the pen and wrote. So then the lawyer turns to the new old gentleman and says: “You and your brother please write a line or two and sign your names.” The old gentleman wrote, but nobody couldn't read it. The lawyer looked powerful astonished, and says: “Well, it beats me”—and snaked a lot of old letters out of his pocket, and examined them, and then examined the old man's writing, and then them again; and then says: "These old letters is from Harvey Wilks; and here's these two handwritings, and anybody can see they didn't write them” (the king and the duke looked sold and foolish, I tell you, to see how the lawyer had took them in), “and here's this old gentleman's hand writing, and anybody can tell, easy enough, he didn't write them—fact is, the scratches he makes ain't properly writing at all. Now, here's some letters from—” The new old gentleman says: “If you please, let me explain. Nobody can read my hand but my brother there—so he copies for me. It's his hand you've got there, not mine.” “Well!” says the lawyer, “this is a state of things. I've got some of William's letters, too; so if you'll get him to write a line or so we can com—” “He can't write with his left hand,” says the old gentleman. "If he could use his right hand, you would see that he wrote his own letters and mine too. Look at both, please—they're by the same hand.” The lawyer done it, and says: “I believe it's so—and if it ain't so, there's a heap stronger resemblance than I'd noticed before, anyway. Well, well, well! I thought we was right on the track of a solution, but it's gone to grass, partly. But anyway, one thing is proved—these two ain't either of 'em Wilkses”—and he wagged his head towards the king and the duke. Well, what do you think? That muleheaded old fool wouldn't give in then! Indeed he wouldn't. Said it warn't no fair test. Said his brother William was the cussedest joker in the world, and hadn't tried to write—he see William was going to play one of his jokes the minute he put the pen to paper. And so he warmed up and went warbling and warbling right along till he was actuly beginning to believe what he was saying himself; but pretty soon the new gentleman broke in, and says: “I've thought of something. Is there anybody here that helped to lay out my br—helped to lay out the late Peter Wilks for burying?” “Yes,” says somebody, “me and Ab Turner done it. We're both here.” Then the old man turns towards the king, and says: “Perhaps this gentleman can tell me what was tattooed on his breast?” Blamed if the king didn't have to brace up mighty quick, or he'd a squshed down like a bluff bank that the river has cut under, it took him so sudden; and, mind you, it was a thing that was calculated to make most anybody sqush to get fetched such a solid one as that without any notice, because how was he going to know what was tattooed on the man? He whitened a little; he couldn't help it; and it was mighty still in there, and everybody bending a little forwards and gazing at him. Says I to myself, now he'll throw up the sponge—there ain't no more use. Well, did he? A body can't hardly believe it, but he didn't. I reckon he thought he'd keep the thing up till he tired them people out, so they'd thin out, and him and the duke could break loose and get away. Anyway, he set there, and pretty soon he begun to smile, and says: “Mf! It's a very tough question, ain't it! yes, sir, I k'n tell you what's tattooed on his breast. It's jest a small, thin, blue arrow—that's what it is; and if you don't look clost, you can't see it. now what do you say—hey?” Well, I never see anything like that old blister for clean out-and-out cheek. The new old gentleman turns brisk towards Ab Turner and his pard, and his eye lights up like he judged he'd got the king this time, and says: “There—you've heard what he said! Was there any such mark on Peter Wilks' breast?” Both of them spoke up and says: “We didn't see no such mark.” “Good!” says the old gentleman. "Now, what you did see on his breast was a small dim P, and a B (which is an initial he dropped when he was young), and a W, with dashes between them, so: P—B—W”—and he marked them that way on a piece of paper. "Come, ain't that what you saw?” Both of them spoke up again, and says: “No, we didn't. We never seen any marks at all.” Well, everybody was in a state of mind now, and they sings out: “The whole bilin' of 'm 's frauds! Le's duck 'em! le's drown 'em! le's ride 'em on a rail!” and everybody was whooping at once, and there was a rattling powwow. But the lawyer he jumps on the table and yells, and says: “Gentlemen—gentlemen! Hear me just a word—just a single word—if you please! There's one way yet—let's go and dig up the corpse and look.” That took them. “Hooray!” they all shouted, and was starting right off; but the lawyer and the doctor sung out: “Hold on, hold on! Collar all these four men and the boy, and fetch them along, too!” “We'll do it!” they all shouted; “and if we don't find them marks we'll lynch the whole gang!” I was scared, now, I tell you. But there warn't no getting away, you know. They gripped us all, and marched us right along, straight for the graveyard, which was a mile and a half down the river, and the whole town at our heels, for we made noise enough, and it was only nine in the evening. As we went by our house I wished I hadn't sent Mary Jane out of town; because now if I could tip her the wink she'd light out and save me, and blow on our dead-beats. Well, we swarmed along down the river road, just carrying on like wildcats; and to make it more scary the sky was darking up, and the lightning beginning to wink and flitter, and the wind to shiver amongst the leaves. This was the most awful trouble and most dangersome I ever was in; and I was kinder stunned; everything was going so different from what I had allowed for; stead of being fixed so I could take my own time if I wanted to, and see all the fun, and have Mary Jane at my back to save me and set me free when the close-fit come, here was nothing in the world betwixt me and sudden death but just them tattoo-marks. If they didn't find them— I couldn't bear to think about it; and yet, somehow, I couldn't think about nothing else. It got darker and darker, and it was a beautiful time to give the crowd the slip; but that big husky had me by the wrist—Hines—and a body might as well try to give Goliar the slip. He dragged me right along, he was so excited, and I had to run to keep up. When they got there they swarmed into the graveyard and washed over it like an overflow. And when they got to the grave they found they had about a hundred times as many shovels as they wanted, but nobody hadn't thought to fetch a lantern. But they sailed into digging anyway by the flicker of the lightning, and sent a man to the nearest house, a half a mile off, to borrow one. So they dug and dug like everything; and it got awful dark, and the rain started, and the wind swished and swushed along, and the lightning come brisker and brisker, and the thunder boomed; but them people never took no notice of it, they was so full of this business; and one minute you could see everything and every face in that big crowd, and the shovelfuls of dirt sailing up out of the grave, and the next second the dark wiped it all out, and you couldn't see nothing at all. At last they got out the coffin and begun to unscrew the lid, and then such another crowding and shouldering and shoving as there was, to scrouge in and get a sight, you never see; and in the dark, that way, it was awful. Hines he hurt my wrist dreadful pulling and tugging so, and I reckon he clean forgot I was in the world, he was so excited and panting. All of a sudden the lightning let go a perfect sluice of white glare, and somebody sings out: “By the living jingo, here's the bag of gold on his breast!” Hines let out a whoop, like everybody else, and dropped my wrist and give a big surge to bust his way in and get a look, and the way I lit out and shinned for the road in the dark there ain't nobody can tell. I had the road all to myself, and I fairly flew—leastways, I had it all to myself except the solid dark, and the now-and-then glares, and the buzzing of the rain, and the thrashing of the wind, and the splitting of the thunder; and sure as you are born I did clip it along! When I struck the town I see there warn't nobody out in the storm, so I never hunted for no back streets, but humped it straight through the main one; and when I begun to get towards our house I aimed my eye and set it. No light there; the house all dark—which made me feel sorry and disappointed, I didn't know why. But at last, just as I was sailing by, flash comes the light in Mary Jane's window! and my heart swelled up sudden, like to bust; and the same second the house and all was behind me in the dark, and wasn't ever going to be before me no more in this world. She was the best girl I ever see, and had the most sand. The minute I was far enough above the town to see I could make the towhead, I begun to look sharp for a boat to borrow, and the first time the lightning showed me one that wasn't chained I snatched it and shoved. It was a canoe, and warn't fastened with nothing but a rope. The towhead was a rattling big distance off, away out there in the middle of the river, but I didn't lose no time; and when I struck the raft at last I was so fagged I would a just laid down to blow and gasp if I could afforded it. But I didn't. As I sprung aboard I sung out: “Out with you, Jim, and set her loose! Glory be to goodness, we're shut of them!” Jim lit out, and was a-coming for me with both arms spread, he was so full of joy; but when I glimpsed him in the lightning my heart shot up in my mouth and I went overboard backwards; for I forgot he was old King Lear and a drownded A-rab all in one, and it most scared the livers and lights out of me. But Jim fished me out, and was going to hug me and bless me, and so on, he was so glad I was back and we was shut of the king and the duke, but I says: “Not now; have it for breakfast, have it for breakfast! Cut loose and let her slide!” So in two seconds away we went a-sliding down the river, and it did seem so good to be free again and all by ourselves on the big river, and nobody to bother us. I had to skip around a bit, and jump up and crack my heels a few times—I couldn't help it; but about the third crack I noticed a sound that I knowed mighty well, and held my breath and listened and waited; and sure enough, when the next flash busted out over the water, here they come!—and just a-laying to their oars and making their skiff hum! It was the king and the duke. So I wilted right down on to the planks then, and give up; and it was all I could do to keep from crying. CHAPTER XXX. WHEN they got aboard the king went for me, and shook me by the collar, and says: “Tryin' to give us the slip, was ye, you pup! Tired of our company, hey?” I says: “No, your majesty, we warn't—please don't, your majesty!” “Quick, then, and tell us what was your idea, or I'll shake the insides out o' you!” “Honest, I'll tell you everything just as it happened, your majesty. The man that had a-holt of me was very good to me, and kept saying he had a boy about as big as me that died last year, and he was sorry to see a boy in such a dangerous fix; and when they was all took by surprise by finding the gold, and made a rush for the coffin, he lets go of me and whispers, 'Heel it now, or they'll hang ye, sure!' and I lit out. It didn't seem no good for me to stay—I couldn't do nothing, and I didn't want to be hung if I could get away. So I never stopped running till I found the canoe; and when I got here I told Jim to hurry, or they'd catch me and hang me yet, and said I was afeard you and the duke wasn't alive now, and I was awful sorry, and so was Jim, and was awful glad when we see you coming; you may ask Jim if I didn't.” Jim said it was so; and the king told him to shut up, and said, “Oh, yes, it's mighty likely!” and shook me up again, and said he reckoned he'd drownd me. But the duke says: “Leggo the boy, you old idiot! Would you a done any different? Did you inquire around for him when you got loose? I don't remember it.” So the king let go of me, and begun to cuss that town and everybody in it. But the duke says: “You better a blame' sight give yourself a good cussing, for you're the one that's entitled to it most. You hain't done a thing from the start that had any sense in it, except coming out so cool and cheeky with that imaginary blue-arrow mark. That was bright—it was right down bully; and it was the thing that saved us. For if it hadn't been for that they'd a jailed us till them Englishmen's baggage come—and then—the penitentiary, you bet! But that trick took 'em to the graveyard, and the gold done us a still bigger kindness; for if the excited fools hadn't let go all holts and made that rush to get a look we'd a slept in our cravats to-night—cravats warranted to wear, too—longer than we'd need 'em.” They was still a minute—thinking; then the king says, kind of absent-minded like: “Mf! And we reckoned the niggers stole it!” That made me squirm! “Yes,” says the duke, kinder slow and deliberate and sarcastic, “we did.” After about a half a minute the king drawls out: “Leastways, I did.” The duke says, the same way: “On the contrary, I did.” The king kind of ruffles up, and says: “Looky here, Bilgewater, what'r you referrin' to?” The duke says, pretty brisk: “When it comes to that, maybe you'll let me ask, what was you referring to?” “Shucks!” says the king, very sarcastic; “but I don't know—maybe you was asleep, and didn't know what you was about.” The duke bristles up now, and says: “Oh, let up on this cussed nonsense; do you take me for a blame' fool? Don't you reckon I know who hid that money in that coffin?” “Yes, sir! I know you do know, because you done it yourself!” “It's a lie!”—and the duke went for him. The king sings out: “Take y'r hands off!—leggo my throat!—I take it all back!” The duke says: “Well, you just own up, first, that you did hide that money there, intending to give me the slip one of these days, and come back and dig it up, and have it all to yourself.” “Wait jest a minute, duke—answer me this one question, honest and fair; if you didn't put the money there, say it, and I'll b'lieve you, and take back everything I said.” “You old scoundrel, I didn't, and you know I didn't. There, now!” “Well, then, I b'lieve you. But answer me only jest this one more—now don't git mad; didn't you have it in your mind to hook the money and hide it?” The duke never said nothing for a little bit; then he says: “Well, I don't care if I did, I didn't do it, anyway. But you not only had it in mind to do it, but you done it.” “I wisht I never die if I done it, duke, and that's honest. I won't say I warn't goin' to do it, because I was; but you—I mean somebody—got in ahead o' me.” “It's a lie! You done it, and you got to say you done it, or—” The king began to gurgle, and then he gasps out: “'Nough!—I own up!” I was very glad to hear him say that; it made me feel much more easier than what I was feeling before. So the duke took his hands off and says: “If you ever deny it again I'll drown you. It's well for you to set there and blubber like a baby—it's fitten for you, after the way you've acted. I never see such an old ostrich for wanting to gobble everything—and I a-trusting you all the time, like you was my own father. You ought to been ashamed of yourself to stand by and hear it saddled on to a lot of poor niggers, and you never say a word for 'em. It makes me feel ridiculous to think I was soft enough to believe that rubbage. Cuss you, I can see now why you was so anxious to make up the deffisit—you wanted to get what money I'd got out of the Nonesuch and one thing or another, and scoop it all!” The king says, timid, and still a-snuffling: “Why, duke, it was you that said make up the deffisit; it warn't me.” “Dry up! I don't want to hear no more out of you!” says the duke. "And now you see what you GOT by it. They've got all their own money back, and all of ourn but a shekel or two besides. G'long to bed, and don't you deffersit me no more deffersits, long 's you live!” So the king sneaked into the wigwam and took to his bottle for comfort, and before long the duke tackled HIS bottle; and so in about a half an hour they was as thick as thieves again, and the tighter they got the lovinger they got, and went off a-snoring in each other's arms. They both got powerful mellow, but I noticed the king didn't get mellow enough to forget to remember to not deny about hiding the money-bag again. That made me feel easy and satisfied. Of course when they got to snoring we had a long gabble, and I told Jim everything. CHAPTER XXXI. WE dasn't stop again at any town for days and days; kept right along down the river. We was down south in the warm weather now, and a mighty long ways from home. We begun to come to trees with Spanish moss on them, hanging down from the limbs like long, gray beards. It was the first I ever see it growing, and it made the woods look solemn and dismal. So now the frauds reckoned they was out of danger, and they begun to work the villages again. First they done a lecture on temperance; but they didn't make enough for them both to get drunk on. Then in another village they started a dancing-school; but they didn't know no more how to dance than a kangaroo does; so the first prance they made the general public jumped in and pranced them out of town. Another time they tried to go at yellocution; but they didn't yellocute long till the audience got up and give them a solid good cussing, and made them skip out. They tackled missionarying, and mesmerizing, and doctoring, and telling fortunes, and a little of everything; but they couldn't seem to have no luck. So at last they got just about dead broke, and laid around the raft as she floated along, thinking and thinking, and never saying nothing, by the half a day at a time, and dreadful blue and desperate. And at last they took a change and begun to lay their heads together in the wigwam and talk low and confidential two or three hours at a time. Jim and me got uneasy. We didn't like the look of it. We judged they was studying up some kind of worse deviltry than ever. We turned it over and over, and at last we made up our minds they was going to break into somebody's house or store, or was going into the counterfeit-money business, or something. So then we was pretty scared, and made up an agreement that we wouldn't have nothing in the world to do with such actions, and if we ever got the least show we would give them the cold shake and clear out and leave them behind. Well, early one morning we hid the raft in a good, safe place about two mile below a little bit of a shabby village named Pikesville, and the king he went ashore and told us all to stay hid whilst he went up to town and smelt around to see if anybody had got any wind of the Royal Nonesuch there yet. (“House to rob, you mean,” says I to myself; “and when you get through robbing it you'll come back here and wonder what has become of me and Jim and the raft—and you'll have to take it out in wondering.”) And he said if he warn't back by midday the duke and me would know it was all right, and we was to come along. So we stayed where we was. The duke he fretted and sweated around, and was in a mighty sour way. He scolded us for everything, and we couldn't seem to do nothing right; he found fault with every little thing. Something was a-brewing, sure. I was good and glad when midday come and no king; we could have a change, anyway—and maybe a chance for the change on top of it. So me and the duke went up to the village, and hunted around there for the king, and by and by we found him in the back room of a little low doggery, very tight, and a lot of loafers bullyragging him for sport, and he a-cussing and a-threatening with all his might, and so tight he couldn't walk, and couldn't do nothing to them. The duke he begun to abuse him for an old fool, and the king begun to sass back, and the minute they was fairly at it I lit out and shook the reefs out of my hind legs, and spun down the river road like a deer, for I see our chance; and I made up my mind that it would be a long day before they ever see me and Jim again. I got down there all out of breath but loaded up with joy, and sung out: “Set her loose, Jim! we're all right now!” But there warn't no answer, and nobody come out of the wigwam. Jim was gone! I set up a shout—and then another—and then another one; and run this way and that in the woods, whooping and screeching; but it warn't no use—old Jim was gone. Then I set down and cried; I couldn't help it. But I couldn't set still long. Pretty soon I went out on the road, trying to think what I better do, and I run across a boy walking, and asked him if he'd seen a strange nigger dressed so and so, and he says: “Yes.” “Whereabouts?” says I. “Down to Silas Phelps' place, two mile below here. He's a runaway nigger, and they've got him. Was you looking for him?” “You bet I ain't! I run across him in the woods about an hour or two ago, and he said if I hollered he'd cut my livers out—and told me to lay down and stay where I was; and I done it. Been there ever since; afeard to come out.” “Well,” he says, “you needn't be afeard no more, becuz they've got him. He run off f'm down South, som'ers.” “It's a good job they got him.” “Well, I reckon! There's two hunderd dollars reward on him. It's like picking up money out'n the road.” “Yes, it is—and I could a had it if I'd been big enough; I see him first. Who nailed him?” “It was an old fellow—a stranger—and he sold out his chance in him for forty dollars, becuz he's got to go up the river and can't wait. Think o' that, now! You bet I'd wait, if it was seven year.” “That's me, every time,” says I. "But maybe his chance ain't worth no more than that, if he'll sell it so cheap. Maybe there's something ain't straight about it.” “But it is, though—straight as a string. I see the handbill myself. It tells all about him, to a dot—paints him like a picture, and tells the plantation he's frum, below Newrleans. No-sirree-bob, they ain't no trouble 'bout that speculation, you bet you. Say, gimme a chaw tobacker, won't ye?” I didn't have none, so he left. I went to the raft, and set down in the wigwam to think. But I couldn't come to nothing. I thought till I wore my head sore, but I couldn't see no way out of the trouble. After all this long journey, and after all we'd done for them scoundrels, here it was all come to nothing, everything all busted up and ruined, because they could have the heart to serve Jim such a trick as that, and make him a slave again all his life, and amongst strangers, too, for forty dirty dollars. Once I said to myself it would be a thousand times better for Jim to be a slave at home where his family was, as long as he'd got to be a slave, and so I'd better write a letter to Tom Sawyer and tell him to tell Miss Watson where he was. But I soon give up that notion for two things: she'd be mad and disgusted at his rascality and ungratefulness for leaving her, and so she'd sell him straight down the river again; and if she didn't, everybody naturally despises an ungrateful nigger, and they'd make Jim feel it all the time, and so he'd feel ornery and disgraced. And then think of me! It would get all around that Huck Finn helped a nigger to get his freedom; and if I was ever to see anybody from that town again I'd be ready to get down and lick his boots for shame. That's just the way: a person does a low-down thing, and then he don't want to take no consequences of it. Thinks as long as he can hide it, it ain't no disgrace. That was my fix exactly. The more I studied about this the more my conscience went to grinding me, and the more wicked and low-down and ornery I got to feeling. And at last, when it hit me all of a sudden that here was the plain hand of Providence slapping me in the face and letting me know my wickedness was being watched all the time from up there in heaven, whilst I was stealing a poor old woman's nigger that hadn't ever done me no harm, and now was showing me there's One that's always on the lookout, and ain't a-going to allow no such miserable doings to go only just so fur and no further, I most dropped in my tracks I was so scared. Well, I tried the best I could to kinder soften it up somehow for myself by saying I was brung up wicked, and so I warn't so much to blame; but something inside of me kept saying, “There was the Sunday-school, you could a gone to it; and if you'd a done it they'd a learnt you there that people that acts as I'd been acting about that nigger goes to everlasting fire.” It made me shiver. And I about made up my mind to pray, and see if I couldn't try to quit being the kind of a boy I was and be better. So I kneeled down. But the words wouldn't come. Why wouldn't they? It warn't no use to try and hide it from Him. Nor from me, neither. I knowed very well why they wouldn't come. It was because my heart warn't right; it was because I warn't square; it was because I was playing double. I was letting on to give up sin, but away inside of me I was holding on to the biggest one of all. I was trying to make my mouth say I would do the right thing and the clean thing, and go and write to that nigger's owner and tell where he was; but deep down in me I knowed it was a lie, and He knowed it. You can't pray a lie—I found that out. So I was full of trouble, full as I could be; and didn't know what to do. At last I had an idea; and I says, I'll go and write the letter—and then see if I can pray. Why, it was astonishing, the way I felt as light as a feather right straight off, and my troubles all gone. So I got a piece of paper and a pencil, all glad and excited, and set down and wrote: Miss Watson, your runaway nigger Jim is down here two mile below Pikesville, and Mr. Phelps has got him and he will give him up for the reward if you send. Huck Finn. I felt good and all washed clean of sin for the first time I had ever felt so in my life, and I knowed I could pray now. But I didn't do it straight off, but laid the paper down and set there thinking—thinking how good it was all this happened so, and how near I come to being lost and going to hell. And went on thinking. And got to thinking over our trip down the river; and I see Jim before me all the time: in the day and in the night-time, sometimes moonlight, sometimes storms, and we a-floating along, talking and singing and laughing. But somehow I couldn't seem to strike no places to harden me against him, but only the other kind. I'd see him standing my watch on top of his'n, 'stead of calling me, so I could go on sleeping; and see him how glad he was when I come back out of the fog; and when I come to him again in the swamp, up there where the feud was; and such-like times; and would always call me honey, and pet me and do everything he could think of for me, and how good he always was; and at last I struck the time I saved him by telling the men we had small-pox aboard, and he was so grateful, and said I was the best friend old Jim ever had in the world, and the only one he's got now; and then I happened to look around and see that paper. It was a close place. I took it up, and held it in my hand. I was a-trembling, because I'd got to decide, forever, betwixt two things, and I knowed it. I studied a minute, sort of holding my breath, and then says to myself: “All right, then, I'll go to hell”—and tore it up. It was awful thoughts and awful words, but they was said. And I let them stay said; and never thought no more about reforming. I shoved the whole thing out of my head, and said I would take up wickedness again, which was in my line, being brung up to it, and the other warn't. And for a starter I would go to work and steal Jim out of slavery again; and if I could think up anything worse, I would do that, too; because as long as I was in, and in for good, I might as well go the whole hog. Then I set to thinking over how to get at it, and turned over some considerable many ways in my mind; and at last fixed up a plan that suited me. So then I took the bearings of a woody island that was down the river a piece, and as soon as it was fairly dark I crept out with my raft and went for it, and hid it there, and then turned in. I slept the night through, and got up before it was light, and had my breakfast, and put on my store clothes, and tied up some others and one thing or another in a bundle, and took the canoe and cleared for shore. I landed below where I judged was Phelps's place, and hid my bundle in the woods, and then filled up the canoe with water, and loaded rocks into her and sunk her where I could find her again when I wanted her, about a quarter of a mile below a little steam sawmill that was on the bank. Then I struck up the road, and when I passed the mill I see a sign on it, “Phelps's Sawmill,” and when I come to the farm-houses, two or three hundred yards further along, I kept my eyes peeled, but didn't see nobody around, though it was good daylight now. But I didn't mind, because I didn't want to see nobody just yet—I only wanted to get the lay of the land. According to my plan, I was going to turn up there from the village, not from below. So I just took a look, and shoved along, straight for town. Well, the very first man I see when I got there was the duke. He was sticking up a bill for the Royal Nonesuch—three-night performance—like that other time. They had the cheek, them frauds! I was right on him before I could shirk. He looked astonished, and says: “Hel-lo! Where'd you come from?” Then he says, kind of glad and eager, “Where's the raft?—got her in a good place?” I says: “Why, that's just what I was going to ask your grace.” Then he didn't look so joyful, and says: “What was your idea for asking me?” he says. “Well,” I says, “when I see the king in that doggery yesterday I says to myself, we can't get him home for hours, till he's soberer; so I went a-loafing around town to put in the time and wait. A man up and offered me ten cents to help him pull a skiff over the river and back to fetch a sheep, and so I went along; but when we was dragging him to the boat, and the man left me a-holt of the rope and went behind him to shove him along, he was too strong for me and jerked loose and run, and we after him. We didn't have no dog, and so we had to chase him all over the country till we tired him out. We never got him till dark; then we fetched him over, and I started down for the raft. When I got there and see it was gone, I says to myself, 'They've got into trouble and had to leave; and they've took my nigger, which is the only nigger I've got in the world, and now I'm in a strange country, and ain't got no property no more, nor nothing, and no way to make my living;' so I set down and cried. I slept in the woods all night. But what did become of the raft, then?—and Jim—poor Jim!” “Blamed if I know—that is, what's become of the raft. That old fool had made a trade and got forty dollars, and when we found him in the doggery the loafers had matched half-dollars with him and got every cent but what he'd spent for whisky; and when I got him home late last night and found the raft gone, we said, 'That little rascal has stole our raft and shook us, and run off down the river.'” “I wouldn't shake my nigger, would I?—the only nigger I had in the world, and the only property.” “We never thought of that. Fact is, I reckon we'd come to consider him our nigger; yes, we did consider him so—goodness knows we had trouble enough for him. So when we see the raft was gone and we flat broke, there warn't anything for it but to try the Royal Nonesuch another shake. And I've pegged along ever since, dry as a powder-horn. Where's that ten cents? Give it here.” I had considerable money, so I give him ten cents, but begged him to spend it for something to eat, and give me some, because it was all the money I had, and I hadn't had nothing to eat since yesterday. He never said nothing. The next minute he whirls on me and says: “Do you reckon that nigger would blow on us? We'd skin him if he done that!” “How can he blow? Hain't he run off?” “No! That old fool sold him, and never divided with me, and the money's gone.” “Sold him?” I says, and begun to cry; “why, he was my nigger, and that was my money. Where is he?—I want my nigger.” “Well, you can't get your nigger, that's all—so dry up your blubbering. Looky here—do you think you'd venture to blow on us? Blamed if I think I'd trust you. Why, if you was to blow on us—” He stopped, but I never see the duke look so ugly out of his eyes before. I went on a-whimpering, and says: “I don't want to blow on nobody; and I ain't got no time to blow, nohow. I got to turn out and find my nigger.” He looked kinder bothered, and stood there with his bills fluttering on his arm, thinking, and wrinkling up his forehead. At last he says: “I'll tell you something. We got to be here three days. If you'll promise you won't blow, and won't let the nigger blow, I'll tell you where to find him.” So I promised, and he says: “A farmer by the name of Silas Ph—” and then he stopped. You see, he started to tell me the truth; but when he stopped that way, and begun to study and think again, I reckoned he was changing his mind. And so he was. He wouldn't trust me; he wanted to make sure of having me out of the way the whole three days. So pretty soon he says: “The man that bought him is named Abram Foster—Abram G. Foster—and he lives forty mile back here in the country, on the road to Lafayette.” “All right,” I says, “I can walk it in three days. And I'll start this very afternoon.” “No you wont, you'll start now; and don't you lose any time about it, neither, nor do any gabbling by the way. Just keep a tight tongue in your head and move right along, and then you won't get into trouble with us, d'ye hear?” That was the order I wanted, and that was the one I played for. I wanted to be left free to work my plans. “So clear out,” he says; “and you can tell Mr. Foster whatever you want to. Maybe you can get him to believe that Jim is your nigger—some idiots don't require documents—leastways I've heard there's such down South here. And when you tell him the handbill and the reward's bogus, maybe he'll believe you when you explain to him what the idea was for getting 'em out. Go 'long now, and tell him anything you want to; but mind you don't work your jaw any between here and there.” So I left, and struck for the back country. I didn't look around, but I kinder felt like he was watching me. But I knowed I could tire him out at that. I went straight out in the country as much as a mile before I stopped; then I doubled back through the woods towards Phelps'. I reckoned I better start in on my plan straight off without fooling around, because I wanted to stop Jim's mouth till these fellows could get away. I didn't want no trouble with their kind. I'd seen all I wanted to of them, and wanted to get entirely shut of them. CHAPTER XXXII. WHEN I got there it was all still and Sunday-like, and hot and sunshiny; the hands was gone to the fields; and there was them kind of faint dronings of bugs and flies in the air that makes it seem so lonesome and like everybody's dead and gone; and if a breeze fans along and quivers the leaves it makes you feel mournful, because you feel like it's spirits whispering—spirits that's been dead ever so many years—and you always think they're talking about you. As a general thing it makes a body wish he was dead, too, and done with it all. Phelps' was one of these little one-horse cotton plantations, and they all look alike. A rail fence round a two-acre yard; a stile made out of logs sawed off and up-ended in steps, like barrels of a different length, to climb over the fence with, and for the women to stand on when they are going to jump on to a horse; some sickly grass-patches in the big yard, but mostly it was bare and smooth, like an old hat with the nap rubbed off; big double log-house for the white folks—hewed logs, with the chinks stopped up with mud or mortar, and these mud-stripes been whitewashed some time or another; round-log kitchen, with a big broad, open but roofed passage joining it to the house; log smoke-house back of the kitchen; three little log nigger-cabins in a row t'other side the smoke-house; one little hut all by itself away down against the back fence, and some outbuildings down a piece the other side; ash-hopper and big kettle to bile soap in by the little hut; bench by the kitchen door, with bucket of water and a gourd; hound asleep there in the sun; more hounds asleep round about; about three shade trees away off in a corner; some currant bushes and gooseberry bushes in one place by the fence; outside of the fence a garden and a watermelon patch; then the cotton fields begins, and after the fields the woods. I went around and clumb over the back stile by the ash-hopper, and started for the kitchen. When I got a little ways I heard the dim hum of a spinning-wheel wailing along up and sinking along down again; and then I knowed for certain I wished I was dead—for that is the lonesomest sound in the whole world. I went right along, not fixing up any particular plan, but just trusting to Providence to put the right words in my mouth when the time come; for I'd noticed that Providence always did put the right words in my mouth if I left it alone. When I got half-way, first one hound and then another got up and went for me, and of course I stopped and faced them, and kept still. And such another powwow as they made! In a quarter of a minute I was a kind of a hub of a wheel, as you may say—spokes made out of dogs—circle of fifteen of them packed together around me, with their necks and noses stretched up towards me, a-barking and howling; and more a-coming; you could see them sailing over fences and around corners from everywheres. A nigger woman come tearing out of the kitchen with a rolling-pin in her hand, singing out, “Begone you Tige! you Spot! begone sah!” and she fetched first one and then another of them a clip and sent them howling, and then the rest followed; and the next second half of them come back, wagging their tails around me, and making friends with me. There ain't no harm in a hound, nohow. And behind the woman comes a little nigger girl and two little nigger boys without anything on but tow-linen shirts, and they hung on to their mother's gown, and peeped out from behind her at me, bashful, the way they always do. And here comes the white woman running from the house, about forty-five or fifty year old, bareheaded, and her spinning-stick in her hand; and behind her comes her little white children, acting the same way the little niggers was doing. She was smiling all over so she could hardly stand—and says: “It's you, at last!—ain't it?” I out with a “Yes'm” before I thought. She grabbed me and hugged me tight; and then gripped me by both hands and shook and shook; and the tears come in her eyes, and run down over; and she couldn't seem to hug and shake enough, and kept saying, “You don't look as much like your mother as I reckoned you would; but law sakes, I don't care for that, I'm so glad to see you! Dear, dear, it does seem like I could eat you up! Children, it's your cousin Tom!—tell him howdy.” But they ducked their heads, and put their fingers in their mouths, and hid behind her. So she run on: “Lize, hurry up and get him a hot breakfast right away—or did you get your breakfast on the boat?” I said I had got it on the boat. So then she started for the house, leading me by the hand, and the children tagging after. When we got there she set me down in a split-bottomed chair, and set herself down on a little low stool in front of me, holding both of my hands, and says: “Now I can have a good look at you; and, laws-a-me, I've been hungry for it a many and a many a time, all these long years, and it's come at last! We been expecting you a couple of days and more. What kep' you?—boat get aground?” “Yes'm—she—” “Don't say yes'm—say Aunt Sally. Where'd she get aground?” I didn't rightly know what to say, because I didn't know whether the boat would be coming up the river or down. But I go a good deal on instinct; and my instinct said she would be coming up—from down towards Orleans. That didn't help me much, though; for I didn't know the names of bars down that way. I see I'd got to invent a bar, or forget the name of the one we got aground on—or—Now I struck an idea, and fetched it out: “It warn't the grounding—that didn't keep us back but a little. We blowed out a cylinder-head.” “Good gracious! anybody hurt?” “No'm. Killed a nigger.” “Well, it's lucky; because sometimes people do get hurt. Two years ago last Christmas your uncle Silas was coming up from Newrleans on the old Lally Rook, and she blowed out a cylinder-head and crippled a man. And I think he died afterwards. He was a Baptist. Your uncle Silas knowed a family in Baton Rouge that knowed his people very well. Yes, I remember now, he did die. Mortification set in, and they had to amputate him. But it didn't save him. Yes, it was mortification—that was it. He turned blue all over, and died in the hope of a glorious resurrection. They say he was a sight to look at. Your uncle's been up to the town every day to fetch you. And he's gone again, not more'n an hour ago; he'll be back any minute now. You must a met him on the road, didn't you?—oldish man, with a—” “No, I didn't see nobody, Aunt Sally. The boat landed just at daylight, and I left my baggage on the wharf-boat and went looking around the town and out a piece in the country, to put in the time and not get here too soon; and so I come down the back way.” “Who'd you give the baggage to?” “Nobody.” “Why, child, it 'll be stole!” “Not where I hid it I reckon it won't,” I says. “How'd you get your breakfast so early on the boat?” It was kinder thin ice, but I says: “The captain see me standing around, and told me I better have something to eat before I went ashore; so he took me in the texas to the officers' lunch, and give me all I wanted.” I was getting so uneasy I couldn't listen good. I had my mind on the children all the time; I wanted to get them out to one side and pump them a little, and find out who I was. But I couldn't get no show, Mrs. Phelps kept it up and run on so. Pretty soon she made the cold chills streak all down my back, because she says: “But here we're a-running on this way, and you hain't told me a word about Sis, nor any of them. Now I'll rest my works a little, and you start up yourn; just tell me everything—tell me all about 'm all every one of 'm; and how they are, and what they're doing, and what they told you to tell me; and every last thing you can think of.” Well, I see I was up a stump—and up it good. Providence had stood by me this fur all right, but I was hard and tight aground now. I see it warn't a bit of use to try to go ahead—I'd got to throw up my hand. So I says to myself, here's another place where I got to resk the truth. I opened my mouth to begin; but she grabbed me and hustled me in behind the bed, and says: “Here he comes! Stick your head down lower—there, that'll do; you can't be seen now. Don't you let on you're here. I'll play a joke on him. Children, don't you say a word.” I see I was in a fix now. But it warn't no use to worry; there warn't nothing to do but just hold still, and try and be ready to stand from under when the lightning struck. I had just one little glimpse of the old gentleman when he come in; then the bed hid him. Mrs. Phelps she jumps for him, and says: “Has he come?” “No,” says her husband. “Good-ness gracious!” she says, “what in the warld can have become of him?” “I can't imagine,” says the old gentleman; “and I must say it makes me dreadful uneasy.” “Uneasy!” she says; “I'm ready to go distracted! He must a come; and you've missed him along the road. I know it's so—something tells me so.” “Why, Sally, I couldn't miss him along the road—you know that.” “But oh, dear, dear, what will Sis say! He must a come! You must a missed him. He—” “Oh, don't distress me any more'n I'm already distressed. I don't know what in the world to make of it. I'm at my wit's end, and I don't mind acknowledging 't I'm right down scared. But there's no hope that he's come; for he couldn't come and me miss him. Sally, it's terrible—just terrible—something's happened to the boat, sure!” “Why, Silas! Look yonder!—up the road!—ain't that somebody coming?” He sprung to the window at the head of the bed, and that give Mrs. Phelps the chance she wanted. She stooped down quick at the foot of the bed and give me a pull, and out I come; and when he turned back from the window there she stood, a-beaming and a-smiling like a house afire, and I standing pretty meek and sweaty alongside. The old gentleman stared, and says: “Why, who's that?” “Who do you reckon 't is?” “I hain't no idea. Who is it?” “It's Tom Sawyer!” By jings, I most slumped through the floor! But there warn't no time to swap knives; the old man grabbed me by the hand and shook, and kept on shaking; and all the time how the woman did dance around and laugh and cry; and then how they both did fire off questions about Sid, and Mary, and the rest of the tribe. But if they was joyful, it warn't nothing to what I was; for it was like being born again, I was so glad to find out who I was. Well, they froze to me for two hours; and at last, when my chin was so tired it couldn't hardly go any more, I had told them more about my family—I mean the Sawyer family—than ever happened to any six Sawyer families. And I explained all about how we blowed out a cylinder-head at the mouth of White River, and it took us three days to fix it. Which was all right, and worked first-rate; because they didn't know but what it would take three days to fix it. If I'd a called it a bolthead it would a done just as well. Now I was feeling pretty comfortable all down one side, and pretty uncomfortable all up the other. Being Tom Sawyer was easy and comfortable, and it stayed easy and comfortable till by and by I hear a steamboat coughing along down the river. Then I says to myself, s'pose Tom Sawyer comes down on that boat? And s'pose he steps in here any minute, and sings out my name before I can throw him a wink to keep quiet? Well, I couldn't have it that way; it wouldn't do at all. I must go up the road and waylay him. So I told the folks I reckoned I would go up to the town and fetch down my baggage. The old gentleman was for going along with me, but I said no, I could drive the horse myself, and I druther he wouldn't take no trouble about me. CHAPTER XXXIII. SO I started for town in the wagon, and when I was half-way I see a wagon coming, and sure enough it was Tom Sawyer, and I stopped and waited till he come along. I says “Hold on!” and it stopped alongside, and his mouth opened up like a trunk, and stayed so; and he swallowed two or three times like a person that's got a dry throat, and then says: “I hain't ever done you no harm. You know that. So, then, what you want to come back and ha'nt me for?” I says: “I hain't come back—I hain't been gone.” When he heard my voice it righted him up some, but he warn't quite satisfied yet. He says: “Don't you play nothing on me, because I wouldn't on you. Honest injun now, you ain't a ghost?” “Honest injun, I ain't,” I says. “Well—I—I—well, that ought to settle it, of course; but I can't somehow seem to understand it no way. Looky here, warn't you ever murdered at all?” “No. I warn't ever murdered at all—I played it on them. You come in here and feel of me if you don't believe me.” So he done it; and it satisfied him; and he was that glad to see me again he didn't know what to do. And he wanted to know all about it right off, because it was a grand adventure, and mysterious, and so it hit him where he lived. But I said, leave it alone till by and by; and told his driver to wait, and we drove off a little piece, and I told him the kind of a fix I was in, and what did he reckon we better do? He said, let him alone a minute, and don't disturb him. So he thought and thought, and pretty soon he says: “It's all right; I've got it. Take my trunk in your wagon, and let on it's your'n; and you turn back and fool along slow, so as to get to the house about the time you ought to; and I'll go towards town a piece, and take a fresh start, and get there a quarter or a half an hour after you; and you needn't let on to know me at first.” I says: “All right; but wait a minute. There's one more thing—a thing that nobody don't know but me. And that is, there's a nigger here that I'm a-trying to steal out of slavery, and his name is Jim—old Miss Watson's Jim.” He says: “What! Why, Jim is—” He stopped and went to studying. I says: “I know what you'll say. You'll say it's dirty, low-down business; but what if it is? I'm low down; and I'm a-going to steal him, and I want you keep mum and not let on. Will you?” His eye lit up, and he says: “I'll help you steal him!” Well, I let go all holts then, like I was shot. It was the most astonishing speech I ever heard—and I'm bound to say Tom Sawyer fell considerable in my estimation. Only I couldn't believe it. Tom Sawyer a nigger-stealer! “Oh, shucks!” I says; “you're joking.” “I ain't joking, either.” “Well, then,” I says, “joking or no joking, if you hear anything said about a runaway nigger, don't forget to remember that you don't know nothing about him, and I don't know nothing about him.” Then we took the trunk and put it in my wagon, and he drove off his way and I drove mine. But of course I forgot all about driving slow on accounts of being glad and full of thinking; so I got home a heap too quick for that length of a trip. The old gentleman was at the door, and he says: “Why, this is wonderful! Whoever would a thought it was in that mare to do it? I wish we'd a timed her. And she hain't sweated a hair—not a hair. It's wonderful. Why, I wouldn't take a hundred dollars for that horse now—I wouldn't, honest; and yet I'd a sold her for fifteen before, and thought 'twas all she was worth.” That's all he said. He was the innocentest, best old soul I ever see. But it warn't surprising; because he warn't only just a farmer, he was a preacher, too, and had a little one-horse log church down back of the plantation, which he built it himself at his own expense, for a church and schoolhouse, and never charged nothing for his preaching, and it was worth it, too. There was plenty other farmer-preachers like that, and done the same way, down South. In about half an hour Tom's wagon drove up to the front stile, and Aunt Sally she see it through the window, because it was only about fifty yards, and says: “Why, there's somebody come! I wonder who 'tis? Why, I do believe it's a stranger. Jimmy” (that's one of the children) “run and tell Lize to put on another plate for dinner.” Everybody made a rush for the front door, because, of course, a stranger don't come every year, and so he lays over the yaller-fever, for interest, when he does come. Tom was over the stile and starting for the house; the wagon was spinning up the road for the village, and we was all bunched in the front door. Tom had his store clothes on, and an audience—and that was always nuts for Tom Sawyer. In them circumstances it warn't no trouble to him to throw in an amount of style that was suitable. He warn't a boy to meeky along up that yard like a sheep; no, he come ca'm and important, like the ram. When he got a-front of us he lifts his hat ever so gracious and dainty, like it was the lid of a box that had butterflies asleep in it and he didn't want to disturb them, and says: “Mr. Archibald Nichols, I presume?” “No, my boy,” says the old gentleman, “I'm sorry to say 't your driver has deceived you; Nichols's place is down a matter of three mile more. Come in, come in.” Tom he took a look back over his shoulder, and says, “Too late—he's out of sight.” “Yes, he's gone, my son, and you must come in and eat your dinner with us; and then we'll hitch up and take you down to Nichols's.” “Oh, I can't make you so much trouble; I couldn't think of it. I'll walk—I don't mind the distance.” “But we won't let you walk—it wouldn't be Southern hospitality to do it. Come right in.” “Oh, do,” says Aunt Sally; “it ain't a bit of trouble to us, not a bit in the world. You must stay. It's a long, dusty three mile, and we can't let you walk. And, besides, I've already told 'em to put on another plate when I see you coming; so you mustn't disappoint us. Come right in and make yourself at home.” So Tom he thanked them very hearty and handsome, and let himself be persuaded, and come in; and when he was in he said he was a stranger from Hicksville, Ohio, and his name was William Thompson—and he made another bow. Well, he run on, and on, and on, making up stuff about Hicksville and everybody in it he could invent, and I getting a little nervious, and wondering how this was going to help me out of my scrape; and at last, still talking along, he reached over and kissed Aunt Sally right on the mouth, and then settled back again in his chair comfortable, and was going on talking; but she jumped up and wiped it off with the back of her hand, and says: “You owdacious puppy!” He looked kind of hurt, and says: “I'm surprised at you, m'am.” “You're s'rp—Why, what do you reckon I am? I've a good notion to take and—Say, what do you mean by kissing me?” He looked kind of humble, and says: “I didn't mean nothing, m'am. I didn't mean no harm. I—I—thought you'd like it.” “Why, you born fool!” She took up the spinning stick, and it looked like it was all she could do to keep from giving him a crack with it. "What made you think I'd like it?” “Well, I don't know. Only, they—they—told me you would.” “They told you I would. Whoever told you's another lunatic. I never heard the beat of it. Who's they?” “Why, everybody. They all said so, m'am.” It was all she could do to hold in; and her eyes snapped, and her fingers worked like she wanted to scratch him; and she says: “Who's 'everybody'? Out with their names, or ther'll be an idiot short.” He got up and looked distressed, and fumbled his hat, and says: “I'm sorry, and I warn't expecting it. They told me to. They all told me to. They all said, kiss her; and said she'd like it. They all said it—every one of them. But I'm sorry, m'am, and I won't do it no more—I won't, honest.” “You won't, won't you? Well, I sh'd reckon you won't!” “No'm, I'm honest about it; I won't ever do it again—till you ask me.” “Till I ask you! Well, I never see the beat of it in my born days! I lay you'll be the Methusalem-numskull of creation before ever I ask you—or the likes of you.” “Well,” he says, “it does surprise me so. I can't make it out, somehow. They said you would, and I thought you would. But—” He stopped and looked around slow, like he wished he could run across a friendly eye somewheres, and fetched up on the old gentleman's, and says, “Didn't you think she'd like me to kiss her, sir?” “Why, no; I—I—well, no, I b'lieve I didn't.” Then he looks on around the same way to me, and says: “Tom, didn't you think Aunt Sally 'd open out her arms and say, 'Sid Sawyer—'” “My land!” she says, breaking in and jumping for him, “you impudent young rascal, to fool a body so—” and was going to hug him, but he fended her off, and says: “No, not till you've asked me first.” So she didn't lose no time, but asked him; and hugged him and kissed him over and over again, and then turned him over to the old man, and he took what was left. And after they got a little quiet again she says: “Why, dear me, I never see such a surprise. We warn't looking for you at all, but only Tom. Sis never wrote to me about anybody coming but him.” “It's because it warn't intended for any of us to come but Tom,” he says; “but I begged and begged, and at the last minute she let me come, too; so, coming down the river, me and Tom thought it would be a first-rate surprise for him to come here to the house first, and for me to by and by tag along and drop in, and let on to be a stranger. But it was a mistake, Aunt Sally. This ain't no healthy place for a stranger to come.” “No—not impudent whelps, Sid. You ought to had your jaws boxed; I hain't been so put out since I don't know when. But I don't care, I don't mind the terms—I'd be willing to stand a thousand such jokes to have you here. Well, to think of that performance! I don't deny it, I was most putrified with astonishment when you give me that smack.” We had dinner out in that broad open passage betwixt the house and the kitchen; and there was things enough on that table for seven families—and all hot, too; none of your flabby, tough meat that's laid in a cupboard in a damp cellar all night and tastes like a hunk of old cold cannibal in the morning. Uncle Silas he asked a pretty long blessing over it, but it was worth it; and it didn't cool it a bit, neither, the way I've seen them kind of interruptions do lots of times. There was a considerable good deal of talk all the afternoon, and me and Tom was on the lookout all the time; but it warn't no use, they didn't happen to say nothing about any runaway nigger, and we was afraid to try to work up to it. But at supper, at night, one of the little boys says: “Pa, mayn't Tom and Sid and me go to the show?” “No,” says the old man, “I reckon there ain't going to be any; and you couldn't go if there was; because the runaway nigger told Burton and me all about that scandalous show, and Burton said he would tell the people; so I reckon they've drove the owdacious loafers out of town before this time.” So there it was!—but I couldn't help it. Tom and me was to sleep in the same room and bed; so, being tired, we bid good-night and went up to bed right after supper, and clumb out of the window and down the lightning-rod, and shoved for the town; for I didn't believe anybody was going to give the king and the duke a hint, and so if I didn't hurry up and give them one they'd get into trouble sure. On the road Tom he told me all about how it was reckoned I was murdered, and how pap disappeared pretty soon, and didn't come back no more, and what a stir there was when Jim run away; and I told Tom all about our Royal Nonesuch rapscallions, and as much of the raft voyage as I had time to; and as we struck into the town and up through the the middle of it--it was as much as half-after eight, then—here comes a raging rush of people with torches, and an awful whooping and yelling, and banging tin pans and blowing horns; and we jumped to one side to let them go by; and as they went by I see they had the king and the duke astraddle of a rail—that is, I knowed it was the king and the duke, though they was all over tar and feathers, and didn't look like nothing in the world that was human—just looked like a couple of monstrous big soldier-plumes. Well, it made me sick to see it; and I was sorry for them poor pitiful rascals, it seemed like I couldn't ever feel any hardness against them any more in the world. It was a dreadful thing to see. Human beings can be awful cruel to one another. We see we was too late—couldn't do no good. We asked some stragglers about it, and they said everybody went to the show looking very innocent; and laid low and kept dark till the poor old king was in the middle of his cavortings on the stage; then somebody give a signal, and the house rose up and went for them. So we poked along back home, and I warn't feeling so brash as I was before, but kind of ornery, and humble, and to blame, somehow—though I hadn't done nothing. But that's always the way; it don't make no difference whether you do right or wrong, a person's conscience ain't got no sense, and just goes for him anyway. If I had a yaller dog that didn't know no more than a person's conscience does I would pison him. It takes up more room than all the rest of a person's insides, and yet ain't no good, nohow. Tom Sawyer he says the same. CHAPTER XXXIV. WE stopped talking, and got to thinking. By and by Tom says: “Looky here, Huck, what fools we are to not think of it before! I bet I know where Jim is.” “No! Where?” “In that hut down by the ash-hopper. Why, looky here. When we was at dinner, didn't you see a nigger man go in there with some vittles?” “Yes.” “What did you think the vittles was for?” “For a dog.” “So 'd I. Well, it wasn't for a dog.” “Why?” “Because part of it was watermelon.” “So it was—I noticed it. Well, it does beat all that I never thought about a dog not eating watermelon. It shows how a body can see and don't see at the same time.” “Well, the nigger unlocked the padlock when he went in, and he locked it again when he came out. He fetched uncle a key about the time we got up from table—same key, I bet. Watermelon shows man, lock shows prisoner; and it ain't likely there's two prisoners on such a little plantation, and where the people's all so kind and good. Jim's the prisoner. All right—I'm glad we found it out detective fashion; I wouldn't give shucks for any other way. Now you work your mind, and study out a plan to steal Jim, and I will study out one, too; and we'll take the one we like the best.” What a head for just a boy to have! If I had Tom Sawyer's head I wouldn't trade it off to be a duke, nor mate of a steamboat, nor clown in a circus, nor nothing I can think of. I went to thinking out a plan, but only just to be doing something; I knowed very well where the right plan was going to come from. Pretty soon Tom says: “Ready?” “Yes,” I says. “All right—bring it out.” “My plan is this,” I says. "We can easy find out if it's Jim in there. Then get up my canoe to-morrow night, and fetch my raft over from the island. Then the first dark night that comes steal the key out of the old man's britches after he goes to bed, and shove off down the river on the raft with Jim, hiding daytimes and running nights, the way me and Jim used to do before. Wouldn't that plan work?” “Work? Why, cert'nly it would work, like rats a-fighting. But it's too blame' simple; there ain't nothing to it. What's the good of a plan that ain't no more trouble than that? It's as mild as goose-milk. Why, Huck, it wouldn't make no more talk than breaking into a soap factory.” I never said nothing, because I warn't expecting nothing different; but I knowed mighty well that whenever he got his plan ready it wouldn't have none of them objections to it. And it didn't. He told me what it was, and I see in a minute it was worth fifteen of mine for style, and would make Jim just as free a man as mine would, and maybe get us all killed besides. So I was satisfied, and said we would waltz in on it. I needn't tell what it was here, because I knowed it wouldn't stay the way, it was. I knowed he would be changing it around every which way as we went along, and heaving in new bullinesses wherever he got a chance. And that is what he done. Well, one thing was dead sure, and that was that Tom Sawyer was in earnest, and was actuly going to help steal that nigger out of slavery. That was the thing that was too many for me. Here was a boy that was respectable and well brung up; and had a character to lose; and folks at home that had characters; and he was bright and not leather-headed; and knowing and not ignorant; and not mean, but kind; and yet here he was, without any more pride, or rightness, or feeling, than to stoop to this business, and make himself a shame, and his family a shame, before everybody. I couldn't understand it no way at all. It was outrageous, and I knowed I ought to just up and tell him so; and so be his true friend, and let him quit the thing right where he was and save himself. And I did start to tell him; but he shut me up, and says: “Don't you reckon I know what I'm about? Don't I generly know what I'm about?” “Yes.” “Didn't I say I was going to help steal the nigger?” “Yes.” “Well, then.” That's all he said, and that's all I said. It warn't no use to say any more; because when he said he'd do a thing, he always done it. But I couldn't make out how he was willing to go into this thing; so I just let it go, and never bothered no more about it. If he was bound to have it so, I couldn't help it. When we got home the house was all dark and still; so we went on down to the hut by the ash-hopper for to examine it. We went through the yard so as to see what the hounds would do. They knowed us, and didn't make no more noise than country dogs is always doing when anything comes by in the night. When we got to the cabin we took a look at the front and the two sides; and on the side I warn't acquainted with—which was the north side—we found a square window-hole, up tolerable high, with just one stout board nailed across it. I says: “Here's the ticket. This hole's big enough for Jim to get through if we wrench off the board.” Tom says: “It's as simple as tit-tat-toe, three-in-a-row, and as easy as playing hooky. I should hope we can find a way that's a little more complicated than that, Huck Finn.” “Well, then,” I says, “how 'll it do to saw him out, the way I done before I was murdered that time?” “That's more like,” he says. "It's real mysterious, and troublesome, and good,” he says; “but I bet we can find a way that's twice as long. There ain't no hurry; le's keep on looking around.” Betwixt the hut and the fence, on the back side, was a lean-to that joined the hut at the eaves, and was made out of plank. It was as long as the hut, but narrow—only about six foot wide. The door to it was at the south end, and was padlocked. Tom he went to the soap-kettle and searched around, and fetched back the iron thing they lift the lid with; so he took it and prized out one of the staples. The chain fell down, and we opened the door and went in, and shut it, and struck a match, and see the shed was only built against a cabin and hadn't no connection with it; and there warn't no floor to the shed, nor nothing in it but some old rusty played-out hoes and spades and picks and a crippled plow. The match went out, and so did we, and shoved in the staple again, and the door was locked as good as ever. Tom was joyful. He says; “Now we're all right. We'll dig him out. It 'll take about a week!” Then we started for the house, and I went in the back door—you only have to pull a buckskin latch-string, they don't fasten the doors—but that warn't romantical enough for Tom Sawyer; no way would do him but he must climb up the lightning-rod. But after he got up half way about three times, and missed fire and fell every time, and the last time most busted his brains out, he thought he'd got to give it up; but after he was rested he allowed he would give her one more turn for luck, and this time he made the trip. In the morning we was up at break of day, and down to the nigger cabins to pet the dogs and make friends with the nigger that fed Jim—if it was Jim that was being fed. The niggers was just getting through breakfast and starting for the fields; and Jim's nigger was piling up a tin pan with bread and meat and things; and whilst the others was leaving, the key come from the house. This nigger had a good-natured, chuckle-headed face, and his wool was all tied up in little bunches with thread. That was to keep witches off. He said the witches was pestering him awful these nights, and making him see all kinds of strange things, and hear all kinds of strange words and noises, and he didn't believe he was ever witched so long before in his life. He got so worked up, and got to running on so about his troubles, he forgot all about what he'd been a-going to do. So Tom says: “What's the vittles for? Going to feed the dogs?” The nigger kind of smiled around gradually over his face, like when you heave a brickbat in a mud-puddle, and he says: “Yes, Mars Sid, A dog. Cur'us dog, too. Does you want to go en look at 'im?” “Yes.” I hunched Tom, and whispers: “You going, right here in the daybreak? that warn't the plan.” “No, it warn't; but it's the plan now.” So, drat him, we went along, but I didn't like it much. When we got in we couldn't hardly see anything, it was so dark; but Jim was there, sure enough, and could see us; and he sings out: “Why, Huck! En good lan'! ain' dat Misto Tom?” I just knowed how it would be; I just expected it. I didn't know nothing to do; and if I had I couldn't a done it, because that nigger busted in and says: “Why, de gracious sakes! do he know you genlmen?” We could see pretty well now. Tom he looked at the nigger, steady and kind of wondering, and says: “Does who know us?” “Why, dis-yer runaway nigger.” “I don't reckon he does; but what put that into your head?” “What put it dar? Didn' he jis' dis minute sing out like he knowed you?” Tom says, in a puzzled-up kind of way: “Well, that's mighty curious. Who sung out? when did he sing out? what did he sing out?” And turns to me, perfectly ca'm, and says, “Did you hear anybody sing out?” Of course there warn't nothing to be said but the one thing; so I says: “No; I ain't heard nobody say nothing.” Then he turns to Jim, and looks him over like he never see him before, and says: “Did you sing out?” “No, sah,” says Jim; “I hain't said nothing, sah.” “Not a word?” “No, sah, I hain't said a word.” “Did you ever see us before?” “No, sah; not as I knows on.” So Tom turns to the nigger, which was looking wild and distressed, and says, kind of severe: “What do you reckon's the matter with you, anyway? What made you think somebody sung out?” “Oh, it's de dad-blame' witches, sah, en I wisht I was dead, I do. Dey's awluz at it, sah, en dey do mos' kill me, dey sk'yers me so. Please to don't tell nobody 'bout it sah, er ole Mars Silas he'll scole me; 'kase he say dey ain't no witches. I jis' wish to goodness he was heah now—den what would he say! I jis' bet he couldn' fine no way to git aroun' it dis time. But it's awluz jis' so; people dat's sot, stays sot; dey won't look into noth'n'en fine it out f'r deyselves, en when you fine it out en tell um 'bout it, dey doan' b'lieve you.” Tom give him a dime, and said we wouldn't tell nobody; and told him to buy some more thread to tie up his wool with; and then looks at Jim, and says: “I wonder if Uncle Silas is going to hang this nigger. If I was to catch a nigger that was ungrateful enough to run away, I wouldn't give him up, I'd hang him.” And whilst the nigger stepped to the door to look at the dime and bite it to see if it was good, he whispers to Jim and says: “Don't ever let on to know us. And if you hear any digging going on nights, it's us; we're going to set you free.” Jim only had time to grab us by the hand and squeeze it; then the nigger come back, and we said we'd come again some time if the nigger wanted us to; and he said he would, more particular if it was dark, because the witches went for him mostly in the dark, and it was good to have folks around then. CHAPTER XXXV. IT would be most an hour yet till breakfast, so we left and struck down into the woods; because Tom said we got to have some light to see how to dig by, and a lantern makes too much, and might get us into trouble; what we must have was a lot of them rotten chunks that's called fox-fire, and just makes a soft kind of a glow when you lay them in a dark place. We fetched an armful and hid it in the weeds, and set down to rest, and Tom says, kind of dissatisfied: “Blame it, this whole thing is just as easy and awkward as it can be. And so it makes it so rotten difficult to get up a difficult plan. There ain't no watchman to be drugged—now there ought to be a watchman. There ain't even a dog to give a sleeping-mixture to. And there's Jim chained by one leg, with a ten-foot chain, to the leg of his bed: why, all you got to do is to lift up the bedstead and slip off the chain. And Uncle Silas he trusts everybody; sends the key to the punkin-headed nigger, and don't send nobody to watch the nigger. Jim could a got out of that window-hole before this, only there wouldn't be no use trying to travel with a ten-foot chain on his leg. Why, drat it, Huck, it's the stupidest arrangement I ever see. You got to invent all the difficulties. Well, we can't help it; we got to do the best we can with the materials we've got. Anyhow, there's one thing—there's more honor in getting him out through a lot of difficulties and dangers, where there warn't one of them furnished to you by the people who it was their duty to furnish them, and you had to contrive them all out of your own head. Now look at just that one thing of the lantern. When you come down to the cold facts, we simply got to let on that a lantern's resky. Why, we could work with a torchlight procession if we wanted to, I believe. Now, whilst I think of it, we got to hunt up something to make a saw out of the first chance we get.” “What do we want of a saw?” “What do we want of it? Hain't we got to saw the leg of Jim's bed off, so as to get the chain loose?” “Why, you just said a body could lift up the bedstead and slip the chain off.” “Well, if that ain't just like you, Huck Finn. You can get up the infant-schooliest ways of going at a thing. Why, hain't you ever read any books at all?—Baron Trenck, nor Casanova, nor Benvenuto Chelleeny, nor Henri IV., nor none of them heroes? Who ever heard of getting a prisoner loose in such an old-maidy way as that? No; the way all the best authorities does is to saw the bed-leg in two, and leave it just so, and swallow the sawdust, so it can't be found, and put some dirt and grease around the sawed place so the very keenest seneskal can't see no sign of it's being sawed, and thinks the bed-leg is perfectly sound. Then, the night you're ready, fetch the leg a kick, down she goes; slip off your chain, and there you are. Nothing to do but hitch your rope ladder to the battlements, shin down it, break your leg in the moat—because a rope ladder is nineteen foot too short, you know—and there's your horses and your trusty vassles, and they scoop you up and fling you across a saddle, and away you go to your native Langudoc, or Navarre, or wherever it is. It's gaudy, Huck. I wish there was a moat to this cabin. If we get time, the night of the escape, we'll dig one.” I says: “What do we want of a moat when we're going to snake him out from under the cabin?” But he never heard me. He had forgot me and everything else. He had his chin in his hand, thinking. Pretty soon he sighs and shakes his head; then sighs again, and says: “No, it wouldn't do—there ain't necessity enough for it.” “For what?” I says. “Why, to saw Jim's leg off,” he says. “Good land!” I says; “why, there ain't no necessity for it. And what would you want to saw his leg off for, anyway?” “Well, some of the best authorities has done it. They couldn't get the chain off, so they just cut their hand off and shoved. And a leg would be better still. But we got to let that go. There ain't necessity enough in this case; and, besides, Jim's a nigger, and wouldn't understand the reasons for it, and how it's the custom in Europe; so we'll let it go. But there's one thing—he can have a rope ladder; we can tear up our sheets and make him a rope ladder easy enough. And we can send it to him in a pie; it's mostly done that way. And I've et worse pies.” “Why, Tom Sawyer, how you talk,” I says; “Jim ain't got no use for a rope ladder.” “He has got use for it. How you talk, you better say; you don't know nothing about it. He's got to have a rope ladder; they all do.” “What in the nation can he do with it?” “Do with it? He can hide it in his bed, can't he?” That's what they all do; and he's got to, too. Huck, you don't ever seem to want to do anything that's regular; you want to be starting something fresh all the time. S'pose he don't do nothing with it? ain't it there in his bed, for a clew, after he's gone? and don't you reckon they'll want clews? Of course they will. And you wouldn't leave them any? That would be a pretty howdy-do, wouldn't it! I never heard of such a thing.” “Well,” I says, “if it's in the regulations, and he's got to have it, all right, let him have it; because I don't wish to go back on no regulations; but there's one thing, Tom Sawyer—if we go to tearing up our sheets to make Jim a rope ladder, we're going to get into trouble with Aunt Sally, just as sure as you're born. Now, the way I look at it, a hickry-bark ladder don't cost nothing, and don't waste nothing, and is just as good to load up a pie with, and hide in a straw tick, as any rag ladder you can start; and as for Jim, he ain't had no experience, and so he don't care what kind of a—” “Oh, shucks, Huck Finn, if I was as ignorant as you I'd keep still—that's what I'D do. Who ever heard of a state prisoner escaping by a hickry-bark ladder? Why, it's perfectly ridiculous.” “Well, all right, Tom, fix it your own way; but if you'll take my advice, you'll let me borrow a sheet off of the clothesline.” He said that would do. And that gave him another idea, and he says: “Borrow a shirt, too.” “What do we want of a shirt, Tom?” “Want it for Jim to keep a journal on.” “Journal your granny—Jim can't write.” “S'pose he can't write—he can make marks on the shirt, can't he, if we make him a pen out of an old pewter spoon or a piece of an old iron barrel-hoop?” “Why, Tom, we can pull a feather out of a goose and make him a better one; and quicker, too.” “Prisoners don't have geese running around the donjon-keep to pull pens out of, you muggins. They always make their pens out of the hardest, toughest, troublesomest piece of old brass candlestick or something like that they can get their hands on; and it takes them weeks and weeks and months and months to file it out, too, because they've got to do it by rubbing it on the wall. They wouldn't use a goose-quill if they had it. It ain't regular.” “Well, then, what'll we make him the ink out of?” “Many makes it out of iron-rust and tears; but that's the common sort and women; the best authorities uses their own blood. Jim can do that; and when he wants to send any little common ordinary mysterious message to let the world know where he's captivated, he can write it on the bottom of a tin plate with a fork and throw it out of the window. The Iron Mask always done that, and it's a blame' good way, too.” “Jim ain't got no tin plates. They feed him in a pan.” “That ain't nothing; we can get him some.” “Can't nobody read his plates.” “That ain't got anything to do with it, Huck Finn. All he's got to do is to write on the plate and throw it out. You don't have to be able to read it. Why, half the time you can't read anything a prisoner writes on a tin plate, or anywhere else.” “Well, then, what's the sense in wasting the plates?” “Why, blame it all, it ain't the prisoner's plates.” “But it's somebody's plates, ain't it?” “Well, spos'n it is? What does the prisoner care whose—” He broke off there, because we heard the breakfast-horn blowing. So we cleared out for the house. Along during the morning I borrowed a sheet and a white shirt off of the clothes-line; and I found an old sack and put them in it, and we went down and got the fox-fire, and put that in too. I called it borrowing, because that was what pap always called it; but Tom said it warn't borrowing, it was stealing. He said we was representing prisoners; and prisoners don't care how they get a thing so they get it, and nobody don't blame them for it, either. It ain't no crime in a prisoner to steal the thing he needs to get away with, Tom said; it's his right; and so, as long as we was representing a prisoner, we had a perfect right to steal anything on this place we had the least use for to get ourselves out of prison with. He said if we warn't prisoners it would be a very different thing, and nobody but a mean, ornery person would steal when he warn't a prisoner. So we allowed we would steal everything there was that come handy. And yet he made a mighty fuss, one day, after that, when I stole a watermelon out of the nigger-patch and eat it; and he made me go and give the niggers a dime without telling them what it was for. Tom said that what he meant was, we could steal anything we needed. Well, I says, I needed the watermelon. But he said I didn't need it to get out of prison with; there's where the difference was. He said if I'd a wanted it to hide a knife in, and smuggle it to Jim to kill the seneskal with, it would a been all right. So I let it go at that, though I couldn't see no advantage in my representing a prisoner if I got to set down and chaw over a lot of gold-leaf distinctions like that every time I see a chance to hog a watermelon. Well, as I was saying, we waited that morning till everybody was settled down to business, and nobody in sight around the yard; then Tom he carried the sack into the lean-to whilst I stood off a piece to keep watch. By and by he come out, and we went and set down on the woodpile to talk. He says: “Everything's all right now except tools; and that's easy fixed.” “Tools?” I says. “Yes.” “Tools for what?” “Why, to dig with. We ain't a-going to gnaw him out, are we?” “Ain't them old crippled picks and things in there good enough to dig a nigger out with?” I says. He turns on me, looking pitying enough to make a body cry, and says: “Huck Finn, did you ever hear of a prisoner having picks and shovels, and all the modern conveniences in his wardrobe to dig himself out with? Now I want to ask you—if you got any reasonableness in you at all—what kind of a show would that give him to be a hero? Why, they might as well lend him the key and done with it. Picks and shovels—why, they wouldn't furnish 'em to a king.” “Well, then,” I says, “if we don't want the picks and shovels, what do we want?” “A couple of case-knives.” “To dig the foundations out from under that cabin with?” “Yes.” “Confound it, it's foolish, Tom.” “It don't make no difference how foolish it is, it's the right way—and it's the regular way. And there ain't no other way, that ever I heard of, and I've read all the books that gives any information about these things. They always dig out with a case-knife—and not through dirt, mind you; generly it's through solid rock. And it takes them weeks and weeks and weeks, and for ever and ever. Why, look at one of them prisoners in the bottom dungeon of the Castle Deef, in the harbor of Marseilles, that dug himself out that way; how long was he at it, you reckon?” “I don't know.” “Well, guess.” “I don't know. A month and a half.” “Thirty-seven year—and he come out in China. That's the kind. I wish the bottom of this fortress was solid rock.” “Jim don't know nobody in China.” “What's that got to do with it? Neither did that other fellow. But you're always a-wandering off on a side issue. Why can't you stick to the main point?” “All right—I don't care where he comes out, so he comes out; and Jim don't, either, I reckon. But there's one thing, anyway—Jim's too old to be dug out with a case-knife. He won't last.” “Yes he will last, too. You don't reckon it's going to take thirty-seven years to dig out through a dirt foundation, do you?” “How long will it take, Tom?” “Well, we can't resk being as long as we ought to, because it mayn't take very long for Uncle Silas to hear from down there by New Orleans. He'll hear Jim ain't from there. Then his next move will be to advertise Jim, or something like that. So we can't resk being as long digging him out as we ought to. By rights I reckon we ought to be a couple of years; but we can't. Things being so uncertain, what I recommend is this: that we really dig right in, as quick as we can; and after that, we can let on, to ourselves, that we was at it thirty-seven years. Then we can snatch him out and rush him away the first time there's an alarm. Yes, I reckon that 'll be the best way.” “Now, there's sense in that,” I says. "Letting on don't cost nothing; letting on ain't no trouble; and if it's any object, I don't mind letting on we was at it a hundred and fifty year. It wouldn't strain me none, after I got my hand in. So I'll mosey along now, and smouch a couple of case-knives.” “Smouch three,” he says; “we want one to make a saw out of.” “Tom, if it ain't unregular and irreligious to sejest it,” I says, “there's an old rusty saw-blade around yonder sticking under the weather-boarding behind the smoke-house.” He looked kind of weary and discouraged-like, and says: “It ain't no use to try to learn you nothing, Huck. Run along and smouch the knives—three of them.” So I done it. CHAPTER XXXVI. AS soon as we reckoned everybody was asleep that night we went down the lightning-rod, and shut ourselves up in the lean-to, and got out our pile of fox-fire, and went to work. We cleared everything out of the way, about four or five foot along the middle of the bottom log. Tom said he was right behind Jim's bed now, and we'd dig in under it, and when we got through there couldn't nobody in the cabin ever know there was any hole there, because Jim's counter-pin hung down most to the ground, and you'd have to raise it up and look under to see the hole. So we dug and dug with the case-knives till most midnight; and then we was dog-tired, and our hands was blistered, and yet you couldn't see we'd done anything hardly. At last I says: “This ain't no thirty-seven year job; this is a thirty-eight year job, Tom Sawyer.” He never said nothing. But he sighed, and pretty soon he stopped digging, and then for a good little while I knowed that he was thinking. Then he says: “It ain't no use, Huck, it ain't a-going to work. If we was prisoners it would, because then we'd have as many years as we wanted, and no hurry; and we wouldn't get but a few minutes to dig, every day, while they was changing watches, and so our hands wouldn't get blistered, and we could keep it up right along, year in and year out, and do it right, and the way it ought to be done. But we can't fool along; we got to rush; we ain't got no time to spare. If we was to put in another night this way we'd have to knock off for a week to let our hands get well—couldn't touch a case-knife with them sooner.” “Well, then, what we going to do, Tom?” “I'll tell you. It ain't right, and it ain't moral, and I wouldn't like it to get out; but there ain't only just the one way: we got to dig him out with the picks, and let on it's case-knives.” “Now you're talking!” I says; “your head gets leveler and leveler all the time, Tom Sawyer,” I says. "Picks is the thing, moral or no moral; and as for me, I don't care shucks for the morality of it, nohow. When I start in to steal a nigger, or a watermelon, or a Sunday-school book, I ain't no ways particular how it's done so it's done. What I want is my nigger; or what I want is my watermelon; or what I want is my Sunday-school book; and if a pick's the handiest thing, that's the thing I'm a-going to dig that nigger or that watermelon or that Sunday-school book out with; and I don't give a dead rat what the authorities thinks about it nuther.” “Well,” he says, “there's excuse for picks and letting-on in a case like this; if it warn't so, I wouldn't approve of it, nor I wouldn't stand by and see the rules broke—because right is right, and wrong is wrong, and a body ain't got no business doing wrong when he ain't ignorant and knows better. It might answer for you to dig Jim out with a pick, without any letting on, because you don't know no better; but it wouldn't for me, because I do know better. Gimme a case-knife.” He had his own by him, but I handed him mine. He flung it down, and says: “Gimme a case-knife.” I didn't know just what to do—but then I thought. I scratched around amongst the old tools, and got a pickaxe and give it to him, and he took it and went to work, and never said a word. He was always just that particular. Full of principle. So then I got a shovel, and then we picked and shoveled, turn about, and made the fur fly. We stuck to it about a half an hour, which was as long as we could stand up; but we had a good deal of a hole to show for it. When I got up stairs I looked out at the window and see Tom doing his level best with the lightning-rod, but he couldn't come it, his hands was so sore. At last he says: “It ain't no use, it can't be done. What you reckon I better do? Can't you think of no way?” “Yes,” I says, “but I reckon it ain't regular. Come up the stairs, and let on it's a lightning-rod.” So he done it. Next day Tom stole a pewter spoon and a brass candlestick in the house, for to make some pens for Jim out of, and six tallow candles; and I hung around the nigger cabins and laid for a chance, and stole three tin plates. Tom says it wasn't enough; but I said nobody wouldn't ever see the plates that Jim throwed out, because they'd fall in the dog-fennel and jimpson weeds under the window-hole—then we could tote them back and he could use them over again. So Tom was satisfied. Then he says: “Now, the thing to study out is, how to get the things to Jim.” “Take them in through the hole,” I says, “when we get it done.” He only just looked scornful, and said something about nobody ever heard of such an idiotic idea, and then he went to studying. By and by he said he had ciphered out two or three ways, but there warn't no need to decide on any of them yet. Said we'd got to post Jim first. That night we went down the lightning-rod a little after ten, and took one of the candles along, and listened under the window-hole, and heard Jim snoring; so we pitched it in, and it didn't wake him. Then we whirled in with the pick and shovel, and in about two hours and a half the job was done. We crept in under Jim's bed and into the cabin, and pawed around and found the candle and lit it, and stood over Jim awhile, and found him looking hearty and healthy, and then we woke him up gentle and gradual. He was so glad to see us he most cried; and called us honey, and all the pet names he could think of; and was for having us hunt up a cold-chisel to cut the chain off of his leg with right away, and clearing out without losing any time. But Tom he showed him how unregular it would be, and set down and told him all about our plans, and how we could alter them in a minute any time there was an alarm; and not to be the least afraid, because we would see he got away, sure. So Jim he said it was all right, and we set there and talked over old times awhile, and then Tom asked a lot of questions, and when Jim told him Uncle Silas come in every day or two to pray with him, and Aunt Sally come in to see if he was comfortable and had plenty to eat, and both of them was kind as they could be, Tom says: “Now I know how to fix it. We'll send you some things by them.” I said, “Don't do nothing of the kind; it's one of the most jackass ideas I ever struck;” but he never paid no attention to me; went right on. It was his way when he'd got his plans set. So he told Jim how we'd have to smuggle in the rope-ladder pie and other large things by Nat, the nigger that fed him, and he must be on the lookout, and not be surprised, and not let Nat see him open them; and we would put small things in uncle's coat-pockets and he must steal them out; and we would tie things to aunt's apron-strings or put them in her apron-pocket, if we got a chance; and told him what they would be and what they was for. And told him how to keep a journal on the shirt with his blood, and all that. He told him everything. Jim he couldn't see no sense in the most of it, but he allowed we was white folks and knowed better than him; so he was satisfied, and said he would do it all just as Tom said. Jim had plenty corn-cob pipes and tobacco; so we had a right down good sociable time; then we crawled out through the hole, and so home to bed, with hands that looked like they'd been chawed. Tom was in high spirits. He said it was the best fun he ever had in his life, and the most intellectural; and said if he only could see his way to it we would keep it up all the rest of our lives and leave Jim to our children to get out; for he believed Jim would come to like it better and better the more he got used to it. He said that in that way it could be strung out to as much as eighty year, and would be the best time on record. And he said it would make us all celebrated that had a hand in it. In the morning we went out to the woodpile and chopped up the brass candlestick into handy sizes, and Tom put them and the pewter spoon in his pocket. Then we went to the nigger cabins, and while I got Nat's notice off, Tom shoved a piece of candlestick into the middle of a corn-pone that was in Jim's pan, and we went along with Nat to see how it would work, and it just worked noble; when Jim bit into it it most mashed all his teeth out; and there warn't ever anything could a worked better. Tom said so himself. Jim he never let on but what it was only just a piece of rock or something like that that's always getting into bread, you know; but after that he never bit into nothing but what he jabbed his fork into it in three or four places first. And whilst we was a-standing there in the dimmish light, here comes a couple of the hounds bulging in from under Jim's bed; and they kept on piling in till there was eleven of them, and there warn't hardly room in there to get your breath. By jings, we forgot to fasten that lean-to door! The nigger Nat he only just hollered “Witches” once, and keeled over on to the floor amongst the dogs, and begun to groan like he was dying. Tom jerked the door open and flung out a slab of Jim's meat, and the dogs went for it, and in two seconds he was out himself and back again and shut the door, and I knowed he'd fixed the other door too. Then he went to work on the nigger, coaxing him and petting him, and asking him if he'd been imagining he saw something again. He raised up, and blinked his eyes around, and says: “Mars Sid, you'll say I's a fool, but if I didn't b'lieve I see most a million dogs, er devils, er some'n, I wisht I may die right heah in dese tracks. I did, mos' sholy. Mars Sid, I felt um—I felt um, sah; dey was all over me. Dad fetch it, I jis' wisht I could git my han's on one er dem witches jis' wunst—on'y jis' wunst—it's all I'd ast. But mos'ly I wisht dey'd lemme 'lone, I does.” Tom says: “Well, I tell you what I think. What makes them come here just at this runaway nigger's breakfast-time? It's because they're hungry; that's the reason. You make them a witch pie; that's the thing for you to do.” “But my lan', Mars Sid, how's I gwyne to make 'm a witch pie? I doan' know how to make it. I hain't ever hearn er sich a thing b'fo'.” “Well, then, I'll have to make it myself.” “Will you do it, honey?—will you? I'll wusshup de groun' und' yo' foot, I will!” “All right, I'll do it, seeing it's you, and you've been good to us and showed us the runaway nigger. But you got to be mighty careful. When we come around, you turn your back; and then whatever we've put in the pan, don't you let on you see it at all. And don't you look when Jim unloads the pan—something might happen, I don't know what. And above all, don't you handle the witch-things.” “Hannel 'M, Mars Sid? What is you a-talkin' 'bout? I wouldn' lay de weight er my finger on um, not f'r ten hund'd thous'n billion dollars, I wouldn't.” CHAPTER XXXVII. THAT was all fixed. So then we went away and went to the rubbage-pile in the back yard, where they keep the old boots, and rags, and pieces of bottles, and wore-out tin things, and all such truck, and scratched around and found an old tin washpan, and stopped up the holes as well as we could, to bake the pie in, and took it down cellar and stole it full of flour and started for breakfast, and found a couple of shingle-nails that Tom said would be handy for a prisoner to scrabble his name and sorrows on the dungeon walls with, and dropped one of them in Aunt Sally's apron-pocket which was hanging on a chair, and t'other we stuck in the band of Uncle Silas's hat, which was on the bureau, because we heard the children say their pa and ma was going to the runaway nigger's house this morning, and then went to breakfast, and Tom dropped the pewter spoon in Uncle Silas's coat-pocket, and Aunt Sally wasn't come yet, so we had to wait a little while. And when she come she was hot and red and cross, and couldn't hardly wait for the blessing; and then she went to sluicing out coffee with one hand and cracking the handiest child's head with her thimble with the other, and says: “I've hunted high and I've hunted low, and it does beat all what has become of your other shirt.” My heart fell down amongst my lungs and livers and things, and a hard piece of corn-crust started down my throat after it and got met on the road with a cough, and was shot across the table, and took one of the children in the eye and curled him up like a fishing-worm, and let a cry out of him the size of a warwhoop, and Tom he turned kinder blue around the gills, and it all amounted to a considerable state of things for about a quarter of a minute or as much as that, and I would a sold out for half price if there was a bidder. But after that we was all right again—it was the sudden surprise of it that knocked us so kind of cold. Uncle Silas he says: “It's most uncommon curious, I can't understand it. I know perfectly well I took it off, because—” “Because you hain't got but one on. Just listen at the man! I know you took it off, and know it by a better way than your wool-gethering memory, too, because it was on the clo's-line yesterday—I see it there myself. But it's gone, that's the long and the short of it, and you'll just have to change to a red flann'l one till I can get time to make a new one. And it 'll be the third I've made in two years. It just keeps a body on the jump to keep you in shirts; and whatever you do manage to do with 'm all is more'n I can make out. A body 'd think you would learn to take some sort of care of 'em at your time of life.” “I know it, Sally, and I do try all I can. But it oughtn't to be altogether my fault, because, you know, I don't see them nor have nothing to do with them except when they're on me; and I don't believe I've ever lost one of them off of me.” “Well, it ain't your fault if you haven't, Silas; you'd a done it if you could, I reckon. And the shirt ain't all that's gone, nuther. Ther's a spoon gone; and that ain't all. There was ten, and now ther's only nine. The calf got the shirt, I reckon, but the calf never took the spoon, that's certain.” “Why, what else is gone, Sally?” “Ther's six candles gone—that's what. The rats could a got the candles, and I reckon they did; I wonder they don't walk off with the whole place, the way you're always going to stop their holes and don't do it; and if they warn't fools they'd sleep in your hair, Silas—you'd never find it out; but you can't lay the spoon on the rats, and that I know.” “Well, Sally, I'm in fault, and I acknowledge it; I've been remiss; but I won't let to-morrow go by without stopping up them holes.” “Oh, I wouldn't hurry; next year 'll do. Matilda Angelina Araminta Phelps!” Whack comes the thimble, and the child snatches her claws out of the sugar-bowl without fooling around any. Just then the nigger woman steps on to the passage, and says: “Missus, dey's a sheet gone.” “A sheet gone! Well, for the land's sake!” “I'll stop up them holes to-day,” says Uncle Silas, looking sorrowful. “Oh, do shet up!—s'pose the rats took the sheet? where's it gone, Lize?” “Clah to goodness I hain't no notion, Miss' Sally. She wuz on de clo'sline yistiddy, but she done gone: she ain' dah no mo' now.” “I reckon the world is coming to an end. I never see the beat of it in all my born days. A shirt, and a sheet, and a spoon, and six can—” “Missus,” comes a young yaller wench, “dey's a brass cannelstick miss'n.” “Cler out from here, you hussy, er I'll take a skillet to ye!” Well, she was just a-biling. I begun to lay for a chance; I reckoned I would sneak out and go for the woods till the weather moderated. She kept a-raging right along, running her insurrection all by herself, and everybody else mighty meek and quiet; and at last Uncle Silas, looking kind of foolish, fishes up that spoon out of his pocket. She stopped, with her mouth open and her hands up; and as for me, I wished I was in Jeruslem or somewheres. But not long, because she says: “It's just as I expected. So you had it in your pocket all the time; and like as not you've got the other things there, too. How'd it get there?” “I reely don't know, Sally,” he says, kind of apologizing, “or you know I would tell. I was a-studying over my text in Acts Seventeen before breakfast, and I reckon I put it in there, not noticing, meaning to put my Testament in, and it must be so, because my Testament ain't in; but I'll go and see; and if the Testament is where I had it, I'll know I didn't put it in, and that will show that I laid the Testament down and took up the spoon, and—” “Oh, for the land's sake! Give a body a rest! Go 'long now, the whole kit and biling of ye; and don't come nigh me again till I've got back my peace of mind.” I'D a heard her if she'd a said it to herself, let alone speaking it out; and I'd a got up and obeyed her if I'd a been dead. As we was passing through the setting-room the old man he took up his hat, and the shingle-nail fell out on the floor, and he just merely picked it up and laid it on the mantel-shelf, and never said nothing, and went out. Tom see him do it, and remembered about the spoon, and says: “Well, it ain't no use to send things by him no more, he ain't reliable.” Then he says: "But he done us a good turn with the spoon, anyway, without knowing it, and so we'll go and do him one without him knowing it—stop up his rat-holes.” There was a noble good lot of them down cellar, and it took us a whole hour, but we done the job tight and good and shipshape. Then we heard steps on the stairs, and blowed out our light and hid; and here comes the old man, with a candle in one hand and a bundle of stuff in t'other, looking as absent-minded as year before last. He went a mooning around, first to one rat-hole and then another, till he'd been to them all. Then he stood about five minutes, picking tallow-drip off of his candle and thinking. Then he turns off slow and dreamy towards the stairs, saying: “Well, for the life of me I can't remember when I done it. I could show her now that I warn't to blame on account of the rats. But never mind—let it go. I reckon it wouldn't do no good.” And so he went on a-mumbling up stairs, and then we left. He was a mighty nice old man. And always is. Tom was a good deal bothered about what to do for a spoon, but he said we'd got to have it; so he took a think. When he had ciphered it out he told me how we was to do; then we went and waited around the spoon-basket till we see Aunt Sally coming, and then Tom went to counting the spoons and laying them out to one side, and I slid one of them up my sleeve, and Tom says: “Why, Aunt Sally, there ain't but nine spoons yet.” She says: “Go 'long to your play, and don't bother me. I know better, I counted 'm myself.” “Well, I've counted them twice, Aunty, and I can't make but nine.” She looked out of all patience, but of course she come to count—anybody would. “I declare to gracious ther' ain't but nine!” she says. "Why, what in the world—plague take the things, I'll count 'm again.” So I slipped back the one I had, and when she got done counting, she says: “Hang the troublesome rubbage, ther's ten now!” and she looked huffy and bothered both. But Tom says: “Why, Aunty, I don't think there's ten.” “You numskull, didn't you see me count 'm?” “I know, but—” “Well, I'll count 'm again.” So I smouched one, and they come out nine, same as the other time. Well, she was in a tearing way—just a-trembling all over, she was so mad. But she counted and counted till she got that addled she'd start to count in the basket for a spoon sometimes; and so, three times they come out right, and three times they come out wrong. Then she grabbed up the basket and slammed it across the house and knocked the cat galley-west; and she said cle'r out and let her have some peace, and if we come bothering around her again betwixt that and dinner she'd skin us. So we had the odd spoon, and dropped it in her apron-pocket whilst she was a-giving us our sailing orders, and Jim got it all right, along with her shingle nail, before noon. We was very well satisfied with this business, and Tom allowed it was worth twice the trouble it took, because he said now she couldn't ever count them spoons twice alike again to save her life; and wouldn't believe she'd counted them right if she did; and said that after she'd about counted her head off for the next three days he judged she'd give it up and offer to kill anybody that wanted her to ever count them any more. So we put the sheet back on the line that night, and stole one out of her closet; and kept on putting it back and stealing it again for a couple of days till she didn't know how many sheets she had any more, and she didn't care, and warn't a-going to bullyrag the rest of her soul out about it, and wouldn't count them again not to save her life; she druther die first. So we was all right now, as to the shirt and the sheet and the spoon and the candles, by the help of the calf and the rats and the mixed-up counting; and as to the candlestick, it warn't no consequence, it would blow over by and by. But that pie was a job; we had no end of trouble with that pie. We fixed it up away down in the woods, and cooked it there; and we got it done at last, and very satisfactory, too; but not all in one day; and we had to use up three wash-pans full of flour before we got through, and we got burnt pretty much all over, in places, and eyes put out with the smoke; because, you see, we didn't want nothing but a crust, and we couldn't prop it up right, and she would always cave in. But of course we thought of the right way at last—which was to cook the ladder, too, in the pie. So then we laid in with Jim the second night, and tore up the sheet all in little strings and twisted them together, and long before daylight we had a lovely rope that you could a hung a person with. We let on it took nine months to make it. And in the forenoon we took it down to the woods, but it wouldn't go into the pie. Being made of a whole sheet, that way, there was rope enough for forty pies if we'd a wanted them, and plenty left over for soup, or sausage, or anything you choose. We could a had a whole dinner. But we didn't need it. All we needed was just enough for the pie, and so we throwed the rest away. We didn't cook none of the pies in the wash-pan—afraid the solder would melt; but Uncle Silas he had a noble brass warming-pan which he thought considerable of, because it belonged to one of his ancesters with a long wooden handle that come over from England with William the Conqueror in the Mayflower or one of them early ships and was hid away up garret with a lot of other old pots and things that was valuable, not on account of being any account, because they warn't, but on account of them being relicts, you know, and we snaked her out, private, and took her down there, but she failed on the first pies, because we didn't know how, but she come up smiling on the last one. We took and lined her with dough, and set her in the coals, and loaded her up with rag rope, and put on a dough roof, and shut down the lid, and put hot embers on top, and stood off five foot, with the long handle, cool and comfortable, and in fifteen minutes she turned out a pie that was a satisfaction to look at. But the person that et it would want to fetch a couple of kags of toothpicks along, for if that rope ladder wouldn't cramp him down to business I don't know nothing what I'm talking about, and lay him in enough stomach-ache to last him till next time, too. Nat didn't look when we put the witch pie in Jim's pan; and we put the three tin plates in the bottom of the pan under the vittles; and so Jim got everything all right, and as soon as he was by himself he busted into the pie and hid the rope ladder inside of his straw tick, and scratched some marks on a tin plate and throwed it out of the window-hole. CHAPTER XXXVIII. MAKING them pens was a distressid tough job, and so was the saw; and Jim allowed the inscription was going to be the toughest of all. That's the one which the prisoner has to scrabble on the wall. But he had to have it; Tom said he'd got to; there warn't no case of a state prisoner not scrabbling his inscription to leave behind, and his coat of arms. “Look at Lady Jane Grey,” he says; “look at Gilford Dudley; look at old Northumberland! Why, Huck, s'pose it is considerble trouble?—what you going to do?—how you going to get around it? Jim's got to do his inscription and coat of arms. They all do.” Jim says: “Why, Mars Tom, I hain't got no coat o' arm; I hain't got nuffn but dish yer ole shirt, en you knows I got to keep de journal on dat.” “Oh, you don't understand, Jim; a coat of arms is very different.” “Well,” I says, “Jim's right, anyway, when he says he ain't got no coat of arms, because he hain't.” “I reckon I knowed that,” Tom says, “but you bet he'll have one before he goes out of this—because he's going out right, and there ain't going to be no flaws in his record.” So whilst me and Jim filed away at the pens on a brickbat apiece, Jim a-making his'n out of the brass and I making mine out of the spoon, Tom set to work to think out the coat of arms. By and by he said he'd struck so many good ones he didn't hardly know which to take, but there was one which he reckoned he'd decide on. He says: “On the scutcheon we'll have a bend or in the dexter base, a saltire murrey in the fess, with a dog, couchant, for common charge, and under his foot a chain embattled, for slavery, with a chevron vert in a chief engrailed, and three invected lines on a field azure, with the nombril points rampant on a dancette indented; crest, a runaway nigger, sable, with his bundle over his shoulder on a bar sinister; and a couple of gules for supporters, which is you and me; motto, Maggiore Fretta, Minore Otto. Got it out of a book—means the more haste the less speed.” “Geewhillikins,” I says, “but what does the rest of it mean?” “We ain't got no time to bother over that,” he says; “we got to dig in like all git-out.” “Well, anyway,” I says, “what's some of it? What's a fess?” “A fess—a fess is—you don't need to know what a fess is. I'll show him how to make it when he gets to it.” “Shucks, Tom,” I says, “I think you might tell a person. What's a bar sinister?” “Oh, I don't know. But he's got to have it. All the nobility does.” That was just his way. If it didn't suit him to explain a thing to you, he wouldn't do it. You might pump at him a week, it wouldn't make no difference. He'd got all that coat of arms business fixed, so now he started in to finish up the rest of that part of the work, which was to plan out a mournful inscription—said Jim got to have one, like they all done. He made up a lot, and wrote them out on a paper, and read them off, so: 1. Here a captive heart busted. 2. Here a poor prisoner, forsook by the world and friends, fretted his sorrowful life. 3. Here a lonely heart broke, and a worn spirit went to its rest, after thirty-seven years of solitary captivity. 4. Here, homeless and friendless, after thirty-seven years of bitter captivity, perished a noble stranger, natural son of Louis XIV. Tom's voice trembled whilst he was reading them, and he most broke down. When he got done he couldn't no way make up his mind which one for Jim to scrabble on to the wall, they was all so good; but at last he allowed he would let him scrabble them all on. Jim said it would take him a year to scrabble such a lot of truck on to the logs with a nail, and he didn't know how to make letters, besides; but Tom said he would block them out for him, and then he wouldn't have nothing to do but just follow the lines. Then pretty soon he says: “Come to think, the logs ain't a-going to do; they don't have log walls in a dungeon: we got to dig the inscriptions into a rock. We'll fetch a rock.” Jim said the rock was worse than the logs; he said it would take him such a pison long time to dig them into a rock he wouldn't ever get out. But Tom said he would let me help him do it. Then he took a look to see how me and Jim was getting along with the pens. It was most pesky tedious hard work and slow, and didn't give my hands no show to get well of the sores, and we didn't seem to make no headway, hardly; so Tom says: “I know how to fix it. We got to have a rock for the coat of arms and mournful inscriptions, and we can kill two birds with that same rock. There's a gaudy big grindstone down at the mill, and we'll smouch it, and carve the things on it, and file out the pens and the saw on it, too.” It warn't no slouch of an idea; and it warn't no slouch of a grindstone nuther; but we allowed we'd tackle it. It warn't quite midnight yet, so we cleared out for the mill, leaving Jim at work. We smouched the grindstone, and set out to roll her home, but it was a most nation tough job. Sometimes, do what we could, we couldn't keep her from falling over, and she come mighty near mashing us every time. Tom said she was going to get one of us, sure, before we got through. We got her half way; and then we was plumb played out, and most drownded with sweat. We see it warn't no use; we got to go and fetch Jim. So he raised up his bed and slid the chain off of the bed-leg, and wrapt it round and round his neck, and we crawled out through our hole and down there, and Jim and me laid into that grindstone and walked her along like nothing; and Tom superintended. He could out-superintend any boy I ever see. He knowed how to do everything. Our hole was pretty big, but it warn't big enough to get the grindstone through; but Jim he took the pick and soon made it big enough. Then Tom marked out them things on it with the nail, and set Jim to work on them, with the nail for a chisel and an iron bolt from the rubbage in the lean-to for a hammer, and told him to work till the rest of his candle quit on him, and then he could go to bed, and hide the grindstone under his straw tick and sleep on it. Then we helped him fix his chain back on the bed-leg, and was ready for bed ourselves. But Tom thought of something, and says: “You got any spiders in here, Jim?” “No, sah, thanks to goodness I hain't, Mars Tom.” “All right, we'll get you some.” “But bless you, honey, I doan' want none. I's afeard un um. I jis' 's soon have rattlesnakes aroun'.” Tom thought a minute or two, and says: “It's a good idea. And I reckon it's been done. It must a been done; it stands to reason. Yes, it's a prime good idea. Where could you keep it?” “Keep what, Mars Tom?” “Why, a rattlesnake.” “De goodness gracious alive, Mars Tom! Why, if dey was a rattlesnake to come in heah I'd take en bust right out thoo dat log wall, I would, wid my head.” “Why, Jim, you wouldn't be afraid of it after a little. You could tame it.” “Tame it!” “Yes—easy enough. Every animal is grateful for kindness and petting, and they wouldn't think of hurting a person that pets them. Any book will tell you that. You try—that's all I ask; just try for two or three days. Why, you can get him so, in a little while, that he'll love you; and sleep with you; and won't stay away from you a minute; and will let you wrap him round your neck and put his head in your mouth.” “Please, Mars Tom—doan' talk so! I can't stan' it! He'd let me shove his head in my mouf—fer a favor, hain't it? I lay he'd wait a pow'ful long time 'fo' I ast him. En mo' en dat, I doan' want him to sleep wid me.” “Jim, don't act so foolish. A prisoner's got to have some kind of a dumb pet, and if a rattlesnake hain't ever been tried, why, there's more glory to be gained in your being the first to ever try it than any other way you could ever think of to save your life.” “Why, Mars Tom, I doan' want no sich glory. Snake take 'n bite Jim's chin off, den whah is de glory? No, sah, I doan' want no sich doin's.” “Blame it, can't you try? I only want you to try—you needn't keep it up if it don't work.” “But de trouble all done ef de snake bite me while I's a tryin' him. Mars Tom, I's willin' to tackle mos' anything 'at ain't onreasonable, but ef you en Huck fetches a rattlesnake in heah for me to tame, I's gwyne to leave, dat's shore.” “Well, then, let it go, let it go, if you're so bull-headed about it. We can get you some garter-snakes, and you can tie some buttons on their tails, and let on they're rattlesnakes, and I reckon that 'll have to do.” “I k'n stan' dem, Mars Tom, but blame' 'f I couldn' get along widout um, I tell you dat. I never knowed b'fo' 't was so much bother and trouble to be a prisoner.” “Well, it always is when it's done right. You got any rats around here?” “No, sah, I hain't seed none.” “Well, we'll get you some rats.” “Why, Mars Tom, I doan' want no rats. Dey's de dadblamedest creturs to 'sturb a body, en rustle roun' over 'im, en bite his feet, when he's tryin' to sleep, I ever see. No, sah, gimme g'yarter-snakes, 'f I's got to have 'm, but doan' gimme no rats; I hain' got no use f'r um, skasely.” “But, Jim, you got to have 'em—they all do. So don't make no more fuss about it. Prisoners ain't ever without rats. There ain't no instance of it. And they train them, and pet them, and learn them tricks, and they get to be as sociable as flies. But you got to play music to them. You got anything to play music on?” “I ain' got nuffn but a coase comb en a piece o' paper, en a juice-harp; but I reck'n dey wouldn' take no stock in a juice-harp.” “Yes they would they don't care what kind of music 'tis. A jews-harp's plenty good enough for a rat. All animals like music—in a prison they dote on it. Specially, painful music; and you can't get no other kind out of a jews-harp. It always interests them; they come out to see what's the matter with you. Yes, you're all right; you're fixed very well. You want to set on your bed nights before you go to sleep, and early in the mornings, and play your jews-harp; play 'The Last Link is Broken'—that's the thing that 'll scoop a rat quicker 'n anything else; and when you've played about two minutes you'll see all the rats, and the snakes, and spiders, and things begin to feel worried about you, and come. And they'll just fairly swarm over you, and have a noble good time.” “Yes, dey will, I reck'n, Mars Tom, but what kine er time is Jim havin'? Blest if I kin see de pint. But I'll do it ef I got to. I reck'n I better keep de animals satisfied, en not have no trouble in de house.” Tom waited to think it over, and see if there wasn't nothing else; and pretty soon he says: “Oh, there's one thing I forgot. Could you raise a flower here, do you reckon?” “I doan know but maybe I could, Mars Tom; but it's tolable dark in heah, en I ain' got no use f'r no flower, nohow, en she'd be a pow'ful sight o' trouble.” “Well, you try it, anyway. Some other prisoners has done it.” “One er dem big cat-tail-lookin' mullen-stalks would grow in heah, Mars Tom, I reck'n, but she wouldn't be wuth half de trouble she'd coss.” “Don't you believe it. We'll fetch you a little one and you plant it in the corner over there, and raise it. And don't call it mullen, call it Pitchiola—that's its right name when it's in a prison. And you want to water it with your tears.” “Why, I got plenty spring water, Mars Tom.” “You don't want spring water; you want to water it with your tears. It's the way they always do.” “Why, Mars Tom, I lay I kin raise one er dem mullen-stalks twyste wid spring water whiles another man's a start'n one wid tears.” “That ain't the idea. You got to do it with tears.” “She'll die on my han's, Mars Tom, she sholy will; kase I doan' skasely ever cry.” So Tom was stumped. But he studied it over, and then said Jim would have to worry along the best he could with an onion. He promised he would go to the nigger cabins and drop one, private, in Jim's coffee-pot, in the morning. Jim said he would “jis' 's soon have tobacker in his coffee;” and found so much fault with it, and with the work and bother of raising the mullen, and jews-harping the rats, and petting and flattering up the snakes and spiders and things, on top of all the other work he had to do on pens, and inscriptions, and journals, and things, which made it more trouble and worry and responsibility to be a prisoner than anything he ever undertook, that Tom most lost all patience with him; and said he was just loadened down with more gaudier chances than a prisoner ever had in the world to make a name for himself, and yet he didn't know enough to appreciate them, and they was just about wasted on him. So Jim he was sorry, and said he wouldn't behave so no more, and then me and Tom shoved for bed. CHAPTER XXXIX. IN the morning we went up to the village and bought a wire rat-trap and fetched it down, and unstopped the best rat-hole, and in about an hour we had fifteen of the bulliest kind of ones; and then we took it and put it in a safe place under Aunt Sally's bed. But while we was gone for spiders little Thomas Franklin Benjamin Jefferson Elexander Phelps found it there, and opened the door of it to see if the rats would come out, and they did; and Aunt Sally she come in, and when we got back she was a-standing on top of the bed raising Cain, and the rats was doing what they could to keep off the dull times for her. So she took and dusted us both with the hickry, and we was as much as two hours catching another fifteen or sixteen, drat that meddlesome cub, and they warn't the likeliest, nuther, because the first haul was the pick of the flock. I never see a likelier lot of rats than what that first haul was. We got a splendid stock of sorted spiders, and bugs, and frogs, and caterpillars, and one thing or another; and we like to got a hornet's nest, but we didn't. The family was at home. We didn't give it right up, but stayed with them as long as we could; because we allowed we'd tire them out or they'd got to tire us out, and they done it. Then we got allycumpain and rubbed on the places, and was pretty near all right again, but couldn't set down convenient. And so we went for the snakes, and grabbed a couple of dozen garters and house-snakes, and put them in a bag, and put it in our room, and by that time it was supper-time, and a rattling good honest day's work: and hungry?—oh, no, I reckon not! And there warn't a blessed snake up there when we went back—we didn't half tie the sack, and they worked out somehow, and left. But it didn't matter much, because they was still on the premises somewheres. So we judged we could get some of them again. No, there warn't no real scarcity of snakes about the house for a considerable spell. You'd see them dripping from the rafters and places every now and then; and they generly landed in your plate, or down the back of your neck, and most of the time where you didn't want them. Well, they was handsome and striped, and there warn't no harm in a million of them; but that never made no difference to Aunt Sally; she despised snakes, be the breed what they might, and she couldn't stand them no way you could fix it; and every time one of them flopped down on her, it didn't make no difference what she was doing, she would just lay that work down and light out. I never see such a woman. And you could hear her whoop to Jericho. You couldn't get her to take a-holt of one of them with the tongs. And if she turned over and found one in bed she would scramble out and lift a howl that you would think the house was afire. She disturbed the old man so that he said he could most wish there hadn't ever been no snakes created. Why, after every last snake had been gone clear out of the house for as much as a week Aunt Sally warn't over it yet; she warn't near over it; when she was setting thinking about something you could touch her on the back of her neck with a feather and she would jump right out of her stockings. It was very curious. But Tom said all women was just so. He said they was made that way for some reason or other. We got a licking every time one of our snakes come in her way, and she allowed these lickings warn't nothing to what she would do if we ever loaded up the place again with them. I didn't mind the lickings, because they didn't amount to nothing; but I minded the trouble we had to lay in another lot. But we got them laid in, and all the other things; and you never see a cabin as blithesome as Jim's was when they'd all swarm out for music and go for him. Jim didn't like the spiders, and the spiders didn't like Jim; and so they'd lay for him, and make it mighty warm for him. And he said that between the rats and the snakes and the grindstone there warn't no room in bed for him, skasely; and when there was, a body couldn't sleep, it was so lively, and it was always lively, he said, because they never all slept at one time, but took turn about, so when the snakes was asleep the rats was on deck, and when the rats turned in the snakes come on watch, so he always had one gang under him, in his way, and t'other gang having a circus over him, and if he got up to hunt a new place the spiders would take a chance at him as he crossed over. He said if he ever got out this time he wouldn't ever be a prisoner again, not for a salary. Well, by the end of three weeks everything was in pretty good shape. The shirt was sent in early, in a pie, and every time a rat bit Jim he would get up and write a little in his journal whilst the ink was fresh; the pens was made, the inscriptions and so on was all carved on the grindstone; the bed-leg was sawed in two, and we had et up the sawdust, and it give us a most amazing stomach-ache. We reckoned we was all going to die, but didn't. It was the most undigestible sawdust I ever see; and Tom said the same. But as I was saying, we'd got all the work done now, at last; and we was all pretty much fagged out, too, but mainly Jim. The old man had wrote a couple of times to the plantation below Orleans to come and get their runaway nigger, but hadn't got no answer, because there warn't no such plantation; so he allowed he would advertise Jim in the St. Louis and New Orleans papers; and when he mentioned the St. Louis ones it give me the cold shivers, and I see we hadn't no time to lose. So Tom said, now for the nonnamous letters. “What's them?” I says. “Warnings to the people that something is up. Sometimes it's done one way, sometimes another. But there's always somebody spying around that gives notice to the governor of the castle. When Louis XVI. was going to light out of the Tooleries, a servant-girl done it. It's a very good way, and so is the nonnamous letters. We'll use them both. And it's usual for the prisoner's mother to change clothes with him, and she stays in, and he slides out in her clothes. We'll do that, too.” “But looky here, Tom, what do we want to warn anybody for that something's up? Let them find it out for themselves—it's their lookout.” “Yes, I know; but you can't depend on them. It's the way they've acted from the very start—left us to do everything. They're so confiding and mullet-headed they don't take notice of nothing at all. So if we don't give them notice there won't be nobody nor nothing to interfere with us, and so after all our hard work and trouble this escape 'll go off perfectly flat; won't amount to nothing—won't be nothing to it.” “Well, as for me, Tom, that's the way I'd like.” “Shucks!” he says, and looked disgusted. So I says: “But I ain't going to make no complaint. Any way that suits you suits me. What you going to do about the servant-girl?” “You'll be her. You slide in, in the middle of the night, and hook that yaller girl's frock.” “Why, Tom, that 'll make trouble next morning; because, of course, she prob'bly hain't got any but that one.” “I know; but you don't want it but fifteen minutes, to carry the nonnamous letter and shove it under the front door.” “All right, then, I'll do it; but I could carry it just as handy in my own togs.” “You wouldn't look like a servant-girl then, would you?” “No, but there won't be nobody to see what I look like, anyway.” “That ain't got nothing to do with it. The thing for us to do is just to do our duty, and not worry about whether anybody sees us do it or not. Hain't you got no principle at all?” “All right, I ain't saying nothing; I'm the servant-girl. Who's Jim's mother?” “I'm his mother. I'll hook a gown from Aunt Sally.” “Well, then, you'll have to stay in the cabin when me and Jim leaves.” “Not much. I'll stuff Jim's clothes full of straw and lay it on his bed to represent his mother in disguise, and Jim 'll take the nigger woman's gown off of me and wear it, and we'll all evade together. When a prisoner of style escapes it's called an evasion. It's always called so when a king escapes, f'rinstance. And the same with a king's son; it don't make no difference whether he's a natural one or an unnatural one.” So Tom he wrote the nonnamous letter, and I smouched the yaller wench's frock that night, and put it on, and shoved it under the front door, the way Tom told me to. It said: Beware. Trouble is brewing. Keep a sharp lookout. Unknown Friend. Next night we stuck a picture, which Tom drawed in blood, of a skull and crossbones on the front door; and next night another one of a coffin on the back door. I never see a family in such a sweat. They couldn't a been worse scared if the place had a been full of ghosts laying for them behind everything and under the beds and shivering through the air. If a door banged, Aunt Sally she jumped and said “ouch!” if anything fell, she jumped and said “ouch!” if you happened to touch her, when she warn't noticing, she done the same; she couldn't face noway and be satisfied, because she allowed there was something behind her every time—so she was always a-whirling around sudden, and saying “ouch,” and before she'd got two-thirds around she'd whirl back again, and say it again; and she was afraid to go to bed, but she dasn't set up. So the thing was working very well, Tom said; he said he never see a thing work more satisfactory. He said it showed it was done right. So he said, now for the grand bulge! So the very next morning at the streak of dawn we got another letter ready, and was wondering what we better do with it, because we heard them say at supper they was going to have a nigger on watch at both doors all night. Tom he went down the lightning-rod to spy around; and the nigger at the back door was asleep, and he stuck it in the back of his neck and come back. This letter said: Don't betray me, I wish to be your friend. There is a desprate gang of cutthroats from over in the Indian Territory going to steal your runaway nigger to-night, and they have been trying to scare you so as you will stay in the house and not bother them. I am one of the gang, but have got religgion and wish to quit it and lead an honest life again, and will betray the helish design. They will sneak down from northards, along the fence, at midnight exact, with a false key, and go in the nigger's cabin to get him. I am to be off a piece and blow a tin horn if I see any danger; but stead of that I will baa like a sheep soon as they get in and not blow at all; then whilst they are getting his chains loose, you slip there and lock them in, and can kill them at your leasure. Don't do anything but just the way I am telling you, if you do they will suspicion something and raise whoop-jamboreehoo. I do not wish any reward but to know I have done the right thing. Unknown Friend. CHAPTER XL. WE was feeling pretty good after breakfast, and took my canoe and went over the river a-fishing, with a lunch, and had a good time, and took a look at the raft and found her all right, and got home late to supper, and found them in such a sweat and worry they didn't know which end they was standing on, and made us go right off to bed the minute we was done supper, and wouldn't tell us what the trouble was, and never let on a word about the new letter, but didn't need to, because we knowed as much about it as anybody did, and as soon as we was half up stairs and her back was turned we slid for the cellar cupboard and loaded up a good lunch and took it up to our room and went to bed, and got up about half-past eleven, and Tom put on Aunt Sally's dress that he stole and was going to start with the lunch, but says: “Where's the butter?” “I laid out a hunk of it,” I says, “on a piece of a corn-pone.” “Well, you left it laid out, then—it ain't here.” “We can get along without it,” I says. “We can get along with it, too,” he says; “just you slide down cellar and fetch it. And then mosey right down the lightning-rod and come along. I'll go and stuff the straw into Jim's clothes to represent his mother in disguise, and be ready to baa like a sheep and shove soon as you get there.” So out he went, and down cellar went I. The hunk of butter, big as a person's fist, was where I had left it, so I took up the slab of corn-pone with it on, and blowed out my light, and started up stairs very stealthy, and got up to the main floor all right, but here comes Aunt Sally with a candle, and I clapped the truck in my hat, and clapped my hat on my head, and the next second she see me; and she says: “You been down cellar?” “Yes'm.” “What you been doing down there?” “Noth'n.” “Noth'n!” “No'm.” “Well, then, what possessed you to go down there this time of night?” “I don't know 'm.” “You don't know? Don't answer me that way. Tom, I want to know what you been doing down there.” “I hain't been doing a single thing, Aunt Sally, I hope to gracious if I have.” I reckoned she'd let me go now, and as a generl thing she would; but I s'pose there was so many strange things going on she was just in a sweat about every little thing that warn't yard-stick straight; so she says, very decided: “You just march into that setting-room and stay there till I come. You been up to something you no business to, and I lay I'll find out what it is before I'M done with you.” So she went away as I opened the door and walked into the setting-room. My, but there was a crowd there! Fifteen farmers, and every one of them had a gun. I was most powerful sick, and slunk to a chair and set down. They was setting around, some of them talking a little, in a low voice, and all of them fidgety and uneasy, but trying to look like they warn't; but I knowed they was, because they was always taking off their hats, and putting them on, and scratching their heads, and changing their seats, and fumbling with their buttons. I warn't easy myself, but I didn't take my hat off, all the same. I did wish Aunt Sally would come, and get done with me, and lick me, if she wanted to, and let me get away and tell Tom how we'd overdone this thing, and what a thundering hornet's-nest we'd got ourselves into, so we could stop fooling around straight off, and clear out with Jim before these rips got out of patience and come for us. At last she come and begun to ask me questions, but I couldn't answer them straight, I didn't know which end of me was up; because these men was in such a fidget now that some was wanting to start right NOW and lay for them desperadoes, and saying it warn't but a few minutes to midnight; and others was trying to get them to hold on and wait for the sheep-signal; and here was Aunty pegging away at the questions, and me a-shaking all over and ready to sink down in my tracks I was that scared; and the place getting hotter and hotter, and the butter beginning to melt and run down my neck and behind my ears; and pretty soon, when one of them says, “I'M for going and getting in the cabin first and right now, and catching them when they come,” I most dropped; and a streak of butter come a-trickling down my forehead, and Aunt Sally she see it, and turns white as a sheet, and says: “For the land's sake, what is the matter with the child? He's got the brain-fever as shore as you're born, and they're oozing out!” And everybody runs to see, and she snatches off my hat, and out comes the bread and what was left of the butter, and she grabbed me, and hugged me, and says: “Oh, what a turn you did give me! and how glad and grateful I am it ain't no worse; for luck's against us, and it never rains but it pours, and when I see that truck I thought we'd lost you, for I knowed by the color and all it was just like your brains would be if—Dear, dear, whyd'nt you tell me that was what you'd been down there for, I wouldn't a cared. Now cler out to bed, and don't lemme see no more of you till morning!” I was up stairs in a second, and down the lightning-rod in another one, and shinning through the dark for the lean-to. I couldn't hardly get my words out, I was so anxious; but I told Tom as quick as I could we must jump for it now, and not a minute to lose—the house full of men, yonder, with guns! His eyes just blazed; and he says: “No!—is that so? ain't it bully! Why, Huck, if it was to do over again, I bet I could fetch two hundred! If we could put it off till—” “Hurry! Hurry!” I says. "Where's Jim?” “Right at your elbow; if you reach out your arm you can touch him. He's dressed, and everything's ready. Now we'll slide out and give the sheep-signal.” But then we heard the tramp of men coming to the door, and heard them begin to fumble with the pad-lock, and heard a man say: “I told you we'd be too soon; they haven't come—the door is locked. Here, I'll lock some of you into the cabin, and you lay for 'em in the dark and kill 'em when they come; and the rest scatter around a piece, and listen if you can hear 'em coming.” So in they come, but couldn't see us in the dark, and most trod on us whilst we was hustling to get under the bed. But we got under all right, and out through the hole, swift but soft—Jim first, me next, and Tom last, which was according to Tom's orders. Now we was in the lean-to, and heard trampings close by outside. So we crept to the door, and Tom stopped us there and put his eye to the crack, but couldn't make out nothing, it was so dark; and whispered and said he would listen for the steps to get further, and when he nudged us Jim must glide out first, and him last. So he set his ear to the crack and listened, and listened, and listened, and the steps a-scraping around out there all the time; and at last he nudged us, and we slid out, and stooped down, not breathing, and not making the least noise, and slipped stealthy towards the fence in Injun file, and got to it all right, and me and Jim over it; but Tom's britches catched fast on a splinter on the top rail, and then he hear the steps coming, so he had to pull loose, which snapped the splinter and made a noise; and as he dropped in our tracks and started somebody sings out: “Who's that? Answer, or I'll shoot!” But we didn't answer; we just unfurled our heels and shoved. Then there was a rush, and a Bang, Bang, Bang! and the bullets fairly whizzed around us! We heard them sing out: “Here they are! They've broke for the river! After 'em, boys, and turn loose the dogs!” So here they come, full tilt. We could hear them because they wore boots and yelled, but we didn't wear no boots and didn't yell. We was in the path to the mill; and when they got pretty close on to us we dodged into the bush and let them go by, and then dropped in behind them. They'd had all the dogs shut up, so they wouldn't scare off the robbers; but by this time somebody had let them loose, and here they come, making powwow enough for a million; but they was our dogs; so we stopped in our tracks till they catched up; and when they see it warn't nobody but us, and no excitement to offer them, they only just said howdy, and tore right ahead towards the shouting and clattering; and then we up-steam again, and whizzed along after them till we was nearly to the mill, and then struck up through the bush to where my canoe was tied, and hopped in and pulled for dear life towards the middle of the river, but didn't make no more noise than we was obleeged to. Then we struck out, easy and comfortable, for the island where my raft was; and we could hear them yelling and barking at each other all up and down the bank, till we was so far away the sounds got dim and died out. And when we stepped on to the raft I says: “Now, old Jim, you're a free man again, and I bet you won't ever be a slave no more.” “En a mighty good job it wuz, too, Huck. It 'uz planned beautiful, en it 'uz done beautiful; en dey ain't nobody kin git up a plan dat's mo' mixed-up en splendid den what dat one wuz.” We was all glad as we could be, but Tom was the gladdest of all because he had a bullet in the calf of his leg. When me and Jim heard that we didn't feel so brash as what we did before. It was hurting him considerable, and bleeding; so we laid him in the wigwam and tore up one of the duke's shirts for to bandage him, but he says: “Gimme the rags; I can do it myself. Don't stop now; don't fool around here, and the evasion booming along so handsome; man the sweeps, and set her loose! Boys, we done it elegant!—'deed we did. I wish we'd a had the handling of Louis XVI., there wouldn't a been no 'Son of Saint Louis, ascend to heaven!' wrote down in his biography; no, sir, we'd a whooped him over the border—that's what we'd a done with him—and done it just as slick as nothing at all, too. Man the sweeps—man the sweeps!” But me and Jim was consulting—and thinking. And after we'd thought a minute, I says: “Say it, Jim.” So he says: “Well, den, dis is de way it look to me, Huck. Ef it wuz him dat 'uz bein' sot free, en one er de boys wuz to git shot, would he say, 'Go on en save me, nemmine 'bout a doctor f'r to save dis one?' Is dat like Mars Tom Sawyer? Would he say dat? You bet he wouldn't! well, den, is Jim gywne to say it? No, sah—I doan' budge a step out'n dis place 'dout a doctor, not if it's forty year!” I knowed he was white inside, and I reckoned he'd say what he did say—so it was all right now, and I told Tom I was a-going for a doctor. He raised considerable row about it, but me and Jim stuck to it and wouldn't budge; so he was for crawling out and setting the raft loose himself; but we wouldn't let him. Then he give us a piece of his mind, but it didn't do no good. So when he sees me getting the canoe ready, he says: “Well, then, if you're bound to go, I'll tell you the way to do when you get to the village. Shut the door and blindfold the doctor tight and fast, and make him swear to be silent as the grave, and put a purse full of gold in his hand, and then take and lead him all around the back alleys and everywheres in the dark, and then fetch him here in the canoe, in a roundabout way amongst the islands, and search him and take his chalk away from him, and don't give it back to him till you get him back to the village, or else he will chalk this raft so he can find it again. It's the way they all do.” So I said I would, and left, and Jim was to hide in the woods when he see the doctor coming till he was gone again. CHAPTER XLI. THE doctor was an old man; a very nice, kind-looking old man when I got him up. I told him me and my brother was over on Spanish Island hunting yesterday afternoon, and camped on a piece of a raft we found, and about midnight he must a kicked his gun in his dreams, for it went off and shot him in the leg, and we wanted him to go over there and fix it and not say nothing about it, nor let anybody know, because we wanted to come home this evening and surprise the folks. “Who is your folks?” he says. “The Phelpses, down yonder.” “Oh,” he says. And after a minute, he says: “How'd you say he got shot?” “He had a dream,” I says, “and it shot him.” “Singular dream,” he says. So he lit up his lantern, and got his saddle-bags, and we started. But when he sees the canoe he didn't like the look of her—said she was big enough for one, but didn't look pretty safe for two. I says: “Oh, you needn't be afeard, sir, she carried the three of us easy enough.” “What three?” “Why, me and Sid, and—and—and the guns; that's what I mean.” “Oh,” he says. But he put his foot on the gunnel and rocked her, and shook his head, and said he reckoned he'd look around for a bigger one. But they was all locked and chained; so he took my canoe, and said for me to wait till he come back, or I could hunt around further, or maybe I better go down home and get them ready for the surprise if I wanted to. But I said I didn't; so I told him just how to find the raft, and then he started. I struck an idea pretty soon. I says to myself, spos'n he can't fix that leg just in three shakes of a sheep's tail, as the saying is? spos'n it takes him three or four days? What are we going to do?—lay around there till he lets the cat out of the bag? No, sir; I know what I'll do. I'll wait, and when he comes back if he says he's got to go any more I'll get down there, too, if I swim; and we'll take and tie him, and keep him, and shove out down the river; and when Tom's done with him we'll give him what it's worth, or all we got, and then let him get ashore. So then I crept into a lumber-pile to get some sleep; and next time I waked up the sun was away up over my head! I shot out and went for the doctor's house, but they told me he'd gone away in the night some time or other, and warn't back yet. Well, thinks I, that looks powerful bad for Tom, and I'll dig out for the island right off. So away I shoved, and turned the corner, and nearly rammed my head into Uncle Silas's stomach! He says: “Why, Tom! Where you been all this time, you rascal?” “I hain't been nowheres,” I says, “only just hunting for the runaway nigger—me and Sid.” “Why, where ever did you go?” he says. "Your aunt's been mighty uneasy.” “She needn't,” I says, “because we was all right. We followed the men and the dogs, but they outrun us, and we lost them; but we thought we heard them on the water, so we got a canoe and took out after them and crossed over, but couldn't find nothing of them; so we cruised along up-shore till we got kind of tired and beat out; and tied up the canoe and went to sleep, and never waked up till about an hour ago; then we paddled over here to hear the news, and Sid's at the post-office to see what he can hear, and I'm a-branching out to get something to eat for us, and then we're going home.” So then we went to the post-office to get “Sid”; but just as I suspicioned, he warn't there; so the old man he got a letter out of the office, and we waited awhile longer, but Sid didn't come; so the old man said, come along, let Sid foot it home, or canoe it, when he got done fooling around—but we would ride. I couldn't get him to let me stay and wait for Sid; and he said there warn't no use in it, and I must come along, and let Aunt Sally see we was all right. When we got home Aunt Sally was that glad to see me she laughed and cried both, and hugged me, and give me one of them lickings of hern that don't amount to shucks, and said she'd serve Sid the same when he come. And the place was plum full of farmers and farmers' wives, to dinner; and such another clack a body never heard. Old Mrs. Hotchkiss was the worst; her tongue was a-going all the time. She says: “Well, Sister Phelps, I've ransacked that-air cabin over, an' I b'lieve the nigger was crazy. I says to Sister Damrell—didn't I, Sister Damrell?—s'I, he's crazy, s'I—them's the very words I said. You all hearn me: he's crazy, s'I; everything shows it, s'I. Look at that-air grindstone, s'I; want to tell me't any cretur 't's in his right mind 's a goin' to scrabble all them crazy things onto a grindstone, s'I? Here sich 'n' sich a person busted his heart; 'n' here so 'n' so pegged along for thirty-seven year, 'n' all that—natcherl son o' Louis somebody, 'n' sich everlast'n rubbage. He's plumb crazy, s'I; it's what I says in the fust place, it's what I says in the middle, 'n' it's what I says last 'n' all the time—the nigger's crazy—crazy 's Nebokoodneezer, s'I.” “An' look at that-air ladder made out'n rags, Sister Hotchkiss,” says old Mrs. Damrell; “what in the name o' goodness could he ever want of—” “The very words I was a-sayin' no longer ago th'n this minute to Sister Utterback, 'n' she'll tell you so herself. Sh-she, look at that-air rag ladder, sh-she; 'n' s'I, yes, look at it, s'I—what could he a-wanted of it, s'I. Sh-she, Sister Hotchkiss, sh-she—” “But how in the nation'd they ever git that grindstone in there, anyway? 'n' who dug that-air hole? 'n' who—” “My very words, Brer Penrod! I was a-sayin'—pass that-air sasser o' m'lasses, won't ye?—I was a-sayin' to Sister Dunlap, jist this minute, how did they git that grindstone in there, s'I. Without help, mind you—'thout help! that's wher 'tis. Don't tell me, s'I; there wuz help, s'I; 'n' ther' wuz a plenty help, too, s'I; ther's ben a dozen a-helpin' that nigger, 'n' I lay I'd skin every last nigger on this place but I'd find out who done it, s'I; 'n' moreover, s'I—” “A dozen says you!—forty couldn't a done every thing that's been done. Look at them case-knife saws and things, how tedious they've been made; look at that bed-leg sawed off with 'm, a week's work for six men; look at that nigger made out'n straw on the bed; and look at—” “You may well say it, Brer Hightower! It's jist as I was a-sayin' to Brer Phelps, his own self. S'e, what do you think of it, Sister Hotchkiss, s'e? Think o' what, Brer Phelps, s'I? Think o' that bed-leg sawed off that a way, s'e? think of it, s'I? I lay it never sawed itself off, s'I—somebody sawed it, s'I; that's my opinion, take it or leave it, it mayn't be no 'count, s'I, but sich as 't is, it's my opinion, s'I, 'n' if any body k'n start a better one, s'I, let him do it, s'I, that's all. I says to Sister Dunlap, s'I—” “Why, dog my cats, they must a ben a house-full o' niggers in there every night for four weeks to a done all that work, Sister Phelps. Look at that shirt—every last inch of it kivered over with secret African writ'n done with blood! Must a ben a raft uv 'm at it right along, all the time, amost. Why, I'd give two dollars to have it read to me; 'n' as for the niggers that wrote it, I 'low I'd take 'n' lash 'm t'll—” “People to help him, Brother Marples! Well, I reckon you'd think so if you'd a been in this house for a while back. Why, they've stole everything they could lay their hands on—and we a-watching all the time, mind you. They stole that shirt right off o' the line! and as for that sheet they made the rag ladder out of, ther' ain't no telling how many times they didn't steal that; and flour, and candles, and candlesticks, and spoons, and the old warming-pan, and most a thousand things that I disremember now, and my new calico dress; and me and Silas and my Sid and Tom on the constant watch day and night, as I was a-telling you, and not a one of us could catch hide nor hair nor sight nor sound of them; and here at the last minute, lo and behold you, they slides right in under our noses and fools us, and not only fools us but the Injun Territory robbers too, and actuly gets away with that nigger safe and sound, and that with sixteen men and twenty-two dogs right on their very heels at that very time! I tell you, it just bangs anything I ever heard of. Why, sperits couldn't a done better and been no smarter. And I reckon they must a been sperits—because, you know our dogs, and ther' ain't no better; well, them dogs never even got on the track of 'm once! You explain that to me if you can!—any of you!” “Well, it does beat—” “Laws alive, I never—” “So help me, I wouldn't a be—” “House-thieves as well as—” “Goodnessgracioussakes, I'd a ben afeard to live in sich a—” “'Fraid to live!—why, I was that scared I dasn't hardly go to bed, or get up, or lay down, or set down, Sister Ridgeway. Why, they'd steal the very—why, goodness sakes, you can guess what kind of a fluster I was in by the time midnight come last night. I hope to gracious if I warn't afraid they'd steal some o' the family! I was just to that pass I didn't have no reasoning faculties no more. It looks foolish enough now, in the daytime; but I says to myself, there's my two poor boys asleep, 'way up stairs in that lonesome room, and I declare to goodness I was that uneasy 't I crep' up there and locked 'em in! I did. And anybody would. Because, you know, when you get scared that way, and it keeps running on, and getting worse and worse all the time, and your wits gets to addling, and you get to doing all sorts o' wild things, and by and by you think to yourself, spos'n I was a boy, and was away up there, and the door ain't locked, and you—” She stopped, looking kind of wondering, and then she turned her head around slow, and when her eye lit on me—I got up and took a walk. Says I to myself, I can explain better how we come to not be in that room this morning if I go out to one side and study over it a little. So I done it. But I dasn't go fur, or she'd a sent for me. And when it was late in the day the people all went, and then I come in and told her the noise and shooting waked up me and “Sid,” and the door was locked, and we wanted to see the fun, so we went down the lightning-rod, and both of us got hurt a little, and we didn't never want to try that no more. And then I went on and told her all what I told Uncle Silas before; and then she said she'd forgive us, and maybe it was all right enough anyway, and about what a body might expect of boys, for all boys was a pretty harum-scarum lot as fur as she could see; and so, as long as no harm hadn't come of it, she judged she better put in her time being grateful we was alive and well and she had us still, stead of fretting over what was past and done. So then she kissed me, and patted me on the head, and dropped into a kind of a brown study; and pretty soon jumps up, and says: “Why, lawsamercy, it's most night, and Sid not come yet! What has become of that boy?” I see my chance; so I skips up and says: “I'll run right up to town and get him,” I says. “No you won't,” she says. "You'll stay right wher' you are; one's enough to be lost at a time. If he ain't here to supper, your uncle 'll go.” Well, he warn't there to supper; so right after supper uncle went. He come back about ten a little bit uneasy; hadn't run across Tom's track. Aunt Sally was a good deal uneasy; but Uncle Silas he said there warn't no occasion to be—boys will be boys, he said, and you'll see this one turn up in the morning all sound and right. So she had to be satisfied. But she said she'd set up for him a while anyway, and keep a light burning so he could see it. And then when I went up to bed she come up with me and fetched her candle, and tucked me in, and mothered me so good I felt mean, and like I couldn't look her in the face; and she set down on the bed and talked with me a long time, and said what a splendid boy Sid was, and didn't seem to want to ever stop talking about him; and kept asking me every now and then if I reckoned he could a got lost, or hurt, or maybe drownded, and might be laying at this minute somewheres suffering or dead, and she not by him to help him, and so the tears would drip down silent, and I would tell her that Sid was all right, and would be home in the morning, sure; and she would squeeze my hand, or maybe kiss me, and tell me to say it again, and keep on saying it, because it done her good, and she was in so much trouble. And when she was going away she looked down in my eyes so steady and gentle, and says: “The door ain't going to be locked, Tom, and there's the window and the rod; but you'll be good, won't you? And you won't go? For my sake.” Laws knows I wanted to go bad enough to see about Tom, and was all intending to go; but after that I wouldn't a went, not for kingdoms. But she was on my mind and Tom was on my mind, so I slept very restless. And twice I went down the rod away in the night, and slipped around front, and see her setting there by her candle in the window with her eyes towards the road and the tears in them; and I wished I could do something for her, but I couldn't, only to swear that I wouldn't never do nothing to grieve her any more. And the third time I waked up at dawn, and slid down, and she was there yet, and her candle was most out, and her old gray head was resting on her hand, and she was asleep. CHAPTER XLII. THE old man was uptown again before breakfast, but couldn't get no track of Tom; and both of them set at the table thinking, and not saying nothing, and looking mournful, and their coffee getting cold, and not eating anything. And by and by the old man says: “Did I give you the letter?” “What letter?” “The one I got yesterday out of the post-office.” “No, you didn't give me no letter.” “Well, I must a forgot it.” So he rummaged his pockets, and then went off somewheres where he had laid it down, and fetched it, and give it to her. She says: “Why, it's from St. Petersburg—it's from Sis.” I allowed another walk would do me good; but I couldn't stir. But before she could break it open she dropped it and run—for she see something. And so did I. It was Tom Sawyer on a mattress; and that old doctor; and Jim, in her calico dress, with his hands tied behind him; and a lot of people. I hid the letter behind the first thing that come handy, and rushed. She flung herself at Tom, crying, and says: “Oh, he's dead, he's dead, I know he's dead!” And Tom he turned his head a little, and muttered something or other, which showed he warn't in his right mind; then she flung up her hands, and says: “He's alive, thank God! And that's enough!” and she snatched a kiss of him, and flew for the house to get the bed ready, and scattering orders right and left at the niggers and everybody else, as fast as her tongue could go, every jump of the way. I followed the men to see what they was going to do with Jim; and the old doctor and Uncle Silas followed after Tom into the house. The men was very huffy, and some of them wanted to hang Jim for an example to all the other niggers around there, so they wouldn't be trying to run away like Jim done, and making such a raft of trouble, and keeping a whole family scared most to death for days and nights. But the others said, don't do it, it wouldn't answer at all; he ain't our nigger, and his owner would turn up and make us pay for him, sure. So that cooled them down a little, because the people that's always the most anxious for to hang a nigger that hain't done just right is always the very ones that ain't the most anxious to pay for him when they've got their satisfaction out of him. They cussed Jim considerble, though, and give him a cuff or two side the head once in a while, but Jim never said nothing, and he never let on to know me, and they took him to the same cabin, and put his own clothes on him, and chained him again, and not to no bed-leg this time, but to a big staple drove into the bottom log, and chained his hands, too, and both legs, and said he warn't to have nothing but bread and water to eat after this till his owner come, or he was sold at auction because he didn't come in a certain length of time, and filled up our hole, and said a couple of farmers with guns must stand watch around about the cabin every night, and a bulldog tied to the door in the daytime; and about this time they was through with the job and was tapering off with a kind of generl good-bye cussing, and then the old doctor comes and takes a look, and says: “Don't be no rougher on him than you're obleeged to, because he ain't a bad nigger. When I got to where I found the boy I see I couldn't cut the bullet out without some help, and he warn't in no condition for me to leave to go and get help; and he got a little worse and a little worse, and after a long time he went out of his head, and wouldn't let me come a-nigh him any more, and said if I chalked his raft he'd kill me, and no end of wild foolishness like that, and I see I couldn't do anything at all with him; so I says, I got to have help somehow; and the minute I says it out crawls this nigger from somewheres and says he'll help, and he done it, too, and done it very well. Of course I judged he must be a runaway nigger, and there I was! and there I had to stick right straight along all the rest of the day and all night. It was a fix, I tell you! I had a couple of patients with the chills, and of course I'd of liked to run up to town and see them, but I dasn't, because the nigger might get away, and then I'd be to blame; and yet never a skiff come close enough for me to hail. So there I had to stick plumb until daylight this morning; and I never see a nigger that was a better nuss or faithfuller, and yet he was risking his freedom to do it, and was all tired out, too, and I see plain enough he'd been worked main hard lately. I liked the nigger for that; I tell you, gentlemen, a nigger like that is worth a thousand dollars—and kind treatment, too. I had everything I needed, and the boy was doing as well there as he would a done at home—better, maybe, because it was so quiet; but there I was, with both of 'm on my hands, and there I had to stick till about dawn this morning; then some men in a skiff come by, and as good luck would have it the nigger was setting by the pallet with his head propped on his knees sound asleep; so I motioned them in quiet, and they slipped up on him and grabbed him and tied him before he knowed what he was about, and we never had no trouble. And the boy being in a kind of a flighty sleep, too, we muffled the oars and hitched the raft on, and towed her over very nice and quiet, and the nigger never made the least row nor said a word from the start. He ain't no bad nigger, gentlemen; that's what I think about him.” Somebody says: “Well, it sounds very good, doctor, I'm obleeged to say.” Then the others softened up a little, too, and I was mighty thankful to that old doctor for doing Jim that good turn; and I was glad it was according to my judgment of him, too; because I thought he had a good heart in him and was a good man the first time I see him. Then they all agreed that Jim had acted very well, and was deserving to have some notice took of it, and reward. So every one of them promised, right out and hearty, that they wouldn't cuss him no more. Then they come out and locked him up. I hoped they was going to say he could have one or two of the chains took off, because they was rotten heavy, or could have meat and greens with his bread and water; but they didn't think of it, and I reckoned it warn't best for me to mix in, but I judged I'd get the doctor's yarn to Aunt Sally somehow or other as soon as I'd got through the breakers that was laying just ahead of me—explanations, I mean, of how I forgot to mention about Sid being shot when I was telling how him and me put in that dratted night paddling around hunting the runaway nigger. But I had plenty time. Aunt Sally she stuck to the sick-room all day and all night, and every time I see Uncle Silas mooning around I dodged him. Next morning I heard Tom was a good deal better, and they said Aunt Sally was gone to get a nap. So I slips to the sick-room, and if I found him awake I reckoned we could put up a yarn for the family that would wash. But he was sleeping, and sleeping very peaceful, too; and pale, not fire-faced the way he was when he come. So I set down and laid for him to wake. In about half an hour Aunt Sally comes gliding in, and there I was, up a stump again! She motioned me to be still, and set down by me, and begun to whisper, and said we could all be joyful now, because all the symptoms was first-rate, and he'd been sleeping like that for ever so long, and looking better and peacefuller all the time, and ten to one he'd wake up in his right mind. So we set there watching, and by and by he stirs a bit, and opened his eyes very natural, and takes a look, and says: “Hello!—why, I'm at home! How's that? Where's the raft?” “It's all right,” I says. “And Jim?” “The same,” I says, but couldn't say it pretty brash. But he never noticed, but says: “Good! Splendid! Now we're all right and safe! Did you tell Aunty?” I was going to say yes; but she chipped in and says: "About what, Sid?” “Why, about the way the whole thing was done.” “What whole thing?” “Why, the whole thing. There ain't but one; how we set the runaway nigger free—me and Tom.” “Good land! Set the run—What is the child talking about! Dear, dear, out of his head again!” “No, I ain't out of my head; I know all what I'm talking about. We did set him free—me and Tom. We laid out to do it, and we done it. And we done it elegant, too.” He'd got a start, and she never checked him up, just set and stared and stared, and let him clip along, and I see it warn't no use for me to put in. "Why, Aunty, it cost us a power of work—weeks of it—hours and hours, every night, whilst you was all asleep. And we had to steal candles, and the sheet, and the shirt, and your dress, and spoons, and tin plates, and case-knives, and the warming-pan, and the grindstone, and flour, and just no end of things, and you can't think what work it was to make the saws, and pens, and inscriptions, and one thing or another, and you can't think half the fun it was. And we had to make up the pictures of coffins and things, and nonnamous letters from the robbers, and get up and down the lightning-rod, and dig the hole into the cabin, and made the rope ladder and send it in cooked up in a pie, and send in spoons and things to work with in your apron pocket—” “Mercy sakes!” “—and load up the cabin with rats and snakes and so on, for company for Jim; and then you kept Tom here so long with the butter in his hat that you come near spiling the whole business, because the men come before we was out of the cabin, and we had to rush, and they heard us and let drive at us, and I got my share, and we dodged out of the path and let them go by, and when the dogs come they warn't interested in us, but went for the most noise, and we got our canoe, and made for the raft, and was all safe, and Jim was a free man, and we done it all by ourselves, and wasn't it bully, Aunty!” “Well, I never heard the likes of it in all my born days! So it was you, you little rapscallions, that's been making all this trouble, and turned everybody's wits clean inside out and scared us all most to death. I've as good a notion as ever I had in my life to take it out o' you this very minute. To think, here I've been, night after night, a—you just get well once, you young scamp, and I lay I'll tan the Old Harry out o' both o' ye!” But Tom, he was so proud and joyful, he just couldn't hold in, and his tongue just went it—she a-chipping in, and spitting fire all along, and both of them going it at once, like a cat convention; and she says: “Well, you get all the enjoyment you can out of it now, for mind I tell you if I catch you meddling with him again—” “Meddling with who?” Tom says, dropping his smile and looking surprised. “With who? Why, the runaway nigger, of course. Who'd you reckon?” Tom looks at me very grave, and says: “Tom, didn't you just tell me he was all right? Hasn't he got away?” “Him?” says Aunt Sally; “the runaway nigger? 'Deed he hasn't. They've got him back, safe and sound, and he's in that cabin again, on bread and water, and loaded down with chains, till he's claimed or sold!” Tom rose square up in bed, with his eye hot, and his nostrils opening and shutting like gills, and sings out to me: “They hain't no right to shut him up! SHOVE!—and don't you lose a minute. Turn him loose! he ain't no slave; he's as free as any cretur that walks this earth!” “What does the child mean?” “I mean every word I say, Aunt Sally, and if somebody don't go, I'll go. I've knowed him all his life, and so has Tom, there. Old Miss Watson died two months ago, and she was ashamed she ever was going to sell him down the river, and said so; and she set him free in her will.” “Then what on earth did you want to set him free for, seeing he was already free?” “Well, that is a question, I must say; and just like women! Why, I wanted the adventure of it; and I'd a waded neck-deep in blood to—goodness alive, Aunt Polly!” If she warn't standing right there, just inside the door, looking as sweet and contented as an angel half full of pie, I wish I may never! Aunt Sally jumped for her, and most hugged the head off of her, and cried over her, and I found a good enough place for me under the bed, for it was getting pretty sultry for us, seemed to me. And I peeped out, and in a little while Tom's Aunt Polly shook herself loose and stood there looking across at Tom over her spectacles—kind of grinding him into the earth, you know. And then she says: “Yes, you better turn y'r head away—I would if I was you, Tom.” “Oh, deary me!” says Aunt Sally; “Is he changed so? Why, that ain't Tom, it's Sid; Tom's—Tom's—why, where is Tom? He was here a minute ago.” “You mean where's Huck Finn—that's what you mean! I reckon I hain't raised such a scamp as my Tom all these years not to know him when I see him. That would be a pretty howdy-do. Come out from under that bed, Huck Finn.” So I done it. But not feeling brash. Aunt Sally she was one of the mixed-upest-looking persons I ever see—except one, and that was Uncle Silas, when he come in and they told it all to him. It kind of made him drunk, as you may say, and he didn't know nothing at all the rest of the day, and preached a prayer-meeting sermon that night that gave him a rattling ruputation, because the oldest man in the world couldn't a understood it. So Tom's Aunt Polly, she told all about who I was, and what; and I had to up and tell how I was in such a tight place that when Mrs. Phelps took me for Tom Sawyer—she chipped in and says, “Oh, go on and call me Aunt Sally, I'm used to it now, and 'tain't no need to change”—that when Aunt Sally took me for Tom Sawyer I had to stand it—there warn't no other way, and I knowed he wouldn't mind, because it would be nuts for him, being a mystery, and he'd make an adventure out of it, and be perfectly satisfied. And so it turned out, and he let on to be Sid, and made things as soft as he could for me. And his Aunt Polly she said Tom was right about old Miss Watson setting Jim free in her will; and so, sure enough, Tom Sawyer had gone and took all that trouble and bother to set a free nigger free! and I couldn't ever understand before, until that minute and that talk, how he could help a body set a nigger free with his bringing-up. Well, Aunt Polly she said that when Aunt Sally wrote to her that Tom and Sid had come all right and safe, she says to herself: “Look at that, now! I might have expected it, letting him go off that way without anybody to watch him. So now I got to go and trapse all the way down the river, eleven hundred mile, and find out what that creetur's up to this time, as long as I couldn't seem to get any answer out of you about it.” “Why, I never heard nothing from you,” says Aunt Sally. “Well, I wonder! Why, I wrote you twice to ask you what you could mean by Sid being here.” “Well, I never got 'em, Sis.” Aunt Polly she turns around slow and severe, and says: “You, Tom!” “Well—what?” he says, kind of pettish. “Don't you what me, you impudent thing—hand out them letters.” “What letters?” “Them letters. I be bound, if I have to take a-holt of you I'll—” “They're in the trunk. There, now. And they're just the same as they was when I got them out of the office. I hain't looked into them, I hain't touched them. But I knowed they'd make trouble, and I thought if you warn't in no hurry, I'd—” “Well, you do need skinning, there ain't no mistake about it. And I wrote another one to tell you I was coming; and I s'pose he—” “No, it come yesterday; I hain't read it yet, but it's all right, I've got that one.” I wanted to offer to bet two dollars she hadn't, but I reckoned maybe it was just as safe to not to. So I never said nothing. CHAPTER THE LAST THE first time I catched Tom private I asked him what was his idea, time of the evasion?—what it was he'd planned to do if the evasion worked all right and he managed to set a nigger free that was already free before? And he said, what he had planned in his head from the start, if we got Jim out all safe, was for us to run him down the river on the raft, and have adventures plumb to the mouth of the river, and then tell him about his being free, and take him back up home on a steamboat, in style, and pay him for his lost time, and write word ahead and get out all the niggers around, and have them waltz him into town with a torchlight procession and a brass-band, and then he would be a hero, and so would we. But I reckoned it was about as well the way it was. We had Jim out of the chains in no time, and when Aunt Polly and Uncle Silas and Aunt Sally found out how good he helped the doctor nurse Tom, they made a heap of fuss over him, and fixed him up prime, and give him all he wanted to eat, and a good time, and nothing to do. And we had him up to the sick-room, and had a high talk; and Tom give Jim forty dollars for being prisoner for us so patient, and doing it up so good, and Jim was pleased most to death, and busted out, and says: “Dah, now, Huck, what I tell you?—what I tell you up dah on Jackson islan'? I tole you I got a hairy breas', en what's de sign un it; en I tole you I ben rich wunst, en gwineter to be rich agin; en it's come true; en heah she is! dah, now! doan' talk to me—signs is signs, mine I tell you; en I knowed jis' 's well 'at I 'uz gwineter be rich agin as I's a-stannin' heah dis minute!” And then Tom he talked along and talked along, and says, le's all three slide out of here one of these nights and get an outfit, and go for howling adventures amongst the Injuns, over in the Territory, for a couple of weeks or two; and I says, all right, that suits me, but I ain't got no money for to buy the outfit, and I reckon I couldn't get none from home, because it's likely pap's been back before now, and got it all away from Judge Thatcher and drunk it up. “No, he hain't,” Tom says; “it's all there yet—six thousand dollars and more; and your pap hain't ever been back since. Hadn't when I come away, anyhow.” Jim says, kind of solemn: “He ain't a-comin' back no mo', Huck.” I says: “Why, Jim?” “Nemmine why, Huck—but he ain't comin' back no mo.” But I kept at him; so at last he says: “Doan' you 'member de house dat was float'n down de river, en dey wuz a man in dah, kivered up, en I went in en unkivered him and didn' let you come in? Well, den, you kin git yo' money when you wants it, kase dat wuz him.” Tom's most well now, and got his bullet around his neck on a watch-guard for a watch, and is always seeing what time it is, and so there ain't nothing more to write about, and I am rotten glad of it, because if I'd a knowed what a trouble it was to make a book I wouldn't a tackled it, and ain't a-going to no more. But I reckon I got to light out for the Territory ahead of the rest, because Aunt Sally she's going to adopt me and sivilize me, and I can't stand it. I been there before. THE END. YOURS TRULY, HUCK FINN. 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Huck feels guilty about taking the money, so he puts the money in the coffin to make himself feel better about lying.
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educatorinnovator.org educatorinnovator.org
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direc-tional motivation (the desire to justify conclusions that align with priorbeliefs)
I definitely agree that everyone to some extent has directional motivation. Given the many different media outlets that exist, it comes as no surprise that many of these outlets are biased and align with certain political beliefs or values. While we do have to acknowledge this, it is important for both ourselves and for educators to teach students ways to overcome this directional motivation. All individuals should have both values and beliefs that originate from logic, evidence-based claims. Further, we need to teach our students how to evaluate information being shared, and whether such information is credible and accurate or not. If we can teach our students these skills, then the future generations may be more inclined to think critically and logically about the civic issues that are at stake.
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s18.pdarrington.net s18.pdarrington.net
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Visual Mode The visual mode refers to the use of images and other characteris-tics that readers see. Billboards, flyers, television, Web sites, lighted advertising displays, even grocery store shelves bombard us with visual information in an effort to attract our attention. We can u-;e this mode to communicate representations of how something look~ or how someone is feeling, to instruct, to persuade, and to entertain, among other things. ·1 he visual mode includes: • color • layout • style • size • perspective
When writing blog posts responding to the AIDS quilt panels we can think about how images can be used in an effective way and how the layout of our posts can effect the way the reader may interpret our work. The NBC article is all about interpreting a visual. Based on it's color, shape, and cultural significance and discusses why people love it or hate it. Perspective has a lot to do with this. A CIS woman and a trans woman could have different views on it. Not to say one will definitely love it or hate it, but their views could differ. Even the article itself, while trying to remain unbiased, includes quotes that could sway the reader to believe that the creator had no intention of her hats to exclude anyone. Meanwhile another article is very biased into why the pink pussy hats are problematic for feminism.
https://www.freep.com/story/news/2018/01/10/pink-pussyhats-feminists-hats-womens-march/1013630001/
When we peer reviewed our last primary source descriptions, different people had different suggestions as to what to add or take away. We can keep this in mind when writing, that other perspectives are useful to have.
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edu307class.networkedlearningcollaborative.com edu307class.networkedlearningcollaborative.com
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nd, we might consider how to extend and expand our theory of the literary under standing of young children to include these types of response. They may act as powerful entr?es (for at least some children) to a more complete, more textured, and richer understanding of sto ries and how they work.
I think by having children communicate expressively about the story is a great way to learn and understand how stories work. By starting these lessons in kindergarten, once students get up to higher reading levels they might be able to grasp more literary elements faster.
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Where do we find ourselves if now we think one step further regarding what enframing itself actually is? It is nothing technological, nothing on the order of a machine. It is the way in which the actual reveals itself as standing-reserve. Again we ask: Does such revealing happen somewhere beyond all human doing? No. But neither does it happen exclusively in man, or definitively through man.
Technology has become a way in which a man becomes human. What separates us from other species is our intelligence and ability to make and create something even smarter than us. It is frightening to think we can be overpowered by what we control now but how about if that time actually comes? What if the sci-fi films regarding technology ruling over the world becomes a reality? What if humans become extinct because technology is far more powerful and lives longer than us mortal humans? Not only do they live but they exist longer. Is existence relating to a heartbeat with DNA or the capacity to have enough intelligence in which you do not need to have such heartbeat and DNA to function? There is so much a human mind is capable of creating that it becomes a terrifying reality to think that we may be controlled by what we control now.
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keywords.nyupress.org keywords.nyupress.org
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We may live in a digital age, and the privileged among us might feel closely connected to our digital devices, but the sensations we feel as we touch our keyboards and screens are analog feelings, rich in continuous input and gradations of the sensory. We must remember that the digital is embedded in an analog world even as it increasingly shapes what is possible within that world
I also think it is worth noting here that digital affects what happens in the analog/real world. What is written, posted, or viewed online can affect the real-life experience of the writer, poster, or viewer. Interactions between two parties online can directly affect how they interact in the real realm.
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students
I think the most valuable thing that an academic institution can do is to provide students with a relevant experience in their academic pursuit. It seems to me that this debate often boils down as an “either or” sort of option. Either we have good academic core courses or we have students who are trained. I believe that the answer should be formed as an “and”. By taking the curriculum that is required to provide for a complete education, (by this I mean an accredited Associate’s degree) and making it relevant to what the student is learning you can have both academic quality and career preparation. In reading our case study number 2 Hidden Stream Community College has it right. The students in the welding program are not there to learn how to write poetry. They are there to get the industry knowledge, which will lead to their employment. As part of their journey, they are learning relevant skills in their general education courses, which may resonate with them while they are studying the things they want to get a job. This should help pique the students’ interest, which may help keep them engaged in the institution
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does it work?" The second is, in the broadest sense, moral: "\44ratkind of a guv inhabits this poem? \{4rat is his notion of the goodlife or the good place? His notion of the trvil One? \\4rat does heconceal from the reader? \,\hat does he conceal even from him-self?" [so-st].Like any poet, Auden knor,l's that the second question cannot be re-sponded to correctly until the first has been ansu'ered. It is the rvorkingsof the verbal construct that give evidence of the moral stance of the poet.Auden here separates the technical from the moral, and perhaps believesthat the answer about the "verbal contraption" must be distinct from theanswer about personaliq,, ethics, and u,hat u'e s'ould nou, call "uncon-scious" and "deconstructive" moments in the poem. I believe that thedeepest insights into the moral u'orld of the poem, and into its construc-tive and deconstructive energies, come preciselv from understanding it asa contraption made of "words," by which I mean not onlv the semanticunits we call "words" but all the langpage games in u'hich u'ords can par-ticipate. Because many essays on the sonnets attempt moral and ethicaldiscussion without any close understanding of holv the poems are put to-gether, I have emphasized in this Commentan, the total "contraption-ness" of any given sonnet as the first necessary level of understanding. Ihope that my comments on the famous "moral" sonnets (such as 66,94,116, 129) will not disappoint readers u.ho are looking for Shakespeare's"notion of the good life . . . the Evil One" and so on. As to u'hat Shake-speare may conceal from the reader, or even from himself, such a su-premely conscious u,riter conceals, it seems to tlle, very little.
I wrote my blogs from last week partially on this topic. The message conveyed in this paragraph is trying to pick apart the art, the "words" of a particular piece from the artist. This is why I think that a "Shakespearean sonnet", whether ajar or concise as it relates to the stereotypical "iambic pentameter structure" is still a Shakespearean Sonnet all the same.
"It is the workings of the verbal construct that give evidence of the moral stance of the poet." This line reminds me most of our readings of Sonnet 130 in class. In order to not only read that sonnet properly (voice, pitch, rhythm, feet) , but to properly understand the context of that sonnet, one has to understand how Shakespeare uses words. His use of iambic pentameter isn't to the effect of a feeling or a sound, but a direct meaning. The syllables stressed in his stanzas are used to indicate emphasis on certain words, such as "Her" or "lips" or "my mistress" in conjunction. The stressing of these words often come out of sync.
The effect given off when he manipulates the stress of these words can create a trochee or even a spondee at times, which would mean that the line isn't in iambic pentameter; yet, the poem itself is in iambic pentameter, because, indicated in the reading, the "total contraptionness... of any given sonnet [is] the first necessary level of understanding."
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y/ The teacher and I thought we had given the stu S dents the skills to productively discuss a text, but as soon as we pulled away to let them lead the group on their own instances like the previous example became far too frequent. For example, in another group that I was videotaping, what started as a civil discussion about the book rapidly declined into chaos when one boy called a girl "retarded." In turn, the girl responded, "Shut up! You boy don't know even how to dress your self." This conversation never got back on track as com ments such as "Rahsean really stinks right now, but like I was saying..." permeated the rest of the group's discus sion. In another group, two students continued kick ing each other throughout the meeting, which caused both students to miss questions asked by other mem bers and impeded their ability to engage with the text, not to mention disrupted other members.
I think that if kids are fighting in these groups, then there is a bigger problem than just behavior. There may be issues such as students not understanding the material, or finding it boring causing them to get off track.
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I am a fine, prize–winning horse, but I carry a man who is utterly base, and this causes me the greatest pain
I thought this was interesting for two reasons. First, does this quote suggest that who a person surrounds himself or herself with defines him or her? While it may be harder to remain upstanding while having base friends, I do not think it determines whether that person is base or not. It depends more on how the person handles the base actions of their friends. If they turn a blind eye or, worse, support bad actions, then I would agree the friend is making them worse off. However, if you can help a friend move away from poor actions, I think it may make the person better. Overall, I just thought this was an interesting commentary on socialization. Secondly, this relates to symposium decorum, as we have discussed. Having base individuals at a dinner may impede upon the status of the event. Individuals with bad reputations or who will act out are a weight to the event. While everyone else in the room may be good and upright individuals, but they will be brought down by a morally questionable individual. It is important to be very careful about who you bring to the dinner.
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Yet there may be a sort of inadvertent benefit. Humanity may be more special than it seems. As Brownlee and Ward put it: "We are not the center of the universe, and we never will be.
This shows one of the points I brought up in my research. We used to think that God made us the center of everything and that we were the most important but in reality, we are very small compared to the universe.
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On 2017 Feb 10, David Attwell commented:
The answers to Dr Brette’s new points are as follows.
(1a) Ohmic vs Goldman dependence of current on voltage
For a cell as assumed in Attwell & Laughlin (2001) (i.e. 200 Megohm membrane measured with a 10mV hyperpolarizing step, VNa=+50mV, VK=-100mV, Vrp=-70mV, [Na]o=[K]i=140mM, T=37C), assuming a Goldman voltage dependence for the Na<sup>+</sup> and K<sup>+</sup> fluxes through ion channels leads to PNa/PK=0.0746 and a Na<sup>+</sup> influx at the resting potential of 130pA, corresponding to an ATP consumption of 2.7x10<sup>8</sup> molecules/sec. This is 21% less than the 3.42x10<sup>8</sup> molecules/sec we calculated using an ohmic dependence of the currents on voltage. This difference is negligible given the variation of measured input resistances and the range of other assumptions that we needed to make. Furthermore, there are no data establishing whether the voltage-dependence of Na+ influx is better described by an ohmic or a Goldman equation.
(In a later post Dr Brette claims that the error arising is 40%. We suspect that his value arises from forgetting the contribution of the Na/K pump current to setting the resting potential, which leads erroneously to PNa/PK=0.05, and a 41.3% lower value than the ohmic dependence predicts.)
(1b) Cl<sup>-</sup> permeability
Our point was that the Cl<sup>-</sup> permeability was negligible. Which equation was used to derive that fact is therefore irrelevant.
(2) Pumps
We still disagree with the notion that, for a membrane with just Na<sup>+</sup> and K<sup>+</sup> fluxes, the system is unstable if it only has a Na/K pump. The Na pump rate is adjusted to match activity via its dependence on [Na<sup>+</sup> ]i and by the insertion of more pumps when needed.
(3) Cost of Na<sup>+</sup> extrusion at the mean potential
Tonic synaptic activity may depolarize cells by a mean value of ~4-8mV (Paré et al., 1998, J Neurophysiol 79, 1450). This will affect the calculation of “resting” Na+ influx negligibly (e.g. by ~6mV/120mV = 5% for a 6mV depolarization with Vrp=-70mV and VNa=+50mV). As stated in our earlier comment, this depolarization does not affect the ATP used per Na<sup>+</sup> pumped by the Na/K pump. Finally the ATP used on extruding synaptic ion entry is considered separately in the calculations.
(4) What input resistance tells us
For cortical L2/3 pyramidal cells the majority of the membrane area is in the basal dendrites, which have an electrotonic length of ~0.24 space constants, while the apical dendrites have an electrotonic length of ~0.69 space constants (mean data at body temperature from Trevelyan & Jack, 2002, J Physiol 539, 623). Larkman et al. (1992, J Comp Neurol 323, 137) similarly concluded that most of the dendrites of L2/3 and L5 pyramidal cells were within 0.5 space constants of the soma.
Elementary cable theory shows that, for a cable (dendrite or local axon) with a sealed end, with current injection at one end, the ratio of the apparent conductance to the real conductance, and thus the ratio of our calculated ATP usage (on Na<sup>+</sup> pumping to maintain the cable’s resting potential) to the real ATP usage, is given by (1/L).(exp(2L) - 1)/(exp(2L) + 1) where L is the electrotonic length (cable length/space constant). For L=0.24, 0.5 and 0.69, respectively, this predicts errors in the calculated ATP use of 1.9%, 7.6% and 13.3%, which are all completely negligible in the context of the other assumptions that we had to make.
For the axon collaterals near the soma, there is less information on electrotonic length, but the few measurements of axon space constant that exist (Alle & Geiger, 2006, Science 311, 1290; Shu et al., 2006, Nature 441, 761) suggest that the axon collaterals near the soma will similarly be electrically compact and thus that their conductance will be largely reflected in measurements of input resistance at the soma. We excluded the part of the axon in the white matter from our analysis, but did include the terminal axon segments in the grey matter (where the white matter axon rises back into a different cortical area. Re-reading after 16 years the source (Braitenberg & Schüz, 1991, Anatomy of the Cortex, Chapter 17) of the dimensions of these axons, it is clear that those authors were uncertain about the contribution of the terminal axon segments to the total axon length, but assumed that they contributed a similar length to that found near the soma in order to account for the total axon length they observed in cortex. It is unlikely that these distant axon segments will contribute much to the conductance of the cell measured at the soma but, partly compensating for this, part of the axon in the white matter will. This, along with the electrical compactness of the dendrites and proximal axons discussed above, implies that our calculated ATP use on the resting potential is likely to be correct to within a factor of 1/f = 1.57 (where f=0.64 is the fraction of the cell area that is electrically compact [ignoring the minor voltage non-uniformity quantified above], i.e. the soma, dendrites and proximal axons, calculated from the capacitances in Attwell & Laughlin and assuming that the proximal axons provide half of the total axon capacitance in the grey matter).
In fact the situation is likely to be better than this, because this estimate is based on membrane area, but ATP use is proportional to membrane conductance. Estimated values of the conductance of axons (Alle & Geiger, 2006, Science 311, 1290) suggest that the specific membrane conductance per unit area in axons is significantly lower than that in the soma and dendrites (see the Supplementary Information section on Granule Cells in Howarth et al. (2010) JCBFM 30, 403), which reduces the ATP used on maintaining the resting potential of axons.
General reflections on what people expect from the Attwell & Laughlin paper
Our paper tried to introduce a new way of thinking about the brain, based on energetics. Given the large number of assumptions involved it would be a mistake to expect individual values of ATP consumption to be highly accurate. Remarkably, the total energy use that we predicted for the grey matter turned out to be pretty well exactly what is measured experimentally. Nevertheless, constant updating of the assumptions and values is, of course, essential. It is interesting that the value we derived for the ATP used per cell on the action potential (3.84x10<sup>8</sup> ATP) was initially revised downwards nearly 4-fold in the light of papers showing less temporal overlap of the voltage-gated Na<sup>+</sup> and K<sup>+</sup> currents than occurs in squid axon (Alle et al., 2009, Science 325, 1405), but has increased with more recent estimates back to be close to our original estimate (3.77-8.00x10<sup>8</sup> ATP, Hallermann et al., 2012, Nature Neuroscience 15, 1007).
The most important assumption that we made was that all cells were identical, which immediately implies that this can only be an approximate analysis. We were very happy that the total energy use that we predicted from measured ionic currents, cell anatomy and cell densities was so close to the correct value.
General reflections on post-publication peer comments
We believe that if someone has questions about a paper then the most productive way to get them answered is: (i) to think about the issues; if that fails (ii) to write to the authors and ask them about the questions, rather than posting some vague and erroneous comments that will forever be linked to the paper, regardless of their validity; and if that fails (iii) to write a paper or review which goes through peer review, pointing out the problems. Peer review is crucial for determining whether the points are valid or not - it potentially saves many readers the time needed to read possibly erroneous comments.
It takes a long time to reply to such comments, and we feel that Dr Brette could have done the calculations that we have provided in our two sets of responses. We will not be posting further responses therefore.
David Attwell & Simon Laughlin, 09-02-17
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On 2016 Jul 23, Lydia Maniatis commented:
This article is illustrative of the degradation of theory and practice in vision science. The article is not new (but compare with, e.g. Graham, 2011), but many of its assumptions and the style of argument - tolerance for layers upon layers of uncorroborated assumptions and inadequate, ad hoc models - are still very current and underpin a broad swath of contemporary (arguably pseudoscientific) activity. Below are quotes from the article and my comments.
The abstract: "Light adaptation has been studied using both aperiodic and periodic stimuli. Two well-documented phenomena are described: the background-onset effect (from an aperiodic-stimulus tradition) and high-temporal-frequency linearity (from the periodic-stimulus tradition). These phenomena have been explained within two different theoretical frameworks. Here we briefly review those frameworks. We then show that the models developed to predict the phenomenon from one tradition cannot predict the phenomenon from the other tradition, but that the models from the two traditions can be merged into a class of models that predicts both phenomena."
Comment: One wonders whether the merger was ultimately successful, and whether falsifying phenomena from yet other traditions could be merged with these two, to expand the ever-expanding ad hoc circle of tradition.
Note that the piecemeal "merger" philosophy expressed by Graham and Hood seems to preclude falsification. Falsifying phenomena from another "tradition" simply lead to the summing of individual ad hoc models into a compound ad hoc model, and so on. The complexity but not the information content of the models will thus increase. (This will also likely produce internal inconsistencies that not be noticed because they will not be looked for.) The question of whether these models correspond with the facts that they are supposedly trying to explain never really arises.
All this can be garnered from the abstract: If anything, the text is even worse.
"None of the parts of the merged models, however, is necessarily correct in detail. Many modifications or substitutes would clearly work just as well at this qualitative level. …Also, one could certainly expand the model to include more parts. …Similarly, the initial gain-controlling process might be composed of several processes having somewhat different properties"
Comment: The models are arbitrary, ad hoc, incomplete on their own terms, and there is no rational criterion for choosing among an infinite number of alternatives.
"No attempt was made to fine-tune either model to predict all the details in any one set of psychophysical data…much less in all the other psychophysical results that such a model might bear on…To attempt such a project in the future might be worthwhile...particularly if the experimental results were all collected on the same subjects..."
Comment: In other words, because the models are ad hoc they may only explain the results to which they were tailored. It may (or may not??) be worth checking to see whether this is the case. I.e. testing models for correspondence with the phenomena is optional. The effects in question are too fragile and too little understood to be tested across subjects with varying methods.
"The more vaguely-stated possibility suggested by this observation, however, is that any decision rule of the kind considered here may be in principle inadequate for the suprathreshold-discrimination case. It may be impossible to explain suprathreshold discriminations without more explicit modeling of higher-level of higher-level visual processes than is necessary to explain detection (where detection is a discrimination between a stimulus and a neutral stimulus.)... Thus a simple decision rule may be suitable in the detection case simply because all the higher-level processes are reduced to such simple action THAT THEY BECOME TRANSPARENT." [caps mine].
Comment: The idea that there are certain experimental conditions in which the conscious percept consists in the reading off of the activity of "low-level" neurons (as though there was a direct qualitative correspondence between neural firing and seeing, e.g., a blank screen!) is patently absurd and has been criticized in depth and from different angles by Teller (1984).
Pretending that we take it seriously, we could refute it by noting that the presumably simplest of all stimuli - a white surface free of any imperfections - produces the perception of a three-dimensional fog. Other experiments have also shown that organizational processes are engaged even at threshold conditions, and that, indeed, they influence thresholds.
The "transparency theory" is repeated by Graham (2011) in an article in Vision Research: "It is as if the near-threshold experiments made all higher levels of visual processing transparent, therefore allowing the properties of the low-level analyzers to be seen."
This casually proposed "transparency" theory of near-threshold stimulation is apparently the basis of the widespread belief in spatial frequency channels and the extraordinary elaboration of associated assumptions. Without the transparency theory, it is not clear that even cherry-picked evidence can support this popular field of research. (If you've ever wondered at the widespread use of "Gabor patches" in vision research, this is the root cause - they are considered elemental due to the transparency theory-supported low-level neuron spatial frequency sensitivity hypothesis. I suspect many of the people using then don't even know why).
Graham and Hood (1992) also go into a little finer detail about the putative basis of transparency: " In the suprathreshold discrimination case, the observer is trying to discriminate between two sets of neural responses…both of which sets contain many non-baseline responses. In the detection case…the observer is simply trying to detect some non-baseline responses in either set (since that is the set most likely to be the non-blank stimulus). Thus a simple decision rule may be suitable in the detection case simply because all the higher-level processes are reduced to such simple action that they become transparent."
Comment: The suggestion that investigators are managing to set their low-level visual neurons at baseline at the start of experiments also seems implausible. I certainly don't think this has been explicitly discussed from the point of view of method. "However, at this moment in time, we seem to be able to explain background onset with a subtractive process…Thus, we can just leave as a marker for the future – should troubles in fully explaining the data arise – the possibility that the background-onset effect in particular (and perhaps all the results) will not be explained in detail without including more about higher-level visual processing."
Comment: Translation: We'll accept our ad hoc hypo thesis for now, but it's probably wrong. But we'll worry about that later, if and when anyone makes trouble by bothering with actual tests. Because there's always a (zero) chance that it will be corroborated.
Finally, the article also provides a good example of misleading use of references: "Quantal noise exists in the visual stimulus, as is well known (see Pelli for a current discussion.)"
Comment: From Pelli, 1990: "It will be important to test the model…For gratings in dynamic white noise, this [model] prediction has been confirmed by Pelli (1981), disconfirmed by Kersten (1984) and reconfirmed by Thomas (1985). More work is needed." But we don't need to wait for evidence to firmly believe in "quantal noise."
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On 2015 Dec 28, Lydia Maniatis commented:
Part 1. I have criticized Purves and colleagues' various iterations of the “wholly empirical” account of visual perception in various comments on PubMed Commons and on PubPeer. Here, I want to present a more comprehensive and organized critique, focussing on a study that has served as a centerpiece of these accounts. I think it is important to clarify the fact that the story is profoundly inadequate at both the conceptual and the methodological levels, and fails to meet fundamental criteria of empirical science (logical consistency and testability). Such criticism (which is not welcome in the published literature) is important, because if “anything goes” in published research at even the most elite journals, then this literature cannot help to construct the conceptual infrastructure necessary for progress in the visual sciences.
Conceptual problems LACK OF THEORETICAL MOTIVATION The hypothesis that the authors claim to have tested is effectively conjured out of thin air, subsequent to an exposition that is inaccurate, inadequate, and incoherent.
The phenomenon to be explained is inadequately described. We are told, first, that the luminance of a “visual target” elicits a “brightness” percept that can vary according to “context.”
The term brightness, here, is being used to refer to the impression of white-gray-black that a surface may elicit (and which is currently referred to by researchers as its “lightness.”) However, surfaces do not necessarily, or even usually, elicit a unitary percept; they often produce the impression of double layers, e.g. a shadow overlying a solid surface. Both the shadow and the surface have a perceptual valence, a “brightness.” Indeed, it is under conditions where one “target” appears to lie within the confines of a double layer, and the other does not, that the most extreme apparent differences between equiluminant targets arise.
The logic is simple: If a surface appears to lie under a shadow, then it will appear lighter than an equiluminant target that appears to lie outside of the shadow, because a target that emits the same amount of light under a lower illumination as one under stronger illumination must have a higher light-reflecting tendency (and this is what the visual system labels using the white-gray-black code.). The phenomenon and logic of double layers is not even intimated at by these Yang and Purves (2004); rather, the impression created is that the relationship between “brightnesses” under different “contexts” is not in the least understood or even amenable to rational analysis. (In addition, the achromatic conditions being considered are rare or even non-existent in natural, daytime conditions; but the more complex phenomenon of chromatic contrast is not mentioned.)
After this casual attempt to convince readers that vision science is completely in the dark on the subject of “brightness,” the authors assert that “A growing body of evidence has shown that the visual system uses the statistics of stimulus features in natural environments to generate visual percepts of the physical world.” No empirical studies are cited or described to clarify or support this rather opaque assertion. The only citation is of a book containing, not evidence, but “models” of brain function. The authors go on to state that “if so, the visual system must incorporate these statistics as a central feature of processing relevant to brightness and other visual qualia.” (It should be noted that the terms “statistics” and “features” here contain no concrete information. The authors could be counting the stones on Brighton beach.)
Even if we gave the authors the latitude to define “statistics” and “features” any way they wish, the following sentence would still come out of the blue: “Accordingly, we propose that the perceived brightness elicited by the luminance of a target in any given context is based on the value of the target luminance in the probability distribution function of the possible values that co-occur with that contextual luminance experienced during evolution. In particular, whenever the target luminance in a given context corresponds to a higher value in the probability distribution function of the possible luminance values in that context, the brightness of the target will be greater than the brightness elicited by the same luminance in contexts in which that luminance has a lower value in the probability distribution function.”
This frequency-percept correlation, in combination with the claim that it has come about on the basis of evolution by natural selection, is the working hypothesis. It is a pure guess; it does not follow naturally from anything that has come before, nor, for that matter, from the principles of natural selection (see below). It is, frankly, bizarre. If it could be corroborated, it would be a result in need of an explanation. As it is, it has not been corroborated, or even tested, nor is it amenable to testing (see below).
THE HYPOTHESIS The hypothesis offered is said to “explain” a narrow set of lightness demonstrations. Each consists of two displays, both containing a surface of luminance x; despite being equiluminant, these surfaces differ in their appearance, one appearing lighter than the other.
The claim is as follows: The visual system has evolved to represent as lighter those surfaces that appear more frequently in one “context” than in another. Thus, in each display, the surface that appears lighter must have been encountered more often in that particular “context” during the course of evolution. It is because seeing the higher-frequency target/context combination as lighter was “optimal” this situation arose. More specifically, it is because the response “lighter” to a target in one “context” and “darker” to a target in another context, and so on for contexts in-between, has had, over evolutionary time, positive adaptive effects, that these percepts have become instantiated in the visual process.
DO ORGANISMS TRACK ABSOLUTE AND RELATIVE LIGHT INTENSITY OVER MOMENTS, HOURS, DAYS, EONS, AT ALL POINTS IN THE RETINAL IMAGE, AND WHEN DID THEY STOP DOING THIS? The hypothesis would appear to presuppose that organisms can discriminate between, and keep track of, the absolute luminances of various “targets” in various “contexts,” as they have been encountered with every glance, of every individual (or at least the ancestors of every individual), at every point in the visual image, every moment, hour, day, across the evolutionary trajectory of the species. There is no suggestion as to how these absolute luminances might be tracked, even “in effect.” Not only is it difficult to imagine what mechanism (other than a miracle) might allow such (species-wide) data collection (or its equivalent) to arise, it runs contrary to the physiology of the visual system, in which inhibitory mechanisms ensure that relative, not absolute, luminance information, is coded even at the lowest levels of the nervous system. Furthermore, given that lightness perception does not change across an individual's lifetime, nor depend on their particular visual experience, it would seem that this process of statistical accumulation must have stopped at some point during our evolution. So we have to ask, when do the authors suppose this (impossible) process to have stopped, why did it stop, and what were the relevant environments at that time and previously? (The logical assumption that the authors suppose the process has, in fact, stopped is reinforced when they refer to “instantiated” rather than developing “statistical structures.”)
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On 2014 Jan 04, Tom Kindlon commented:
The dropping of actometers as an outcome measure and other points relating to the outcome measures being used
(I'm posting this e-letter/comment from 2008 here for the same reason as the first e-letter below)
In their reply to my comments, Peter White and colleagues say they are using [i]"several objective outcome measures"[/i] [1]. If they think these tests are useful as objective outcome measures, why is at least one of them not being used as a primary outcome measure rather than the current situation where there are only two subjective outcome measures being used.
I have already made some points on the outcome measures but another one is that the bimodal Chalder Fatigue Scale hardly seems a very good outcome measure for a "CFS/ME" trial where there is likely going to be so many maximum or near maximum scoring initially[2]
Also, there are so many (14) secondary outcome measures in this study, along with so many (18) predictor variables, that it seems unlikely all the different methods of looking at the secondary outcome measures can be explored in the final published paper, given authors are encouraged not to make papers too long (especially journals that have paper editions). The protocol itself is 20 pages long when all the different aspects of it are listed! At least some of the information will need to be re-iterated in the final paper.
It is of course important to take the burden on participants into account when deciding what outcome measures to use. However I find the following point very strange: "Although we originally planned to use actigraphy as an outcome measure, as well as a baseline measure, we decided that a test that required participants to wear an actometer around their ankle for a week was too great a burden at the end of the trial." Firstly they clearly don't find it that great a burden that they drop it altogether as it is being used on patients before the start. If they feel it was that big of a burden, it should probably have been dropped altogether.
Of course, other studies in the area have used measuring over a similar or longer period. For example, Bazelmans [3] used an actometer over 14 days, Black [4] used actigraphy over 14 days, Sisto[5] used actigraphy over 7 days, Vercoulen[6] used an actometer over 12 days and Van der Werf [7] used an actometer for 12 days.
Also if one wants to reduce the burden on patients, why not take out one or both of the exercise tests instead. As the clinicians in the study would know, post-exertional symptoms are part of the condition.
For example, Nijs[8] performed a gentle walking exercise on patients where they walked on average 558m(+/-340) (range: 120-1620) at a speed of 0.9m/s (+/-0.2) (range: 0.6-1.1). This resulted in a statistically significant (p<0.05) worsening of scores in the following areas when comparing pre-exercise, post-exercise and 24 hour post-exercise scores using ANOVA: VAS fatigue, VAS musculoskeletal pain, VAS sore throat, SF-36 bodily pain and SF-36 general health percention. 14 out of 24 subjects experienced a clinically meaningful change (worsening) in bodily pain (i.e. a minimum change of the SF-36 bodily pain subscale score of at least 10).
Those results are similar to another study[9] which involved the acute effects of 10 discontinuous 3-minute exercise bouts on a treadmill in 10 CFS patients. In between exercise bouts, there was a 3-minute recovery period between exercise bouts. The participants walked at a comfortable walking pace self-selected by the subjects. On average, the subjects walked at a speed of 0.71+/-0.20 m/s. Some patients reported experiencing headaches, leg pain, fatigue or sore throats.
In another study, Lapp [10] (not to be confused with Clapp[9]) reported on the effects of 31 patients to his practice who were asked to monitor their symptoms three weeks before to 12 days after a maximal exercise test. 74% of the patients experienced worsening fatigue and 26% stayed the same. None improved. The average relapse lasted 8.82 days although 22% were still in relapse when the study ended at 12 days. There were similar changes with exercise in lymph pain, depression, abdominal pain, sleep quality, joint and muscle pain and sore throat.
These are just a small selection of the studies which show patients experience an exacerbation of their symptoms following exercise testing. So these are the sorts of symptoms the patients may expect following the exercise. This reminds me that there seems to be a lot of concentration on measuring fatigue in this study - there are many other symptoms that are part of "CFS/ME".If they had used actometers instead of, say, doing one of the exercise tests, the response to the exercise could have been followed to see how long and how severe an effect the exercise had on the patient. Or they could have dropped both the exercise tests altogether.
As well as "subjective" findings following exercise testing, there have also been objective findings. Arnold et al[11] found excessive intracellular acidoss of skeletal muscles with exercise. Jammes[12] found an increase of damaging oxidative stress following exercise testing. So patients could not just endure temporary sysptom but possibly also longer-term harm from exercise testing. There are numerous other exercise abnormalities.As the clinicians involved in the study probably hear from patients, one of the frustrating things about ME or CFS is that people don't realise the payback that they can have from doing things. This would have been an opportunity to investigate this as part of the study. But now the effort patients will put in and the payback they will feel in some ways is being wasted as the effects won't be measured.
Anyway, to repeat again, given the authors familiarity with the literature, I find it strange that they would decide using an actometer would be worse than putting patients through two exercise tests.
I also find it surprising that in a study part-funded by the Department of Work and Pensions (DWP) that the objective outcome measures (not involving questionnaires) are all once-off exercise tests. It has been established that patients need to be able to do things on several days during a week before they can be passed fit for work. I have mentioned using actometers following exercise tests after an exercise test above; of course, actometers wouldn't have to be used at that time but also during a "normal week".
Proponents of pacing methods including APT would say that there is a "ceiling of activity" that patients can't go above without experiencing a worsening of symptoms. Black[13] has found evidence of this. Proponents of CBT or GET for "CFS/ME" would suggest that patients can gradually just increase how much activity they can do. Actometers would also have tested the hypothesis. As it stands, the study will not give us information on this as just because patients answer questionnaires saying they're improved (which could simply be because they think they're better) or improve their exercise results (which might simply be because they're willing to push themselves more) doesn't prove that they don't have an activity ceiling above which they experience disabling symptoms (esp. when, as in this study, there is no follow-up period following the exercise testing). This is the real "heart" of the issue but given the current design, the question won't be answered.
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On 2015 Dec 06, Mark Bolland commented:
This comment provides background information to an earlier comment.
We were interested in why different meta-analyses of vitamin D supplements came to different conclusions, and noticed that different meta-analyses used different data from this trial. We identified several errors/inconsistencies in the text and emailed the lead author requesting clarification about the data in March 2014. He responded that the data in the Tables were correct. We replied that there were inconsistencies within the Tables as well and asked for clarification, but he did not respond.
Therefore in April 2014, we contacted the editor of Osteoporosis International advising the editor of the inconsistencies and requested that they be corrected. We felt this is particularly important as it is a highly cited, influential trial reporting benefits of vitamin D supplements on falls, and the inconsistencies occur in the treatment group numbers and the primary and secondary outcomes, so have a major bearing of the interpretation of the trial results. Our primary concern was/is to use the correct data for the trial in meta-analyses. In May 2014, the editor passed on an extract of the lead author’s response and indicated that an erratum would be published. However, we felt the lead author’s response was inadequate because it left a number of uncorrected inconsistencies/errors in the text. We pointed this out to the editor. We are not sure what action the editor took, but no erratum was published. We followed up with 2 further emails to the editor over the next year, and in April 2015, the editor advised that it seemed unlikely that an erratum would be forthcoming.
Therefore, we requested the permission to summarize the issues in a very brief letter. The editor agreed and a short letter summarizing the six errors/inconsistencies in the article was published (Osteoporos Int 2015;26:2713 Bolland MJ, 2015) with a response from the author (Osteoporos Int. 2015;26:2715-6 Pfeifer M, 2015). Unfortunately, in his response the author chose to correct only 2 of the errors identified and introduced a further inconsistency.
In a further letter to the editor, we therefore highlighted the remaining errors/inconsistencies and the consequence of using different possible data combinations from this trial for meta-analyses. The editor indicated that the issues we raised were important but probably irresolvable and offered to publish the letter in Archives of Osteoporosis. We indicated that our preference was that the data were corrected in the original publication rather than our letter being published. We think it quite straightforward to make the simple necessary corrections to two tables and a couple of sentences of text. We feel it is essential that the corrections occur as the errors are in the most important data from the trial: the treatment group numbers and the primary outcome data for falls. The editor considered the issue further and then published our letter (Arch Osteoporos. 2015;10:43 Bolland MJ, 2015) along with a response from the author (Arch Osteoporos. 2015;10:42 Pfeifer M, 2015).
In this second response, the author has still not corrected the identified errors, so, because of the inconsistencies/errors in the data, it is not possible to be sure how many women were in each randomized treatment group, how many women had a fall during the trial, how many total falls occurred in each treatment group, or what is the breakdown of participants by numbers of falls (no falls, 1 fall, 2 falls, etc).
Therefore, we think that the study should be excluded from meta-analyses and systematic reviews and its results viewed with caution until consistent data are provided by the authors with some explanation as to how the errors/inconsistencies occurred.
Mark Bolland, Andrew Grey. University of Auckland
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On 2014 Jan 12, Brett Snodgrass commented:
Dear Authors,
Thank you very much for the excellent publication and acknowledging that the connections between the coronary arteries and left ventricle were not probably not veins.
These connections may represent the vessels of Wearn, which appear unusually prominent.
An applicable ICD9 code might be 746.85, coronary artery anomaly, as it may meet the clinical criteria for the definition of fistulae.
Referring to these arterial connections as Thebesian veins has caused me much confusion when I was trying to understand the simple relationship of pulmonary atresia with intact ventricular septum and the coronary arteriopathy seen in PAIVS. With the growth of social media, and electronic data storage, I think that we may now be able to address the diffuse distribution of ambiguous or misleading nomenclature that fills as least half of related publications.
Dr. Paul Lurie's plea for collaboration in this regard has motivated me to take several steps in an effort to try to help produce accurate, simple, precise anatomic nomenclature and include:
I collaborated with Elsevier to help get the article by Wearn et al. changed to open-access. http://bit.ly/JTWearn
I obtained the original article (through ArtRieve http://www.artrieve.com/) written by Thebesius and uploaded the first digital copy. http://bit.ly/Thebesius
I published or wrote in the American Journal of Cardiology, Cardiovascular Pathology, Twitter, Facebook, Google Plus, and directly E-mailed several authors that were publishing related content.
I have posted numerous PubMed Commons comments. I regret that they may not always be helpful to every user, but I echo Dr. Lurie’s plea for collaboration in this regard. The PubMed Commons commentary is a welcome means with significant potential to vastly improve the peer review process.
My aim is that researchers in the future will probably not need to read more than 30 articles before they realize that myocardial sinusoids indeed exist, they were defined by Wearn, and that Thebesian veins are not arteries.
Please see
My opinion is that accurate anatomic terminology is a basic principle underlying good medical science, and I ask others to consider whether the aforementioned definitions are appropriate. If this comment is not helpful, please let me know how it might be improved.
Comments and suggestions are welcome.
Thank you very much.
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On 2014 May 05, Madhusudana Girija Sanal commented:
Creativity in biology-reply to Bruce Alberts
Bruce Alberts, describes biology as 'not at all an easy science' (1). This entirely depends on the definitions of boundaries! Biology is more factual and visual (and hence ‘easy’ for majority) than physics and mathematics. However, biology attains the same degree of difficulty at its interface with these subjects were mathematics or physics is applied to answer biological questions.This relative ease may be one of the reasons we find more students graduating in biology than other basic sciences (2). Creativity in the generation of new ideas and concepts is the essence of science. The current 'reward-recognition' system which just counts the papers is not recognizing this fact. The current trend is to evaluate scientists on the basis of the number of publications and their impact factors rather than their impact on the growth of science and the betterment of the society. This has resulted in a ‘publish or perish’ situation leading to an increase in junk and fraudulent publications (2). The cracking of the central dogma in biology or the invention of PCR brought new concepts in biology. Personalized medicine, designer molecules and proteins and regenerative medicine have huge potential. However,currently the society is wasting its resources in premature translational research and personalized medicine which are growth arrested in infancy, awaiting major developments in technology to overcome the bottlenecks (3). Any significant leap in biology needs a major leap in chemistry, physics and mathematics. These subjects provide not only technology and tools but also concepts for the growth of biology. So funding and research in other fields need be encouraged for the development of biology (2).
Life Sciences-where ‘workers’ take a lead over thinkers!
The number of publications in biology is proportional to the amount of ‘work done’ rather than “adventure of ideas”. This is causing many problems. For example this results in the dissolution of the boundaries between a scientist, a technician and a robot (2). The number of papers and the journals in which they are published often becomes a matter of chance, available workforce, availability of funds and collaborations which in turn depends on politics, influence and umpteen other factors decreasing the overall importance of intellect on scientific publication. It is difficult to assess individual contributions of the authors-who contributed more for the concept and who did most of the (technician) work-from a research article. Needless to say that who contributed towards the development of the concept should be given more credit. But this is rarely practiced (2).
The future of Biology
We are still taking the same cereals, pulses, milk and meat, which existed thousands of years before! We have yet not created any new plant or animal! Currently in biology, we move in a top to bottom fashion i.e.; explore the existing biological systems and reveal the science behind them and copy it, re-engineer it, according to our need. For example, find out a gene, find its importance, function, the protein coded, structure, interactions etc But I feel biology mature enough to think moving the other way i.e.; design a gene according to our need-plan its structure function, interactions etc according to our need design it. If I extend this view we should be able to engineer and produce totally new proteins or organisms rather than building or modifying from an existing (natural) platform (2).
Other major advancements will be in creating brain-computer interfaces and computer assisted thinking, electronic immortalization of personalities (individuals), planned generation of citizens of varying functions and capabilities for the better service of the society etc. For all this to happen the limiting step is the development of basic sciences which could then be easily translated to appropriate technologies.
1) Alberts B.Creativity at the interface. Science. 2012 Apr 13;336(6078):131. 2) Sanal MG Where are we going in science? Publish and perish! Current Science 2006 3) Maher B. Nature.Tissue engineering: How to build a heart. 2013 Jul 4;499(7456):20-2
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On 2015 Apr 02, Marcus Munafò commented:
Flegal and colleagues suggest that being overweight may decrease risk of all-cause mortality, and being slightly obese confers no increased risk compared to being of normal weight [1]. We think these conclusions are misleading and may give a detrimental public health message, particularly given the publicity they attracted.
Despite the authors’ suggestion that there is “little support for the suggestion that smoking and pre-existing illness are important causes of bias”, these factors are not consistently controlled for within the contributing studies [1]. It has been demonstrated in two large prospective studies that the increased risk of death from being overweight or obese can be masked when smoking is not adequately controlled for, and when sufficient initial years of follow up are not excluded [2]. Smoking is associated with both lower body mass index (BMI) and increased risk of death, while underlying illness can lower BMI prior to death. Furthermore, it is widely appreciated that conventional statistical approaches to “control” for such factors are inadequate. Support for a positive causal effect of BMI on mortality comes from studies less subject to the biases associated with BMI measured in later life because they used BMI in adolescence or offspring BMI as the exposure [3, 4]. These measures are suitable proxies since they are strongly associated with an individual’s BMI in middle age but are not substantially affected by reverse causality and are less confounded by smoking. Higher BMI in adolescence was associated with greater risk of all-cause mortality in middle age in a study of over 200,000 individuals [3]. Stronger inferred associations were observed with offspring BMI and all-cause and cardiovascular mortality than with own BMI, suggesting that positive associations of BMI and mortality may in fact be underestimated in conventional observational studies [4]. In addition, this study demonstrated that the commonly observed inverse association between BMI and death from respiratory and other diseases may also be due to such biases.
Given the importance of the public health messages regarding “healthy” weight, we feel that further research is needed in this area using innovative research methods to overcome potential biases; further conventional observational studies will simply recapitulate the biases inherent in all such investigations. One such approach would be Mendelian randomisation, using obesity-related genetic variants, such as those in FTO. Mendelian randomisation methods, when applied correctly, are free from confounding by environmental factors and are not affected by reverse causality [5].
Marcus Munafò, Amy Taylor and George Davey Smith
- Flegal, K.M., et al., Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA, 2013. 309(1): p. 71-82.
- Lawlor, D.A., et al., Reverse causality and confounding and the associations of overweight and obesity with mortality. Obesity (Silver Spring), 2006. 14(12): p. 2294-304.
- Bjorge, T., et al., Body mass index in adolescence in relation to cause-specific mortality: a follow-up of 230,000 Norwegian adolescents. Am J Epidemiol, 2008. 168(1): p. 30-7.
- Davey Smith, G., et al., The association between BMI and mortality using offspring BMI as an indicator of own BMI: large intergenerational mortality study. BMJ, 2009. 339: p. b5043.
- Davey Smith, G. and S. Ebrahim, 'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol, 2003. 32(1): p. 1-22.
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On 2014 May 06, Madhusudana Girija Sanal commented:
Dr. Norman is picturing the great progress in education as a result of the information distribution revolution as if it is an ‘unavoidable evil’! Probably, many of his generation expresses high inertia, still consider, 'physical' universities, libraries, books, lecture halls etc. very much essential! I understand their nostalgia! You know what this means for humanity? Rich countries such as USA hold only a small fraction of the world’s population. Through virtual universities more and more people across the world, irrespective of rich and poor, would be able to attend the best schools and courses. They would be able to take the same exams and get ranked along with the most privileged, rich or intelligent. This would be great! This is 'new' justice! (Although I believe “Justice is ‘man made’ or artificial”). All we want is better tools to evaluate human intellectual qualities, online. I do not think face to face lectures will be better than online recorded, interactive lectures, may be multidimensional (3D-4D-5D) lectures by several professors of the learner’s choice. Lectures will be ranked and paid by based on their quality by student communities and not by bureaucrats or by administrators and politicians. This system is great especially when I consider the advantages! On demand, personalized lectures would be "ready-made" for commonly observed (student) personality traits -say there are 100 personality subtypes and intellectual levels! Custom lectures are available for them all because there are much more people to teach online-lectures need not be real time. You can learn from a "personality" who matches your rare personality, perhaps, one who lived 10 years back. His lectures had to wait for ten years for a student like you! Is not this a very exciting possibility? However, I do agree that face to face lectures can be more individualized and beneficial (for the rich, because they only have money to ‘buy’ good teachers!) Nevertheless, I do not think there is a huge benefit for extreme personalization except for exceptional children who are extremely out-of-the-box in a positive or negative way. It may be, however, noted that overall poor but brilliant students have a better opportunity to come out and stand before the world. This global free learning system will benefit specially those brilliant minds in less privileged countries. Do Dr. Norman has any evidence to support his statements in the editorial? I do not know what Dr. Norman will write if tomorrow we find a new technology which allows direct transmission of knowledge to brains! Then what will happen? Think! Everyone will have equal opportunity to accumulate the same amount of information if he or she wants. Now who will win this game? Those who have money? Probably not! Those fractions of the society who are blessed with right genome, epigenome and the best neural connections!
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On 2014 Aug 11, Dr. Priyanka. M Jadhav commented:
Ayurveda: science beyond scepticism and snake oil
Priyanka M. Jadhav, Research Scientist
Maharashtra University of Health Sciences
Comment on: Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial
Sir, This is the age when the concept of remote surgery does not surprise us, but we are not prepared to accept a concept that has existed and survived for centuries—the science of Ayurveda. I read with great interest the study published by Chopra et al. and am excited that the New Millennium Indian Technology Leadership Initiative (NIMTLI) project set up with an interdisciplinary approach is evaluating traditional and Ayurvedic drugs in clinical trials for treatment of osteoarthritis[1]. It is interesting to see how modern medicine approach is being used to study the effect of an Ayurvedic medicine assessed by a series of experiments [2–4]. The acceptance of Ayurveda or any other traditional system of medicine in western medicine is low; however, what causes frustration are the allegations and misinformation being promoted.
Recently, a a letter was published in which the author termed Ayurveda as quackery.[5] Patients and the next generation who aspire to find a cure and career in this age-old science find such information as very misleading and confusing. On the other hand, many other journals are documenting the reports on the study of these drugs.
The National Center for Complementary and Alternative Medicine clearly states the lack of randomized controlled clinical trial for complementary and alternative medicines and a need to build evidence-based datab to assess the plausibility of claims[6].
As an Ayurvedic practitioner, I welcome such suggestions and efforts, which are more than mere dismissal of age-old science. Although the current research and published papers concentrate on the extracts of plants, the point of holistic treatment is lost. As many scientists use extracts, the pressure of using purified extracts in studies is very high. Any researcher who proposes to work on a whole medicinal plant not only faces technical difficulties but also pressure from the scientific community, which again steers them to use purified extracts. Negative results of many experiments are not even published.
NMITLI arthritis project is one such attempt to translate the language of traditional medicine in a way that the western world can understand. In doing so, the scientists involved are those who are experts in their field and have done their best to generate data from in vitro and human studies. Moreover, one can also argue that Ayurveda treats a patient not only by medicine but also by other methods such as application of oil, hot fermentation, purgation, etc., which varies for each patient depending on their prakruti or constitution.[7] If one aims to study these medicines, a novel and innovative approach or a fresh perspective is needed when designing a suitable trial. [8]
More such studies as the one done by Chopra et al. should be done. Such studies will focus on chronic and infectious diseases, which are of grave concern not only for the developing or resource-poor countries but also for the developed world too. These medicines may form a good alternative, if not a substitute, for modern medicine that has mild to severe adverse effects particularly for chronic diseases. In a way, this study may be a base to prove to the funding agencies and other organizations that natural products can be just as effective as modern ones.
Some very important issues to be addressed are whether we are prepared to accept a concept riddled with prejudice or embrace one used by billions for their good for centuries.
References
1 Chopra A, Saluja M, Tillu G et al. Ayurvedic medicine offers a good alternative to glucosamine and celecoxib in the treatment of symptomatic knee osteoarthritis: a randomized, double-blind, controlled equivalence drug trial. Rheumatology 2013. doi: 10.1093/rheumatology/kes414. First published online: January 30, 2013.
2 Chopra A, Saluja M, Tillu G et al. Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: a Government of India NMITLI arthritis project. J Ayurveda Integr Med 2012;3:38-44.
3 Chopra A, Saluja M, Tillu G et al. A randomized controlled exploratory evaluation of standardized ayurvedic formulations in symptomatic osteoarthritis knees: a government of India NMITLI project. eCAM 2011;2011:724291.
4 Sumantran VN, Kulkarni A, Chandwaskar R et al. Chondroprotective potential of fruit extracts of Phyllanthus emblica in osteoarthritis. Evidence-based complementary and alternative medicine : eCAM 2008;5:329-35.
5 O'Cathail S, Stebbing J. Ayurveda: alternative or complementary? Lancet Oncol 2012;13:865.
6 Briggs JP. NIH. Turning discovery into health? Available from: http://nccam.nih.gov/about/offices/od/2011-06.htm (17 April 2013, date last accessed).
7 Dieppe P, Marsden D. Managing arthritis: the need to think about whole systems. Rheumatology 2013.doi: 10.1093/rheumatology/ket127 First published online: March 7, 2013.
8 Patwardhan B. Ayurveda GCP guidelines: need for freedom from RCT ascendancy in favor of whole system approach. J Ayurveda Integr Med 2011;2:1-4.
Conflict of Interest: None declared
Published July 9, 2013 http://rheumatology.oxfordjournals.org/content/52/8/1408.long/reply#rheumatology_el_105
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On 2014 Mar 21, Jacob Puliyel commented:
Williams and colleagues have described assessment of AEFI employing the algorithm described by Halsey < PMID: 22507656>.
I have posted two very detailed comments to an article by Tozzi Tozzi AE, 2013 which discusses the same subject of the revised WHO Classification of AEFI. I will not repeat the points I have made there but it may be viewed here.
As this is a matter of patient safety I think it is important that the experts who understand the new scheme must explain why the revision was needed and that it will not miss opportunities of picking up new signals. The question is whether the new scheme would have picked up and flagged the signal of adverse-effects like the RotaShield-reactions, had the scheme been in use in 1999. The purpose of this posting is to invite the learned authors of this article on causality assessment to respond to the issues raised in the postings to the Tozzi article and I propose to flesh out those concerns a little further in the context of the article in Pediatrics by Williams and colleagues.
1) Williams and colleagues Williams SE, 2013 suggest that the first step in the general approach to evaluating serious AEFI is to establish a clear diagnosis using Brighton Collaboration case definitions.
The second step is to consider known biological mechanisms.
Neither of these would have been evident when the intussusceptions signal was picked up by the old scheme (and the vaccine was withdrawn expeditiously preventing unnecessary distress to thousands of babies). Even today although a case definition has been developed for ‘intussusceptions’, the biological mechanism is not clearly defined and so the second step described by Williams et al cannot be completed.
It was reported recently that Pentavalent vaccine (DPT co-administered with measles vaccine (MV) and yellow fever (YF) vaccine) is associated with increased mortality compared to MV + YF alone Fisker AB, 2014. It is pertinent to mention that the biological mechanisms involved are not understood.
Neither is the biological mechanism for increased female mortality in recipients of the high-titer Edmonston-Zagreb vaccine known, although this was first noticed 2 decades ago. < PMID: 8237989>, Aaby P, 1993.
2) It will be instructive to look at how the new algorithm has failed to flag up the deaths following Pentavalent vaccine used in Asia (DPT + Hib + Hepatitis B) and as a result, numerous children continue to be exposed to the risks of this vaccine.
The glossary of the User Manual for the [Revised WHO classification]( who.int/vaccinesafety/publications/aevimanual.pdf) suggests ways and means to rule out a causal association. It defines causal association as a cause-and-effect relationship between the causative factor and a disease with no other factor intervening in the process.
There have been many deaths following use of this Pentavalent vaccine in Sri Lanka. The committee WHO vaccine safety examined 19 deaths in Sri Lanka, 14 of them between 2010 and 2012. In six of the 19, a congenital heart disease was reported.
Does preexisting congenital heart disease rule out a causal association between the vaccine and the deaths? Under this definition the 6 deaths in children with heart disease were not causally related to the vaccination.
The older Advisory Committee on Causality Assessment Collet JP, 2000 looked at the problem more logically and holistically. For example it noted that elderly persons with concomitant or preceding chronic cardiac failure can develop cardiac decompensation after influenza vaccination due to a vaccine-caused elevation in temperature or from stress from a local reaction at the site of vaccinating. The vaccine is considered to have contributed to cardiac failure in this specific situation. It is obvious that with the older method of assessment of AEFI, caution would have been exercised when administering influenza vaccine to persons with preceding chronic cardiac failure, to avoid decompensation.
The deaths in children with heart disease following administration of Pentavalent vaccine could well be due to decompensation. The Pentavalent vaccine must be used with caution in the presence of an underlying heart condition albeit asymptomatic. However detection of asymptomatic heart disease prior to vaccination in developing countries is impractical where the vaccine is administered by health workers who are barely literate. Is it prudent to use the vaccine under these circumstances given the findings of the Sri Lanka investigation? The new system disregards this real danger.
3) Step 2 Checklist 4 of the revised [WHO classification for causality assessment]( who.int/vaccinesafety/publications/aevimanual.pdf) asks to check if the event can occur independently of vaccination (background rate). Thus it seems that until the deaths from vaccine AEFI are frequent enough as to increase the age specific mortality-rate in a statistically significant manner, they are to be ignored.
The question of what background rate to use is not addressed specifically and this can further confound objective assessment of the AEFI. The Pentavalent vaccine in Asia is administered after 6 weeks of age. Would the local post-neonatal infant mortality rate (PN IMR) in the community before introduction of the vaccine be the comparator?
Most of this post-neonatal IMR is made of babies who are very sick with pneumonia, diarrhea, sepsis, meningitis etc. The fact that the AEFI babies were brought by the mother for routine immunization suggests that the child was not sick and the mother did not consider the child was likely to die in the next day or two. The comparator must really be the SIDS rate in the locality for babies of a comparable age.
Deaths in Bhutan were investigated and local newspapers reported on the various official explanations. It was argued that the deaths could have been due to encephalitis although there was little evidence for it. Officials explained that the encephalitis death rate in the years after the vaccine was introduced (even after adding AEFI deaths) had not increase significantly. This was sufficient grounds to accept the ‘coincidental encephalitis’ theory. One cheeky health official however pointed out that there were no cases of meningo-encephalitis reported among children below one year, in the eight months when Pentavalent vaccine was suspended in Bhutan.
4) Another factor related to the deaths following Pentavalent vaccine is that the vast majority have occurred after the first dose and fewer after the second dose. A random event or coincidental SIDS cannot explain these deaths. However the new algorithm does not take this important factor into consideration.
For all these reasons it would appear that the new algorithm is not a comprehensive means to assess serious adverse events. Its use will delay withdrawal of vaccines that result in serious AEFI and in the end it will erode confidence in the entire immunization programme and those who administer it.
Can I suggest that we need to go back use older scheme namely Brighton Classification of AEFI till we find a better method to assess AEFI.
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On 2014 May 22, L. Norton commented:
Nice work. Background is certainly an issue in ChIP-Seq studies and I think one way to deal with this is to examine gene expression of the proposed targets following knock-down of the transcription factor. Although this is not a perfect solution, after doing these experiments it becomes apparent that very few ChIP-Seq binding events are 'functionally significant' in a way that we expect (i.e. effect transcription). As a side note, I wonder if you or anyone else has examined the impact of sonication vs. MNase digestion on this phenomenon?
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On 2014 Jan 24, Tom Kindlon commented:
The validity of using subjective outcome measures as primary outcomes is questionable in such a trial
Crawley and colleagues suggest dropping school attendance as a primary outcome from the full study, and replacing it with self-report outcomes "such as the SF-36 or the Chalder Fatigue Scale" and using "school attendance as a secondary outcome"(1). And indeed, this is what they have done with the full study which has two primary outcome measures: "Chalder Fatigue Scale at 6 months" and "SF 36 physical function short form at 6 months"(2). I question the wisdom of using self-report measures as primary outcomes for such a trial.
The authors do not give much information about the details of the Lightning Process (they do mention it is "developed from osteopathy, life coaching and Neuro-linguistic programming (NLP))" but here are some descriptions from other sources (individuals who have undertaken a course) (note these are not descriptions from participants from the trial itself):
(a) "It felt very naughty but I whispered to one of the woman (sic) sitting next to me 'how are you, is this working for you?'. She was reluctant to answer, to say anything but that she was doing well would be to go against the process because that is a negative thought. It was pointless asking really. Still I wanted it to work, but I was starting to worry about the fact that I was not only not feeling any better the effort of doing the course, not getting my normal rest was making me feel worse. But these were negative thoughts. I started to ruthlessly suppress them like I had been shown." (3)
(b) “They tell you that you're not allowed to say that you're ill anymore or that you have any symptoms. They force you to ignore the symptoms because they say that the symptoms don't really exist. They force you to do activities even though it's making you really ill, but you're not allowed to say so.” (4)
Another, more thorough, description can be found on the Skeptic's Dictionary website(5).
I have seen many similar descriptions to these in discussions in many private fora. Here's one example: "So the first step in the process is to recognise when you’re in THE PIT. Maybe sometimes or all the time. It’s important to recognise what you say to yourself as you go into the pit. For example “I’m feeling really ill this morning”, “if I do this, then I’ll get exhausted”, “last time I did this I got really ill for days”, “I can never eat this” etc. This takes some practise but we were assured that you always say something in your head as you go into the pit. As soon as you spot one of your “pit” phrases you want to STOP yourself right away. So imagine you’re on the mat and you start to say “I feel really ill today”. Before you get to the end of this phrase you will interrupt with a very firm, loud “STOP” (yes, talk out loud to yourself!) and jump into the STOP position as described above. So you jump outside the mat, to your left. Now you’re here you have interrupted your bad thought patterns."
In essence when one is doing the lightning process, both during the three days training and after, you are to declare yourself well. You are not to say (or think) you have symptoms and you are not to say (or think) you have limitations. In other words, patients are 'trained' to dismiss and deny their symptoms and illness. Patients are instructed not to “do” ME or CFS anymore. In such a scenario, subjective reports from the patient are no longer reliable. Hence the need for objective measures in such trials.
To a lesser extent, it can also be argued that subjective measures are not ideal for all participants in this trial, including the control group. With graded activity-oriented therapies, which all the participants undertake (1), there may be response bias (6). This was seen in a review of three Dutch trials of graded activity-oriented cognitive behaviour therapy (CBT) for CFS. While the CBT participants reported improvements in fatigue (and also SF-36 physical functioning although that was not measured in all of the trials), no improvements in objectively measured activity were reported over the control group(7). Similarly a mediation analysis showed changes in physical activity were not related to changes in fatigue. A similar effect with CBT could be in PACE Trial, the largest such trial in the CFS field(8).
Although participants who had undergone CBT reported improvements in scores on both the Chalder Fatigue Scale and SF 36 physical function subscale, no improvements were reported in the six minute walking distance compared to the group who had undergone no additional individual therapy (all participants had specialist medical care). Similarly, CBT did not significantly reduce employment losses, overall service costs, welfare benefits or other financial payments(9).
Objective measures of physical activity are one type of objective measurement that could be employed. This could be used not just to measure the total quantity of activity but also to check the intensity of activity as people with ME/CFS may perform lower levels of more intensive activity(10). Tests of neuropsychological performance could also be used, given the impairments that have previously been reported(11). If necessary, a webpage could be created that could be accessed remotely.
One particular problem with the 0-33 scoring method for the Chalder fatigue scale is that patients can give unusually low, or artificially good, scores.
The scale consists of 11 questions. For each question (e.g. "Do you have less strength in your muscles?"), patients have to say whether they have the symptom: "Less than usual" (score of 0); "No more than usual" (score of 1); "More than usual" (score of 2) or “Much more than usual” (score of 3). So healthy people should score around 11 and indeed in the only population study I can recall that gave data for a healthy (no disease/current health problem) group, the mean was 11.2 (12).
However, some unusual scoring is possible. This was seen in a multiple sclerosis trial, of a similar CBT intervention to the graded activity-oriented CBT used in CFS (13). Participants in the CBT leg of the trial entered with a Chalder fatigue scale score of mean (sd): 20.94 (4.25). Two months after therapy, the mean (sd) was 7.90 (4.34) i.e. this groups suffering from multiple sclerosis had a much better score than one sees in healthy people!
Such averages could also hide non-responders or, possibly more seriously, people who deteriorated, depending on how the data was analysed. For example, if two participant deteriorated and ended up with a Chalder fatigue scale scores of 32, but 8 others had an average score of 2, this would give an average score of 8, again giving the impression that this group had less fatigue than healthy people. This issue of supranormal scoring with likert scoring (0-3) can be dealt with by utilising the commonly used bimodal scoring method for the Chalder fatigue scale. However, both it and likert scoring suffer from ceiling effects in CFS populations so other scales are likely preferable (14,15). If the Chalder fatigue scale is used, the original developers of the scale suggested, based on their analyses, that "it would probably be more useful to have two scores, one for physical fatigue and one for mental fatigue"(16).
(Message has reached word limit - references are reply)
Competing interests: I am the Assistant Chairperson and Information Officer for the Irish ME/CFS Association. All my work for the Association is voluntary.
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On 2014 Jul 09, Mathias Wellmann commented:
Comment regarding Kukkonen et al. Treatment of non-traumatic rotator cuff tears. A RANDOMISED CONTROLLED TRIAL WITH ONE-YEAR CLINICAL RESULTS, Bone Joint J 2014;96-B:75–81. PMID: 24395315
Dear Authors,
we read the study with great interest und discussed the clinical implications. We think the authors did a great job respecting formal aspects (prospectively randomized design, equivalent cohort size, homogeneous patient distribution). However, there are a few aspects of the study which are potentially misleading:
The title of the study is misleading or to general at best. A more precise title would be: Treatment of small, well compensated non-traumatic supraspinatus tendon tears. We think a study title should be as clear as possible and should especially answer the question: What issue was studied? The study of Kukkonen et al. exclusively investigated patients with small (<10mm) supraspinatus tendon tears, which were well compensated regarding range of motion (full range of motion, inclusion criteria). In its present form the title of the study may lead to a transfer of the results to patients with decompensated full-thickness tears of the supraspinatus tendon. Such transfer is not valid and should be prevented using a more precise study title.
All patients with an passive external rotation <30° and an elevation <120° were excluded from the study and the limitation of elevation and external rotation was defined as stiffness. However, a loss of elevation <120° is not a sufficient criterion to define shoulder stiffness. An adequate examination would have quantified passive glenohumeral abduction and external rotation (external rotation in comparison to the contralateral unaffected side). Further, the percentage of patients excluded because of shoulder stiffness should be indicated, since this is not a very common combination in patients with atraumatic rotator cuff tears. In the given form there is a risk that the study design systematically excludes patients with restricted range of motion caused by loss of strength and pain. This is a basic issue, since these are the typical patients, in which we think about rotator cuff refixation.
The type of supraspinatus-tears for the patients, that were included in the study should be clearly defined (full thickness versus partial thickness tears). The authors use the term „supraspinatus tendon tear comprising <75% of the tendon insertion and documented with MRI“. Thereby it is unclear, if partial articular und bursal sided tears involving <75% of the tendon substance were also included in the study. In the results section the authors indicate the sagittal diameter of the tears treated by surgery. Does that mean, that all tears were full-thickness tears?
It is unclear, if any of the patients had been treated by physiotherapy previous to the inclusion, or if this was an exclusion criterion as well. How did the authors deal with patients, that were randomized to be treated by surgery but did not agree to a surgical intervention.
The authors did not perform a follow up MRI or even sonography to determine the rerupture rate of the rotator cuff repairs. This would have been a substantial information estimating the clinical success of rotator cuff repair. If further follow up investigations are planned in the study design, we strongly recommend to perform MRI scans.
The Constant Score may not be the most helpful score with regard to outcome discrimination for a patient population with „ full range of motion“, since it strongly estimates range of motion (40 points) compared to pain (15 points) and the level of daily actvities (20 points). For such patients more detailed patient reported outcomes (PROs) should be beneficial.
We recommend to revise the marked aspects to reach the highest possible scientific impact for this publication.
Mathias Wellmann on behalf of the Shoulder committee of the AGA - Society for Arthroscopy and Joint Surgery
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On 2014 Jun 18, Gauthier Bouche commented:
We would like to thank the authors for carrying out this very important update and for emphasizing that patients with locally advanced rectal cancer should be informed of the lack of consensus about adjuvant chemotherapy after preoperative chemoradiotherapy. As the authors point out in their discussion, ’the control of occult distant disease is becoming a major objective in treatment strategies’. They indicate upfront chemotherapy as one relevant option being tested in a large randomised trial (PRODIGE 23). Our international collaborative group interested in ‘financial orphan therapies’ - i.e. therapies with high clinical but no or low commercial value - has identified over the years several therapeutic options that we think could prevent distant metastasis in patients with locally advanced rectal cancer. We would like to list three promising strategies supported by clinical and biological evidence. These strategies carry a low toxicity risk, are low cost and are easy to administer.
Cimetidine is an H2-receptor antagonist which has been used for decades as an oral drug in the prevention and treatment of gastro-duodenal ulcers. Cimetidine has demonstrated a strong anticancer effect (Kubecova M, 2011) that is unlikely to be explained by one single mechanism. Amongst other things, cimetidine inhibits cancer cell adhesion via E-selectin inhibition (Matsumoto S, 2002), increases the antigen-presenting capacity of dendritic cells (Kubota T, 2002), increases lymphocyte infiltration in tumours (Lin CY, 2004) and reduces accumulation of myeloid-derived suppressive cells (Zheng Y, 2013), which may all contribute to the clinical findings in colorectal cancer patients. A 2012 Cochrane Meta-Analysis reviewed the five randomised trials performed in colorectal cancer patients and concluded that ‘cimetidine appears to confer a survival benefit when given as an adjunct to curative surgical resection of colorectal cancers’ (Deva S, 2012). The main unanswered question is duration of treatment. The randomized trial currently ongoing in 120 colorectal cancer patients in New-Zealand and Australia (ACTRN12609000769280) which aims to look at the effect of perioperative cimetidine should answer this question. Recruitment in this trial has been completed and 45% of all patients have a primary rectal cancer (http://meetinglibrary.asco.org/content/122801-143).
Polysaccharide-K (PSK) is isolated and purified from the cultured mycelium of the Basidiomycete Coriolus versicolor. It was first approved as an oral anticancer drug in Japan in 1976 under the name of Krestin® and its use has been restricted to colorectal, gastric and small-cell lung cancer after re-evaluation by the Japanese authority in 1989 (Maehara Y, 2012, Fujiwara Y, 1999). Several randomized trials of various quality have been performed over the past four decades in Japan which overall indicate a benefit in colorectal cancer patients (Maehara Y, 2012). The drug is now available as a generic in Japan (Fujiwara Y, 1999). The most critical question is whether similar outcomes would be found in a non-Japanese population. Since this therapy has shown excellent safety and is already commercially available in Japan, this question could be easily tested in randomized trials. Mechanistically and according to the wealth of literature available from Japanese researchers, PSK seems to have multiple mechanisms of action, from direct anticancer activity to immune-mediated effects (Maehara Y, 2012). Obviously, any project or trial outside of Japan should involve Japanese clinicians and researchers experienced with PSK.
Ketorolac is a Non-Steroidal Anti-Inflammatory Drug (NSAID) approved in the EU and in the USA and available for injection in the management of postoperative pain. In 2010, Forget et al. found in a retrospective study that breast cancer patients undergoing mastectomy who had received one single injection of ketorolac during surgery had a 63% reduction in the risk of recurrence compared to patients who did not, even after adjustment for known confounders (Forget P, 2010). This association was confirmed in patients receiving either ketorolac or diclofenac and undergoing breast-conserving surgery (Forget P, 2014), as well as in patients undergoing lung cancer surgery (Forget P, 2013). The work from Ben Eliyahu’s group provides a biological rationale for this, even though Ben Eliyahu used etodolac in combination with propranolol and the design of the mice experiments is different from the human observations (Benish M, 2008). Retrospective data in colorectal cancer patients should be available soon from the group of Patrice Forget (personal communication) and will hopefully further support this hypothesis. The potential benefit of perioperative administration of ketorolac will have to be balanced against a potential risk of anastomotic leakage. A meta-analysis of randomized trials indicates a non-significant doubling of the risk (2.4% in patients not receiving NSAID vs. 5.1% receiving NSAID within 48 hours of surgery Burton TP, 2013), but such increase has not been observed when only one single dose of NSAID was administered. This will however need to be taken into consideration when designing a trial of perioperative ketorolac in colorectal cancer patients.
We can deduce from the Bosset et al. article that there is an early peak of recurrence in the first two years, as more than 50% of the DFS events occurred during this period. This is in line with data from DeMicheli for breast (Demicheli R, 2010) and lung (Demicheli R, 2012) cancer and is another argument to target the perioperative period with drugs such as NSAID or cimetidine to prevent recurrence (Demicheli R, 2008).
There are other options which could be considered. However, the strategies we propose have a common theme. Our goal is to address the fact that the perioperative period is one that is characterized by a systemic immune and pro-angiogenic milieu that is found in a typical wound healing response. Such a response is characterized by a post-operative surge of cytokines and growth factors into the systemic circulation that may awaken dormant micrometastases, thus accounting for the early recurrence pattern seen following surgery for many types of cancer (Retsky M, 2013). Thus short-term perioperative treatments aimed at countering such a response could have long-term beneficial consequences. Finally, these treatment options represent low-hanging fruits which, if their efficacy were to be proven in trials, could be rapidly implemented in practice in most places in the world with minimal toxicity and at a reasonable cost. We sincerely hope to see others supporting this type of research.
Gauthier Bouche, Anticancer Fund, Strombeek-Bever, Belgium
Pan Pantziarka, Anticancer Fund, Strombeek-Bever, Belgium & The George Pantziarka TP53 Trust, London, UK
Lydie Meheus, Anticancer Fund, Strombeek-Bever, Belgium
Patrice Forget, Department of Anesthesiology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium
Vidula Sukhatme, GlobalCures, Inc; Newton MA 02459, USA
Vikas P. Sukhatme, GlobalCures, Inc; Newton MA 02459, USA & Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
The authors declare that they have no competing interests.
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On 2014 Mar 24, Karen Woolley commented:
FINALLY...more attention is being paid to PRACTICAL issues about data sharing!
Well done to Wilhelm, Oster, and Shoulson for reminding us that it takes resources (financial and nonfinancial) to share data. We should also remember that it takes resources (financial and nonfinancial) to publish data. This issue seems to have been lost in the hand-wringing taking place over low and slow publication rates.
A robust systematic review, presented at the 2013 Peer Review Congress (organised by JAMA and the BMJ) identified “lack of time” as the main reason why researchers don’t write up manuscripts.<sup>1</sup> Clearly, many researchers need writing support (ie, from legitimate, ethical, highly trained and qualified professional medical writers; NOT ghostwriters). Similar to Wilhelm et al., we outlined the need to consider the cost issue if we want to enhance publication speed and quality.<sup>2</sup> We think our paper struck a chord - it was among the top 5 most downloaded papers from Current Medical Research & Opinion that year.
Professional medical writers are trained to help make complex data understandable to different target audiences (eg, researchers, regulators, patients) and could, therefore, help address another critical point made by Wilhelm et al., “Standardization costs for data-sharing models include the additional effort required to share, beyond what is required of any high-quality clinical research, because it takes considerably more effort to organize and make data understandable to others.”
Wilhelm et al. conclude that “Understanding and planning for the costs [for data sharing] at the outset of research can help realize the full potential of data sharing.” The same sentence could apply to publications ie, understanding and planning for the costs of manuscript writing at the outset of research can help realise the full potential of peer-reviewed publications.
Authors and affiliations Karen L. Woolley PhD CMPP,a Art Gertel MS,b Cindy Hamilton PharmD,c Adam Jacobs PhD,d Jackie Marchington PhD CMPPe (Global Alliance of Publication Professionals; www.gappteam.org) a. Division Lead. ProScribe – Envision Pharma Group; Adjunct Professor, University of the Sunshine Coast, Australia. b. VP, Regulatory and Medical Affairs, TFS, Inc.. USA; Senior Research Fellow, CIRS. c. Assistant Clinical Professor, Virginia Commonwealth University School of Pharmacy; Principal, Hamilton House, USA. d. Director, Dianthus Medical Limited, UK. e. Director of Scientific Operations, Caudex Medical, UK.
Disclosures All authors declare that: (1) all authors have or do provide ethical medical writing services to academic, biotechnology, or pharmaceutical clients; (2) KW’s husband is also an employee of ProScribe – Envision Pharma Group; all other authors’ spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (3) all authors are active in national and international not-for-profit associations that encourage ethical medical writing practices. No external sponsors were involved in this study and no external funding was used.
References 1. Scherer RW, Ugarte-Gil C. Authors’ reasons for unpublished research presented at biomedical conferences: A systematic review. http://www.peerreviewcongress.org/abstracts_2013.html#1 Accessed 27 February 2014. 2. Woolley KL, Gertel A, Hamilton C, Jacobs A, Snyder G (GAPP). Poor compliance with reporting research results – we know it’s a problem…how do we fix it? Curr Med Res Opin 2012;28:1857-1860.
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On 2015 Apr 24, BSH Cancer Screening, Help-Seeking and Prevention Journal Club commented:
The HBRC journal club read Scherer et al’s paper with interest. While flu vaccination is not the focus of our work, using metaphors as a manipulation to increase the likelihood of a behaviour and the methods used to test the efficacy of doing so, resonated with our research team. Most of the group were unfamiliar with the metaphor literature and found the introduction to provide a useful summary of the field. The authors present a discussion of the role of risk perceptions and affect, but a more detailed discussion of how the two interact and their complexities might have provided a truer representation of the field.
The group liked that the authors attempt to measure whether participants were likely to move beyond intention (measuring participants’ desire to receive a reminder email to get a flu vaccination), without having to measure behaviour (which is difficult to do objectively). However, contrary to the authors, the finding that individuals who occasionally get a flu vaccine were more likely to request an email reminder was unsurprising to us because individuals who always get a flu vaccination seemingly do not need reminding. A further strength of the paper is that non-emotive metaphors were considered (the flu as a weed), as this helped dispel the suggestion that the effect was due to vividity or violence (as might be the case with metaphors such as ‘beast’ and ‘riot’). The group wondered if a virus could also be considered to be a metaphor, given its use in computing. Additionally, it may have been of interest if the vaccination itself was also part of the metaphor, for example the flu virus being described as a ‘weed’ and the flu vaccine as ‘weed killer’. In Hauser DJ, 2015 using congruent metaphors to describe an illness and the measure to prevent the illness increased behavioural intentions compared to just using a metaphor to describe the illness.
While metaphors may increase the vividness of the flu and encourage individuals to engage, the group were concerned about how use of metaphors to manipulate behaviour may not be congruent with informed decision making, instead being considered coercive. We disagreed with the authors suggestion that metaphors might have a use in decision aids, which we believe have a role in helping individuals make informed decisions and not swaying their opinion. We suggested that metaphors might be useful when the aim is to increase individuals’ understanding, rather than increasing intentions to engage in a behaviour. It may also be important to consider the unintended consequences of using metaphors, for example in the cancer field (the focus of our work), describing cancer as a battle may lead to suggestions that people who do not survive the disease did not fight hard enough. However, we acknowledge that metaphors are used ubiquitously in the media, which is difficult to control.
The group felt that flu vaccination was a complex example to choose to conduct these studies. Flu is a fairly common illness, which might result in participants having an accurate estimate of their risk of contracting the illness or how serious it is. This might explain why the manipulation did not affect the mediators in the main analysis. Individuals are likely to have existing beliefs about vaccination (for example, beliefs about side effects, effectiveness) and the benefits of vaccination might not always be obvious (the individual does not contract the flu - a non event and herd immunity benefiting the population). It would have been helpful to have been informed about the flu vaccination recommendations in the USA where the study was conducted. Cultural differences in how the flu is appraised, treated and prevented between countries might alter the effect of metaphors. For example, in the group’s opinion, the metaphor ‘beast’ was an exaggerated conceptualisation of the flu and felt removed from the actual consequences of the virus.
Study 3 was perceived by the group to be the most useful study of the paper as it used a validated measure of affect and a larger sample than Study 1. The ecological validity of studies 2 and 3 could have been increased if Study 1 had been a ‘think aloud’ study, whereby the authors could have gained a justification for the mediators of flu vaccination that were tested. The group thought that a strength of the studies is that the authors did consider the possible mediators of any effect of the metaphor. Other mediators that could have been considered include attitudes and a measurement of arousal (engagement). A ‘think aloud’ study might also help to ensure that metaphors are used appropriately, for example in Hauser DJ, 2015, use of an enemy metaphor reduced intentions for self-limiting cancer prevention behaviours (such as stopping smoking or limiting alcohol intake). The group also wondered how novel the ‘novel’ metaphors used in the studies actually were, something that pilot work could have investigated.
The group thought it was interesting that the findings were not wholly consistent across the studies reported and considered that this could have been a product of differences in the sample. The authors do not describe whether participants were randomised to each condition, and no baseline measurements were reported, both of these factors leave readers unclear about whether the sample was similar across each of the studies. It would also have been helpful to have a justification for the sample size chosen for each of the studies.
Scherer et al. present a novel paper, which has provided readers with examples of how to measure the impact of using metaphors to increase intentions to receive a flu vaccination. Future work in this field should consider conducting pilot work to ensure the topic, manipulation and measures used are relevant to the population of interest. We caution readers to consider the unintended consequences of using metaphors to manipulate behaviour, including concern about the ethical implications this might have.
Conflicts of interest We report no conflict of interests and note that the comments produced by the group are collective and not the opinion of any one individual.
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On 2014 Aug 06, Xudong Fu commented:
Thanks for your comments. It is really interesting. I hope I could explain why I don't think alpha-ketoglutarate works as an antioxidant to extend lifespan.
It has been shown that α-ketoglutarate is an antioxidant. However, antioxidants are not necessarily able to extend lifespan. Actually, the relationship between ROS and lifespan has not been established. Increase of ROS may contribute to lifespan extention potenially through downstream defensim activation and overexpression of antioxidant enzyme is not able to extend lifespan in mice (http://www.sciencedirect.com/science/article/pii/S0092867413006454, http://onlinelibrary.wiley.com/doi/10.1111/j.1474-9726.2008.00449.x/full).
Our paper discovers that α-ketoglutarate can bind and inhibit ATP synthase and extend lifespan in C. elegans. The inhibition of ATP synthase is actually likely to generate more ROS. It has been shown that oligomycin, a known ATP synthase inhibitor, could induce ROS in vivo. In our hand, we also find that α-ketoglutarate could induce ROS (by DCFDA dye measurement) both in C. elegans and cells. That suggest α-ketoglutarate is unlikely to increase lifespan simply through antioxidant function. It's more likely α-KG regulates lifespan through induction of ROS instead. We actually have explained why we don't think ROS plays a major role in the life extension effect for α-ketoglutarate; see Supplementary Information (http://www.nature.com/nature/journal/v510/n7505/extref/nature13264-s1.pdf). Briefly speaking, although α-ketoglutarate could induce ROS, additional antioxidants does not decrease the lifespan extension effect of α-KG in our hands. In addition, ROS has been suggested to activate TOR but we observed α-ketoglutarate decrease TOR.
In terms of the dosage we used, it has been known that α-KG is not highly membrane permeable. To solve this issue, we made octyl α-KG, an ester form of α-KG which is more membrane permeable. After octyl α-KG goes into the membrane, it gets hydrolyzed and releases free α-KG. Most of the assays in Fig. 2 were done with octyl α-ketoglutarate instead of original α-KG. That's the main reason we don't need to use 8mM dose for Fig. 2 assays. We also tried octyl α-KG in lifespan assays (see Extended Data Table 2). It only required micromolar scale of octyl α-KG instead of millimolar for us to observe the lifespan extension. In addition, after treatment of 400 uM of octyl α-KG on cells or after treatment of 8mM α-KG on C. elegans, the in vivo concentration of α-kG increased comparably around 50-100%. That suggest 50-100% increase of endogenous α-KG could inhibit ATP synthase and extend lifespan, nonetheless the different forms or concentration of α-KG we used, consolidating our hypothesis that α-KG extend lifespan through direct ATP synthase inhibition. Also, because the endogenous increase of α-KG is only 50-100%, this concentration does not seem to be in line with the concentration suitable for non-enzymatic reaction.
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On 2014 Aug 04, Paul Brookes commented:
This paper addresses a very important point... namely, one of the proposed mechanisms by which ischemic preconditioning (IPC) is thought to bring about cardioprotection. It has been hypothesized that increased leakiness of the mitochondrial membrane to protons may lead to a lowering of ROS generation. We provided some evidence to support increased H+ leak in IPC in 2006 Nadtochiy SM, 2006. Unfortunately, it's not immediately clear to me exactly how the authors measured H+ leak in this study, and also whether their ROS measurements were performed correctly.
First proton leak: The normal way this is determined is to make simultaneous measurements of membrane potential and respiration in a single chamber equipped with an oxygen electrode and another electrode sensitive to a lipophilic cation such as TPP+. The authors are to be commended on their choice to use a TPP+ electrode, which instantly makes this paper more quantitative than others using qualitative fluorescent probes such as TMRE. They measured membrane potential (as reported in Figure 3) using succinate as a substrate for complex II, with rotenone to inhibit complex I. All good so far. However, normally oligomycin is added to inhibit the ATP synthase as a potential source of leak. In addition nigericin is added to equilibrate K+/H+ and thus ensure the potential is a measure of protonmotive force. As such, the potential measured here was not in a true state 4 condition which is typically required for quantitation of proton leak.
After describing membrane potential measurements, the methods section describes respiration and H+ leak methodology. It appears oligomycin was added this time (good!), but then something very odd happens... it is stated that "H+ leak was measured as the state 2 respiration rate required to maintain membrane potential at -150mV". Nowhere is it stated how that value of 150mV was arrived at. Normally, when doing these measurements, you set the mitochondria in state 4 (succinate, rotenone, oligomycin, nigericin), and then titrate the activity of the respiratory chain with an inhibitor such as malonate. Step-wise titration then gives you a series of membrane potential and respiration traces, a curve, from which the leak rate at any given potential can be read off. The question is, if such curves were made, how were they made (no mention of malonate anywhere), and why aren't they shown in the paper? The scary alternative explanation may be that they "measured" leak by imposing the 150mV membrane potential by titrating in uncoupler. This is incorrect - you can't add something that changes the leak as a way of measuring the leak. The other odd thing is that the average baseline membrane potential in the IR group barely above 150mV, so some replicates in that group must have had a potential value below 150mV to begin with. How did they authors get those mito's UP to 150mV for the leak measurement? Overall, it would be a whole lot better if they just showed the full leak curves.
What about ROS? The problems here are two-fold. First it appears that SOD was not added to the incubations to scavenge any stray superoxide and turn it into H2O2 for the assay to pick up. Second, the calibration of the assay was performed incorrectly. It is stated in the methods that the signal was calibrated by "adding known concentrations of H2O2 to buffer solution containing horseradish peroxidase and Amplex-Red" The problem is, it is necessary to calibrate in the presence of mitochondria, so the signal you measure with the calibrating H2O2 is under the same condition as the measurement itself. The way this is commonly done is to just add a bolus of H2O2 at the end of each run. This has the advantage of making every run internally calibrated, which cuts down on noise (this is a very noisy assay). The outcome here is a bit odd... the values of H2O2 generation are in the range of 10-40 nM/min/mg protein. Ignoring the odd units (rates of things should be expressed in moles not Molar), let's assume they meant to write nmols/min/mg - that would put their rates about 1500-fold greater than typical for these conditions (e.g.Chen Q, 2003).
So, TL/DR - good ideas, but more info' is needed on the proton leak method, and the ROS numbers are just wild. Also, lest anyone think I'm attacking this work because I happen to be one of the people who originally proposed proton leak --> lower ROS --> protection in IR injury, that's not the case. In-fact, my lab' is now pursuing a completely different downstream signaling mechanism, as a mediator of the protective effects of mitochondrial uncoupling, so if the results of this paper are true, my life just got a whole lot easier! I just want to be sure before I start citing it.
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On 2014 Oct 18, David W Brandes, MS, MD, FAAN commented:
I am very happy to see more published information about this topic. I have been speaking professionally abut this topic for 10 years and it is becoming increasingly recognized as to it's importance in the management of MS patients. This article confirms the often unrecognized frequency of this issue. When MS patients say they "are tired all the time," we need to think about the details. Physical fatigue, cognitive fatigue, psychological fatigue (depression) and sleepiness may all be part of this complaint.
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On 2015 Sep 17, Ghassan El-Baalbaki commented:
authors of this comment are: Loose, T.<sup>1,3</sup> , Ashrah, L.<sup>1,</sup> Romero, M.<sup>1,</sup> Bégin, J.<sup>1</sup> and El-Baalbaki, G.<sup>1,2</sup> Affiliations, Université du Québec À Montréal<sup>1,</sup> McGill University<sup>2,</sup> Université de Nantes<sup>3</sup> .
In this study, the authors examine the efficacy of Acceptance and Commitment Therapy (ACT) in treating partner aggression. After entering into communication with the first author, she confirmed that this study corresponds to her doctoral thesis (Zarling, 2013). We read her thesis in order to gain further knowledge about the published study, and we found two important aspects of the work that need to be brought into light: 1) we find it difficult to conclude that partner aggression was specifically reduced, because of threats to internal validity. 2) There seems to be inaccuracies in their statistical calculations.
The primary objective was to demonstrate that ACT reduces intimate partner aggression better than the placebo control group. The authors strongly suggest that ACT was indeed able to do so. However, several points call this statement into question.
First of all, it is worth noting that partner aggression is never specifically assessed. One may think that the Conflict Tactics Scales-2-Physical Assault Scale (CTS-2) did assess this construct (Straus, Hamby, Boney-McCoy & Sugarman, 1996), but when taking into account the exact content of the administered questionnaire that was figured in her thesis, it can be seen that the instructions were modified in order to include aggression towards “people we care about” (Zarling, 2013, p.132) instead of specifically towards a partner. This modification is not mentioned in the published article. Hence, participants could have hypothetically committed aggressive acts exclusively towards a non-partner, such as a child or a friend. It is thus hard to conclude that aggressive behavior, specifically among couples, decreased as a result of therapy.
Furthermore, after modifying the instructions, one of the items even became incoherent. More specifically, when taking into the modified instructions of the questionnaire, the item stated “When upset or in a disagreement with someone you care about … have you became angry enough to frighten your partner?” (italics added)(Zarling, 2013, p. 132). It seems that this question was destined to ask if the participant became angry enough to frighten someone that they « care about » and not their « partner ». For example, if the participants were (or became) single, they could have interpreted this question as if they were angry enough to frighten someone that is not necessarily their partner. It is unclear how the authors wanted the participants to interpret this item. The way that the construct of partner aggression was assessed calls into question the internal validity of the study.
It remains questionable why the authors neglected to assess attrition of couples during the study. Over the course of the study, it is possible that aggressive behavior decreased more in the ACT group as a result of more couples breaking up in this treatment condition than in the placebo control group. Even if the authors carried out both completer analysis and intent to treat analysis and the results did not differ on measured variables, the attrition of couples was not measured. Hence, it is impossible to know if the groups differed on partner attrition. It remains possible that participants continued to aggress former partners, but again this cannot be asserted simply because it was not measured. Assessing partner attrition would have helped neutralize a pertinent threat to internal validity. Hence, internal validity was limited by not taking into account partner attrition.
Lastly, it is worth bringing up that the first author and two other investigators co-led all administered interventions (p. 201). Even if the authors state this in their article, after looking at the detailed explanation of the recruitment process of investigators, this choice does not seem to be justified. It seems that the first author was able to recruit investigators at no extra cost and it is questionable as to why she did not recruit three instead of two, thus avoiding a potential threat to internal validity. The explanation provided in her thesis, but not the article, also states that all the manipulation checks were carried out by the first author and supervised by the second and third authors (Zarling, 2013, p.61). Because of the implication of the authors in the experimental procedure, the results are potentially attributable to the experimenter expectancy effect. This is another threat to internal validity that evokes the tendency for researchers to unintentionally bias the results of their investigations in accord with their hypotheses. In taking into account the previously stated points, it seems difficult to conclude that this study shows that ACT specifically reduces partner aggression better than a placebo control group.
On another note, the statistical validity of the study can be questioned:
Throughout the results section of the paper (pp. 205–207), the authors report many beta values (β) for intercepts and slopes. If these are indeed beta values, they should vary between approximately 1 and -1 (Cohen, Cohen, West & Aiken, 2002). However in many cases, reported values are outside of this range. For example the authors state “The ACT participants also reported significantly less psychological aggression, β = 2.05, SE = 0.71, t(97) = 8.33, p < .001, and physical aggression, β = 2.21, SE = 0.65, t(97) = 8.19, p < .001, at the 6-month follow-up assessment” (p. 8). This leads us to think that the authors are actually reporting non-standardized coefficients (B) because B values can vary outside of this range. However, if this is the case, then the t values reported become incoherent. t values should equal B/(2SE) (we retained the value of 2 after rounding up from 1.96 which corresponds to 95% of a normal distribution (Christensen, 1986)), but reported t values do not correspond to this calculation. For example, let’s take another look at the previous citation and assume that it actually refers to B values. According to our calculations, t = B/(2SE) = 2.05/(2*0.71)=1.44, but the authors report that t = 8.33, p < .001. More simply stated,if the authors are indeed reporting β values, then many of the β values seem to be impossible (outside of the ± 1 range), but if they are reporting B values, the t values seem to be impossible according to our calculations. We were wondering how these seemingly paradoxical results could be explained.
In conclusion, even if this research topic is of great interest, two main points should to be taken into account. First of all, it is hard to state that ACT is an effective treatment to reduce partner aggression because 1) partner aggression was never specifically assessed 2) partner attrition was not measured 3) of potential bias due to the experimenter expectancy effect. Secondly, it is hard to draw conclusions from the statistics figured in the study because 1) if β values were indeed being reported, then they lie outside of the ± 1 range and 2) if B values were actually reported, then the t values become incoherent.
References
Christensen, H. B. (1986). La statistique: démarche pédagogique programmée. Boucherville: Gaëtan Morin.
Cohen, J., Cohen P., West, S. G. et Aiken, L. S. (2002). Applied multiple regression/correlation analysis for the behavioral sciences. New York: Routledge.
Straus, M. A., Hamby, S. L., Boney-McCoy, S., & Sugarman, D. B. (1996). The revised conflict tactics scales (CTS2): Development and preliminary psychometric data. Journal of Family Issues, 17, 283–316.
Zarling, A. (2013). A preliminary trial of ACT skills training for aggressive behavior. University of Iowa.
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On 2015 Jul 15, Raphael Levy commented:
Thanks Harald for commenting on my blog post about SmartFlares / Nanoflares with reference to this paper.
I reproduce the conversation below. I hope it continues and others join in.
Raphael
"Hi everybody, as the correspending author of a Stem Cell paper in which we have used the SmartFlares on different pluripotent cells of human, murine and porcine origin I want to reply to two of the above mentioned questions.
Why do we see a signal at all in the scramble control? I think one cannot expect a negative control which does not produce a fluorescent signal at all. The fluorophore may not be quenched by 100% and may be subject to degradation, especially when applied for a longer time (two days or more). Nevertheless, within 16 to 24 hours after the application of the nanoparticles we see a clear-cut difference of fluorescence intensity when comparing scramble control and gene-specifc Smart Flares. http://www.ncbi.nlm.nih.gov/pubmed/25335772
We believe that this difference is reliable and specific. We have selected freshly reprogrammed murine iPS cells based on their Nanog-specific fluorescence intensity in situ. In downstream experiments we could confirm that only colonies with a high fluorescence intensity expressed higher amounts of endogenous pluripotency factors and showed a superior capacity to differentiate. Therefore, we belive that these functional data strongly support the idea that the fluorescence intensity was indeed correlated to a specific interaction with the Nanog mRNA in these clones.
Why do different cells take up varying amounts of SmartFlares? I think this difference is not surprising as the nanoparticles are engulfed by endocytosis. This process is influenced by the cell type, the differentiation status and the cellular ability to perform phago- and macropinocytosis. Therefore, we think that a uniform uptake rate cannot be expected."
I replied "Hi Harald
Thanks again for commenting here and sorry for the delay in replying. It is interesting that you see some differences but the big question that remains is how could the technology possibly work?
It can only work if the particles escape endosomes, but: 1) there is no reason why they should, 2) this problem is not discussed in the original publication introducing the technology, 3) there is no direct evidence in the literature that it happens, and, 4) all the data we are accumulating indicates that the particles are indeed in vesicular compartments (more on this soon on the open notebook as we have just had our cell electron microscopy results this week).
The images shown in your articles are low mag overviews of many cells and therefore the resolution does not allow to discuss any cellular localization. Do you have any higher resolution images that you could share? Do you have any (direct) evidence and/or proposed mechanism for endosomal escape?
The unequal distribution of uptake (cell to cell variability) is also a big concern. I don鴠believe that it relates to differences between rate of uptake of different cells. Such differences would average over an 18 hour period and they should also be seen in the dextran uptake. A possible interpretation would be some degree of nanoparticle association/aggregation before interaction with the cells (this is to be tested experimentally).
Raphael"
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On 2015 Nov 30, John P A Ioannidis commented:
Dear Joshua,
thank you again for your comments. I am worried that you continue to cut and paste to distort my sentences.
- The headline over my text was written by the Nature editors as their introduction to the paper, so perhaps you should blame them and ask them to replace it with "Here follows a horrible paper by Ioannidis". Yet, I think you would still be unfair to blame them, because their headline says "most innovative and influential", not just "most innovative". The terms "influential", "influence", "major influence" pervade my paper multiple times, but you pick one sentence with "innovative" instead, and interpret it entirely out of its context.<br>
- The phrases "the most important" and "very important" are not identical. Very important papers may not necessarily be THE most important. But they are very important - and influential. [As an aside, honestly, this repeated cross-examining quotation-comment style makes me feel as if I am answering the Spanish Inquisition. Am I going to be burnt at the stake now (please!) or there is one more round of torture?]
- We agree we need evidence, more evidence - evidence is good, on everything, including the current NIH funding system, which has practically no evidence that it better than other options, but still distributes tens of billions of dollars per year. Wisely, I am sure.<br>
- "your list contains...". This is not my list. This is the Scopus list. Right or wrong, I preferred not to manipulate it. Your colleagues did manipulate it and did not even share the data on how exactly they manipulated it.
- You continue to use the term "innovative thinker" out of its context. I scanned again carefully my paper and I can't find the word "excellent". In my mind, a student who has authored as first author a paper that got over 1000 citations (and the paper is not wrong/refuted) is already worthy to be given a shot as a principal investigator. If you disagree, what can I say, feel free not to fund him/her. And please don't worry, most of these guys are not funded anyhow currently, many of them even quit science. Hundreds of principal investigators who publish absolutely nothing or publish nothing with any substantial impact get funded again and again. Hurray!<br>
I am afraid it is unlikely there will be more convergence in our views at this point. A million thanks once again, I have learnt a lot from your comments.
John
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On 2015 Sep 06, Lydia Maniatis commented:
The claims of Blakeslee and McCourt are flawed on logical, methodological, theoretical, and empirical grounds.
Perhaps the core error is the denial of perceptual facts, as described below (and as noted also by Gilchrist in his commentary on this article).
In the Adelson checker-shadow illusion (to take one example), a check in apparent shadow looks white, while an equiluminant check, apparently in plain view, looks black. Aside from the additional presence of the apparent shadow, the experience of the two surfaces is similar to looking at a white check and at a black check under homogeneous illumination. Kohler (1935), describes a “real-world” version wherein a white and a black paper appear white and black, respectively, even if the illumination is adjusted so that the two surfaces are actually equiluminant.
Imagine, now, what would happen if we asked a naive observer to report on “the intensity of the light coming from the surface of each of the two checks.” First, he or she would likely assume the question referred to the apparent illumination of the surfaces. In this case, the white, “shadowed” check should receive a lower rating than the black “plain-view” one. If we then tried to clarify that we want the observer to make matches based on “the amount of light each surface is sending to the eye,” (its luminance) I think the observer would have trouble a. understanding what we are asking and b. performing the required task. And I'm not sure anyone would be able to judge, with confidence, whether the two checks in the Adelson checkerboard are, or are not, in fact equiluminant. That's what makes the demo so impressive. Even if observers could estimate this value, the task would be difficult and the results unreliable. To achieve it, they would have to focus narrowly on each square, isolating it from the surround.
Yet, Blakeslee and McCourt maintain that the latter task, which requires viewers to overide their spontaneous, salient perceptual experience, is “strictly based on appearance,” while the former, effortless experience is “based on an inferential judgment.” If, however, we define “appearance” as “what something looks like,” then the authors' arguments are obviously false, as can be confirmed by any observer.
The authors' argue that the experience which is quite literally based on appearance, is actually a product of learning. This is a major claim (implying that learning can actually alter a percept from black to white), but the authors offer no evidence for it. All of the arguments and available evidence is against. As Gilchrist (2015) points out, even fish seem to naturally achieve this kind of learning. A child can see the Adelson checker-shadow effect as effortlessly as an adult. Our perceptions aren't affected by what we learn about the nature of light and the properties of surfaces, we don't have to learn how to judge when a surface is in shadow or merely darker than its neighbor, or when it is covered by various types of transparency, we don't even have to learn that at night things don't actually change color. Given the difficulty scientists have in analyzing and modelling percieved lightness, and given that massive, early exposure to artificial images mimicking illumination variation has no discernible effect on our perception of the “real” world, the claim that people go through a process of learning to make the inferences necessary to achieve veridical percepts in natural conditions does not seem credible. B and M have certainly not tested it.
The quality that the authors argue is “strictly based on appearance” is a quality that they term “brightness,” defined as the perceptual correlate of luminance. The view that there is a perceptual correlate of luminance seems to be uncontroversial among lightness researchers (e.g. Kingdom, 2011; Gilchrist, 1999)), although Anderson (2014) seems to define brightness (more properly, in my opinion) as apparent illumination. The claim seems easy to refute.
Suppose we observe a set of surfaces lacking cues to differential illumination, and that some appear white, some gray, some black. Suppose, then, that we observe the same set of surfaces, at a different time, under a different degree of illumination. Assume that have completely forgotten the previous experience with the surfaces, and are again asked to judge their white/gray/black character. Our responses will typically be similar to those we gave in the first (now forgotten) instance. In other words, even though the illumination (and consequently the luminance) of the surfaces will have changed, our responses will remain the same. If the range of luminances is complete enough, they will, in both cases, be correlated with reflectance and not with luminance. Thus, even under homogeneous illumination, we cannot say that we are perceiving luminance, or that perception is more direct than in other situations. As always, the percept is the product of a complex visual process based on luminance values and structural assumptions.
When it comes to the case of non-homogenous (apparent) illumination, the authors seem to be treating illumination boundaries as though they were directly-perceived facts serving to support “inferentially” perceived lightness judgments. They say, for example, that “when the illumination component is clearly visible” the observer can use “brightness contrast” at the boundary to infer the magnitude of the illumination. There are a number of problems with this description.
First, if a shadow is perceived – is “clearly visible” - as the cause of the luminance boundary, then viewers are perceiving a double-layer – a surface with lightness x and an apparent shadow of darkness y lying on top of it. They are not perceiving a single “brightness” value. The authors are using the term “brightness” when they actually mean luminance.
Relatedly, the illumination boundary only becomes “clearly visible” after the visual process has inferred its presence based on the luminance structure – including the relative luminances at luminance boundaries - of the image. Whether the darker side of an edge will be perceived as being similar in reflectance, but lower in illumination than its neighbor, or as darker than its neighbor due to a lower reflectance, or any other combination of possibilities, depends on the global structure of the image. Given certain conditions, even a non-existent luminance edge may produce an apparent lightness difference, as in the case of illusory surfaces. So the argument that perceiving a surface as continuing beneath a “shadow” boundary is more inferential than perceiving a particular surface as gray due to its luminance relative to other surfaces in an image is naive. If “appearance-based” means “based on luminances”, then all perception is appearance-based. If it means that surfaces are perceived based on local luminance conditions, then it never is. Local conditions do not even determine photoreceptor activity in the horseshoe crab.
As corroborating evidence, the authors point to a few references, including Blakeslee and McCourt (2008), which is supposed to prove the existence of “brightness” judgments. Their stimuli consist of the classic simultaneous contrast demo plus variations that create weak impressions of differential illumination. The “brightness” judgments are defined as those that arise when observers are instructed to focus narrowly on the targets. This is similar to applying a mask. Effectively, we are talking about the same visual process acting on a different stimulus, not about a different type of judgment. Due to the weakness of the structural cues to differential illumination in B and M's (2008) stimuli, the ability of observers to isolate the target in this way is very easy. The demand would be much more difficult, and the results surely very different, if the stimulus had been the Adelson checkerboard.
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On 2016 May 23, Stanton A Glantz commented:
In June 2015 we published our paper “The smoking population in the USA and EU is softening not hardening” in the journal Tobacco Control. We showed that as smoking prevalence has declined over time, quit attempts increased in the USA and remained stable in Europe, US quit ratios increased (no data for EU), and consumption dropped in the USA and Europe. These results contradict the hardening hypothesis which is often used as part of the tobacco industry’s strategy to avoid meaningful regulation and protect its political agenda and markets, claiming that there is a need for harm reduction among those smokers who “cannot or will not quit.” Indeed, rather than “hardening” the remaining smoking population is “softening.”
In February 2016 we received an email from Robert West, editor of the journal Addiction, informing us that Addiction was about to publish an article by Plurphanswat and Rodu entitled “A Critique of Kulik and Glantz: Is the smoking population in the US really softening?” whose sole purpose was to critique our Tobacco Control paper, and offered to let us respond to the criticism.
The fact that Plurphanswat and Rodu sent their paper to Addiction was unusual because normal scientific procedure would have had them sending a letter to the editor of the journal that originally published the work (Tobacco Control).
As detailed below, we did respond, noting that Plurphanswat and Rodu’s paper followed the well-established pattern of tobacco industry-funded researchers trying to create controversy about research inconsistent with industry interests, the fact that Rodu had understated his financial ties to the industry, and, of course, showing how their criticism was based on statistical error that they made.
Addiction rejected our response because we would not delete the first two points and limit our response only to the statistical issue.
This blog post includes the response that Addiction rejected so that readers of Plurphanswat and Rodu’s critique do not think we did not have a response. We also include a summary of our interactions with the journal and the related email correspondence.
THE REJECTED RESPONSE
Consider the Source
“Harm reduction” is a key part of the tobacco industry’s strategy to avoid meaningful regulation and protect its political agenda and markets.[1] This agenda is premised on the existence of “hard core” smokers who “cannot or will not” quit.[2-4] Our paper, “The smoking population in the USA and EU is softening not hardening”,[5] undermined this agenda because it showed that, contrary to the hardening hypothesis, as smoking prevalence has declined over time, quit attempts increased in the USA and remained stable in Europe, US quit ratios increased (no data for EU), and consumption dropped in the USA and Europe.
There is a longstanding pattern of tobacco industry-funded experts writing letters criticizing work that threatens the industry’s position, first described in 1993 by then-JAMA Deputy Editor Drummond Rennie.[6] Rodu and various co-authors have written several such letters.[7-10] Another similarity to past efforts is industry-linked experts submitting critiques of a paper published in one journal to another,[11-15] which is also the case here, with this critique of our paper published in Tobacco Control being published in Addiction. One would have expected any criticism to have been published as a letter in Tobacco Control.
Addiction requires “full disclosure of potential conflicts of interest, including any fees, expenses, funding or other benefits received from any interested party or organisation connected with that party, whether or not connected with the letter or the article that is the subject of discussion.” As with another investigator supported by the tobacco industry,[16] the conflict of interest statement Plurphanswat and Rodu provide may not truly reflect the extent of Rodu’s involvement with the tobacco industry. For example:
• Rodu’s Endowed Chair in Tobacco Harm Reduction Research at the University of Louisville is funded by the U.S. Smokeless Tobacco Company (US Tobacco) and Swedish Match North America, Inc.[17]
• Rodu is a Senior Fellow at the Heartland Institute, which has received tobacco industry funding.[18-20]
• Rodu is a Member and Contributor to the R Street Institute, which has received tobacco industry funding.[19,21]
• Before moving to Louisville, Dr. Rodu was supported in part by an unrestricted gift from the United States Smokeless Tobacco Company to the Tobacco Research Fund of the University of Alabama at Birmingham.[8]
• Rodu was a keynote speaker at the 2013 Tobacco Plus Expo International, a tobacco industry trade fair to discuss “How has the tobacco retail business evolved; where was it fifteen years ago, where is it today and where is it going”.[22]
• Rodu has worked with RJ Reynolds executives between at least 2000 and 2009 to help promote industry positions on harm reduction, including specific products.[23-26]
The substance of Plurphanswat and Rodu’s criticism is that the statistically significant negative association between smoking prevalence and quit attempts and the positive association between prevalence and cigarettes smoked per day both become non-significant when more tobacco control variables are included in the model (state fixed effects, cigarette excise taxes, workplace smoking bans and home smoking bans). The problem with including all these variables is that it results in a seriously overspecified model, which splits any actual effects between so many variables that all the results become nonsignificant. The regression diagnostic for this multicollinearity is the Variance Inflation Factor (VIF); values of the VIF above 4 indicate serious multicollinearity. For the United States, adding all the other variables increases the VIF for the effect of changes in smoking prevalence from 1.8 in our model for quit attempts to 16.7, and from 1.8 in our model to 17.9 for cigarettes per day, respectively. Plurphanswat and Rodu’s model is a textbook case of why one has to be careful not to put too many variables in a multiple regression.
The Plurphanswat and Rodu criticism misrepresents our conclusions. We did not argue that drops in prevalence caused increased quit attempts and reduced consumption; we simply present the observation that, as prevalence falls, quit attempts increase and consumption fall or remain constant, which is the exact opposite of what the hardening hypothesis predicts.
The references and the full email correspondence with Addiction is available at http://tobacco.ucsf.edu/addiction-refuses-allow-discussion-industry-ties-criticism-our-“softening-paper”
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On 2015 Aug 12, Liam McKeever commented:
Dear Ms. Gluck,
Thank you for your comments. Training in the use of multiple databases was not the point of this paper. This paper was written in response to a recognition that many of the methods researchers use to perform their systematic reviews are not in fact systematic. A systematic review is meant to bring scientific methods into the process of writing a review. This means the methods of the review must be reproducible. Currently, many reviews that attempt to be truly systematic employ only the MEDLINE database because of its organized system of medical subject headings. If they do this correctly, they can perform an exhaustive search of the MEDLINE database. Our paper provided a technique for taking this systematic approach into an exhaustive search of both the MEDLINE and the PubMed databases, leading to a master formula, which could then be picked apart and improved upon by the scientific community. The techniques translate well to other databases and have recently been translated to EMBASE.
The argument that a complete systematic review should include an attempt to collect all relevant articles from multiple databases is well taken and commonly accepted. Preventing publication bias however is a much bigger picture than including multiple databases in a search strategy and was beyond the scope of this paper. To get all the null findings necessary to overcome publication bias would also mean including studies that either never entered or did not survive the peer review process. While such attempts should be made, a more achievable goal would be the thorough analysis of the publication bias present in a review where the search methodology is both explicit and reproducible.
The selection of appropriate databases for a systematic review, as you implied, varies greatly by profession. It was therefore also not in the scope of this paper. I do think there is some value in considering what it actually means than not all databases contain all journals. I find it highly unlikely that a bio-medically relevant journal would not be indexed in MEDLINE simply because they neglected to apply. It is much more likely that they applied and were rejected. Just as a systematic review has inclusion criteria at the level of the articles selected, databases have inclusion criteria at the level of the journals selected for cataloging. The degree of research quality and scope of topic areas are considered and determined to either meet or not meet the standards of the database. When we select a database for a systematic review, we are defining our inclusion criteria at the level of the journal. With this in mind, assuming adequate search methods were used and provided a thorough analysis of publication bias has been performed, one could make the argument that a properly selected major database pairing, like MEDLINE and PubMed may be acceptable for a systematic review. From a scientific methods perspective, we feel what is most important is that the inclusion criteria at all levels are explicit and that is what this paper attempts to facilitate.
Sincerely, Liam McKeever, MS, RDN
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On 2016 May 17, Annika Hoyer commented:
With great interest we noticed this paper by Nikoloulopoulos. The author proposes an approach for the meta-analysis of diagnostic accuracy studies modelling random effects while using copulas. In his work, he compares his model to the copula approach presented by Kuss et al. [1], referred to henceforth as KHS model. We appreciate a lot Nikoloulopoulos referring to our work, but we feel there are some open questions.
The author shows in the appendix that the association parameter from the copula is estimated with large biases from the KHS model, and this is what we also saw in our simulation study. However, the association parameter is not the parameter of main interest which are the overall sensitivities and specificities. They were estimated well in the KHS model, and we considered the copula parameter more as a nuisance parameter. This was also pointed out by Nikoloulopoulos in his paper. As a consequence, we are thus surprised that the bad performance in terms of the association parameter led the author to the verdict that the KHS method is 'inefficient' and 'flawed' and should no longer be used. We do not agree here, because our simulation as well as your theoretical results do clearly show that the KHS estimates the parameters of actual interest very well. Just aside, we saw compromised results for the association parameter also for the GLMM model in our simulation.
Nikoloulopoulos also wrote that the KHS approximation can only be used if the 'number of observations in the respective study group of healthy and diseased probands is the same for each study'. This claim is done at least 3 times in the article. But, unfortunately, there is no proof or reference or at least an example which supports this statement. Without a mathematical proof, we think there could be a misunderstanding in the model. In our model, we assume beta-binomial distributions for the true positives and the true negatives of the i-th study. They were linked using a copula. This happens on the individual study level because we wanted to account for different study sizes. For estimating the meta-analytic parameters of interest we assume that the shape and scale parameters of the beta-binomial distributions as well as the copula parameter are the same across studies, so that the expectation values of the marginal distributions can be treated as the meta-analytic sensitivities and specificities. Of course, it is true that we used equal sample sizes in our simulation [1], however, we see no theoretical reason why different sample sizes should not work. In a recently accepted follow up paper on trivariate copulas [2] we used differing sample sizes in the simulation and we also saw a superior performance of the KHS model as compared to the GLMM. In a follow-up paper of Nikoloulopoulos [3], he repeats this issue with equal group sizes, but, unfortunately, did not answer our question [4,5] with respect to that point.
As the main advantage of the KHS over the GLMM model we see its robustness. Our SAS NLMIXED code for the copula models converged better than PQL estimation (SAS PROC GLIMMIX) and much better that Gauss-Hermite-Quadrature estimation for the GLMM model (SAS PROC NLMIXED). This was true for the original bivariate KHS model, but also for the recent trivariate update. This is certainly to be expected because fitting the KHS model reduces essentially to the fit of a bivariate distribution, but without the complicated computations or approximations for the random effects as it is required for the GLMM and the model of Nikoloulopoulos given here. Numerical problems are also frequently observed if one uses the already existing methods for copula models with non-normal random effects from Liu and Yu [6]. It would be thus very interesting to learn how the authors’ model performs in terms of robustness.
Annika Hoyer, Oliver Kuss
References
[1] Kuss O, Hoyer A, Solms A. Meta-analysis for diagnostic accuracy studies: A new statistical model using beta-binomial distributions and bivariate copulas. Statistics in Medicine 2014; 33(1):17-30. DOI: 10.1002/sim.5909
[2] Hoyer A, Kuss O. Statistical methods for meta-analysis of diagnostic tests accounting for prevalence - A new model using trivariate copulas. Statistics in Medicine 2015; 34(11):1912-24. DOI: 10.1002/sim.6463
[3] Nikoloulopoulos AK. A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence. Statistical Methods in Medical Research 2015 11 Aug; Epub ahead of print
[4] Hoyer A, Kuss O. Comment on 'A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence' by Aristidis K Nikoloulopoulos. Statistical Methods in Medical Research 2016; 25(2):985-7. DOI: 10.1177/0962280216640628
[5] Nikoloulopoulos AK. Comment on 'A vine copula mixed effect model for trivariate meta-analysis of diagnostic test accuracy studies accounting for disease prevalence'. Statistical Methods in Medical Research 2016; 25(2):988-91. DOI: 10.1177/0962280216630190
[6] Liu L, Yu Z. A likelihood reformulation method in non-normal random effects models. Statistics in Medicine 2008; 27(16):3105-3124.
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On 2017 Feb 18, Clive Bates commented:
Erroneous interpretations have been placed on these results and overly confident conclusions drawn from very small numbers of imperfectly characterised teenagers. The headline recommendations were based on the behaviour of six out of 16 baseline e-cigarette users in a sample of 694 adolescents deemed not to be susceptible to smoking. Large conclusions drawn from small numbers should always be a cause for caution, as discussed in this article about this study by Five Thirty-Eight:
Ignore The Headlines: We Don’t Know If E-Cigs Lead Kids To Real Cigs by Christie Ashwandan, 11 September 2015
One should expect the inclination to use e-cigarettes to be caused by the same things that cause an inclination to smoke - they are similar habits (the former much less risky) and it is quite likely that those who used e-cigarettes first would have become smokers first in the absence of e-cigarettes - a concept known as shared liability. A range of independent factors that create a common propensity to smoke or vape, such as parental smoking, rebellious nature, delinquency etc. explain the association between vaping and smoking incidence but without this relationship being causal.
The authors try to address this by characterising teenagers non-susceptible to smoking if they answer “definitely no” when asked the following: “If one of your friends offered you a cigarette, would you try it?” and “Do you think you will smoke a cigarette sometime in the next year?”. The study concentrates on this group.
This is not a foolproof way of characterising susceptibility to smoking, which in any case is not a binary construct but a probability distribution. Nor is susceptibility a permanent condition for any young person - for example, if a teenage girl starts seeing a new boyfriend who smokes that will materially changes her susceptibility to smoking. The fact that some were deemed unsusceptible to smoking but were already e-cigarette users is grounds for further unease - these would be more likely to be the teens where the crude characterisation failed.
It is a near-universal feature of tobacco control research that the study presented is a wholly inadequate basis for any policy recommendation drawn in the conclusion, and this study is no exception:
These findings support regulations to limit sales and decrease the appeal of e-cigarettes to adolescents and young adults.
The findings do not support this recommendation, not least because the paper is concerned exclusively with the behaviour of young people deemed not susceptible to smoking and, within that group, a tiny fraction who progressed from vaping to smoking. Even for this group (6 of 16) the authors cannot be sure this isn't a result of mischaracterisation and that they would not have smoked in the absence of e-cigarettes. The approach to characterising non-susceptibility is far too crude and the numbers involved far too small to draw any policy-relevant conclusions.
But this isn't the main limitation. Much more troubling is that the authors made this policy recommendation without considering the transitions among young people who are susceptible to smoking - i.e. those more likely to smoke, and also those much more likely to use e-cigarettes as well as or instead of smoking. This group is much more likely to benefit from using e-cigarettes as an alternative to smoking initiation, to quit smoking or cut down or as a later transition as they approach adult life.
There are already findings (Friedman AS, 2015, Pesko MF, 2016, Pesko MF, Currie JM, 2016) that regulation of the type proposed by the authors designed to reduce access to e-cigarettes by young people has had unintended consequences in the form of increased smoking - something that should not be a surprise given these products are substitutes. While one may debate these findings, the current study makes no assessment of such effects and does not even cover the population that would be harmed by them. With these limitations, it cannot underpin its own over-confident and sweeping policy recommendation.
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On 2016 May 18, Chad Dube commented:
A researcher I highly respect once told me that a good review paper is one that engages and stimulates the reader to think critically and broadly about a particular phenomenon. In this sense I appreciate the commentary by Prof. Maniatis, which suggests the review at least succeeded in stimulating critical thought in at least one distinguished reader. And I will add that, though my initial reaction was that Prof. Maniatis' commentary is a polemic, it is clear that my critic takes the issues very seriously and raises some important research questions suggesting future experimental work. Nonetheless, the response, roughly a third of which seems to revolve around a passing reference to work by Koffka that has little to no bearing on the main points and conclusions of the review (and which misses the point of the reference to Koffka), contains a number of misintepretations of the points made in the review. I take responsibility for any lack of clarity that may have produced this.
I will detail a couple of examples that seem most directly related to the review (discussion of modeling methods, which don't fit algorithms as Prof. Maniatis stated but use algorithms to fit models, has to do with standard practice in the field itself and not the review).
Encoding and retrieval of statistical information about stimuli, such as the average diameter of circles in a set of circles with different diameters, may or may not involve direct "perception" of the average in the sense used by Prof. Maniatis. The relevant experiments, I suspect, have yet to be conducted. For this reason, "perceptual" may not be the best term and several different terms for the effects we have described are in in use (ensemble representation, statistical summary representation, etc). In my prior work (Dubé et al., 2014) I have discussed conceptual difficulties related to this term, and in my current work I favor "statistical summary representation" for this reason. However, the findings detailed in the review are indisputable. There is a clear consensus in the literature that participants can accurately recall the average. If they can accurately recall it, they must have encoded and stored it. There is no question as to whether such memories exist. I just returned from VSS at which there were around 50 presentations on the topic of summary statistical representation, according to one talk, and the special issue of JoV in which our review appeared was devoted entirely to summary statistical representation. Clearly a decent number of scientists remains convinced that the effects exist!
The final comment in the review, which Prof. Maniatis takes as our own admission that the existence of statistical representation is questionable, was meant to be somewhat tongue-in-cheek. How can the effects that have been attributed to remembered averages be due to memory for fine details of individual items when several studies, including the seminal one by Ariely (2001), demonstrate memory for the average despite chance performance on memory tests of the individual items from which the average was computed? It is in no way a statement that the effects don't exist (or even that we suspect they don't), even if taken at face value, and as I have detailed there is a quite large amount of empirical evidence to contradict the philosophical position of Prof. Maniatis. I will not detail all of these studies here, since a review detailing them already exists: Dubé and Sekuler (2015).
In my view, the conceptual nuances involved in discussion of summary statistical representation are suggestive of a need for more concrete, computational modeling, less verbal theorizing, and more neural data in this area.
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On 2015 Nov 17, Johan van Schalkwyk commented:
SPRINT strikes me as a work of pure genius. Conceive the following scenario: Take a carefully selected mixture of high-risk patients with a variety of blood pressures and risk factors, making sure that the low threshold for selection into the study is below the current sytolic blood pressure 'standard' of 140 mmHg. Apply two protocols, one that will aggressively reduce blood pressure in the intermediate term, another that's far more conservative. It's not beyond the bounds of possibility that a group of smart statisticians using current simulation methods and access to large hypertension databases might even predict the intermediate-term outcomes with a fair degree of confidence.
The fact that this trial is exactly what every manufacturer of anti-hypertensives needs at this point, that it was stopped very early, and that it seems to contradict the prior evidence that has informed treatment guidelines to date should make us pause and think. Particularly as the results from a highly selected group, treated for a few years, may well be extrapolated to lifetime treatment of many or even most people with a systolic blood pressure of over 130 mmHg. Let's see how this is marketed.
You may well choose to ignore the fact that one of the principal authors has received "personal fees" and/or grants from Bayer, Boeringer Ingelheim, GSK, Merck, AstraZeneca, Novartis, Arbor, Amgen, Medtronic and Forest. Your choice. Everyone has to make a living.
Of greater concern might be the near tripling of the rate of acute kidney injury or acute renal failure in the intensive-treatment group, as these conditions are not cheap to manage. We might also be a bit puzzled that almost half of the "extra deaths" in the standard therapy group were NOT from cardiovascular causes. How on earth does this work?
But anyone who understands a bit about MCMC methods should be in awe of the way this study was put together.
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On 2016 May 25, Lydia Maniatis commented:
When Todd et al say that understanding their demonstrations requires “a broader theoretical analysis of shape from shading that is more firmly grounded in ecological optics,” do they mean that there are things about the physics of how light interacts with surfaces that we don't understand? What kind of empirical investigations are they suggesting need to be performed? What kind of information do they think is missing, optically-speaking?
The fundamental issues are formal (having to do with form) not the details of optics and probabilities of illumination structure - as these authors have shown.
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On 2016 Apr 07, Lydia Maniatis commented:
Readers should read the last paragraphs of this article first. It indicates that the current results contradict the authors' previous results, and that they have no idea why that is. Nevertheless, they assume that one of the two must be right, and use a crude rule of thumb (the supposedly "simpler" explanation) to make their choice. I would take the third option.
"We see two possible explanations for the inconsistency between our previous work and that here:
The correct conclusions about the extent of contrast integration are drawn in our current work, with previous work being compromised by the loss of sensitivity with retinal eccentricity. For example, Baker and Meese (2011) built witch's hat compensation into their modeling, but not their stimuli (in which they manipulated carrier and modulator spatial frequencies, not diameter). A loss of experimental effect in the results (such as that in Figures 2a and 3a here) limits what the analysis can be expected to reveal. Indeed, Baker and Meese (2011) found it difficult to put a precise figure on the range of contrast integration, and aspects of their analysis hinted at a range of >20 cycles for two of their three observers. Baker and Meese (2014) made no allowance for eccentricity effects in their reverse correlation study. The contrast jitter applied to their target elements ensured they were above threshold, and so the effects of contrast constancy should come into play (Georgeson, 1991); however, we cannot rule out the possibilities that either (a) the contrast constancy process was incomplete or (b) internal noise effects not evident at detection threshold (e.g., signal dependent noise) compromised the conclusions.
The correct conclusions about the extent of contrast integration come from our previous work. Our current work points to lawful fourth-root summation, but not necessarily signal integration across the full range. On this account, signal integration takes place up to a diameter of about 12 cycles and a different fourth-root summation processes take place beyond that point. For example, from our results here we cannot rule out the following possibility: Beyond an eccentricity of ∼1.5° the transducer becomes linear and overall sensitivity improves by probability summation (Tyler & Chen, 2000), but uncertainty (Pelli, 1985; Meese & Summers, 2012) for more peripheral targets causes the slope of the psychometric function to remain steeper than β = 1.3 (May & Solomon, 2013).
We think Occam's razor would favor the first account over the second."
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On 2015 Nov 20, David Keller commented:
Why the blinding of experimental subjects should be tracked during a study, from start to finish
I wish to address the points raised by Folmer and Theodoroff in their reply [1] to my letter to the editor of JAMA Otolaryngology [2] concerning issues they encountered with unblinding of subjects in their trial of therapeutic MRI for tinnitus. These points are important to discuss, in order to help future investigators optimize the design of future studies of therapies for tinnitus, which are highly subject to the placebo, nocebo, Pygmalion and other expectation effects.
First, Folmer and Theodoroff object to my suggestion of asking the experimental subjects after each and every therapy session whether they think they have received active or sham placebo therapy in the trial so far (the "blinding question"). They quote an editorial by Park et al [3] which states that such frequent repetition of the blinding question might increase "non-compliance and dropout" by subjects. Park's statement is made without any supportive data, and appears to be based on pure conjecture, as is his recommendation that subjects be asked the blinding question only at the end of a clinical trial. I offer the following equally plausible conjecture: if you ask a subject the blinding question after each session, it will soon become a familiar part of the experimental routine, and will have no more effect on the subject's behavior than did his informed consent to be randomized to active treatment or placebo in the first place. Moreover, the experimenters will obtain valuable information about the evolution of the subjects' state of mind as the study progresses. We have no such data for the present study, which impairs our ability to interpret the subjects' answers to the blinding question, when it is asked only once at the end of the study.
Second, Folmer and Theodoroff state that I "misinterpreted" their explanation of why so many of their subjects guessed they had received placebo, even if they had experienced "significant improvement" in their tinnitus score. They object to my characterization of this phenomenon as due to the "smallness of the therapeutic benefit" of their intervention, but my wording summarizes their lengthier explanation, that their subjects had a prior expectation of much greater benefit, so subjects incorrectly guessed they had been randomized to sham therapy even if they exhibited a small but significant benefit from the active treatment. In other words, the "benefit" these subjects experienced was imperceptible to them, truly a distinction without a difference.
A therapeutic trial hopes for the opposite form of unblinding of subjects, which is when the treatment is so dramatically effective that the subjects who were randomized to active therapy are able to answer the blinding question with 100% accuracy.
Folmer and Theodoroff state that, in their experience, even if subjects with tinnitus "improve in several ways" due to treatment, some will still be disappointed if their tinnitus is not cured. Do these subjects then answer the blinding question by guessing they received placebo because their benefit was disappointing to them, imperceptible to them, as revenge against the trial itself, or for some other reason? Regardless, if you want to know how well they were blinded, independent of treatment effects and of treatment expectation effects, then you must ask them early in the trial, before treatment expectations have time to take hold. Ask the blinding question early and often. Clinical trials should not be afraid to collect data. Data are good; more data are better.
References:
1: Folmer RL, Theodoroff SM. Assessment of Blinding in a Tinnitus Treatment Trial-Reply. JAMA Otolaryngol Head Neck Surg. 2015 Nov 1;141(11):1031-1032. doi: 10.1001/jamaoto.2015.2422. PubMed PMID: 26583514.
2: Keller DL. Assessment of Blinding in a Tinnitus Treatment Trial. JAMA Otolaryngol Head Neck Surg. 2015 Nov 1;141(11):1031. doi: 10.1001/jamaoto.2015.2425. PubMed PMID: 26583513.
3: Park J, Bang H, Cañette I. Blinding in clinical trials, time to do it better. Complement Ther Med. 2008 Jun;16(3):121-3. doi: 10.1016/j.ctim.2008.05.001. Epub 2008 May 29. PubMed PMID: 18534323.
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On 2015 Dec 10, Lydia Maniatis commented:
This seems rather an odd choice of theme for a "Research Topic" in that it inspired a collection of papers with no conceptual coherence, out of many others that could have been selected on the basis of a common technique. It is somewhat like saying we'll put together an issue of physics papers that all used spectrometers. It's not really a "topic" unless you're specifically focussing on, e.g., pros and cons of the method.
The editors summary expresses the situation well: "In sum, this Research Topic issue shows several ways to use diverse kinds of noise to probe visual processing." As discussed in their exposition, noise has been historically used in multifarious ways for multifarious purposes.
I think the emphasis on technique rather than on theoretical problems is symptomatic of the conceptual impoverishment of the field. The use of the term "probe" has become common in this field, at least, indicating that a study is an exercise in a-theoretical data collection, rather than a methodic attempt to answer a question.
I would also add that noise as a technique to probe normal perception in normal conditions should be employed with caution, since it does not characterise normal scenes, but rather places unusual stress on the system which may respond in unusual ways.
Predictably, the results of the articles described seem undigested and of unclear value: E.g. "Hall et al. (2014) find that adding white noise increased the center spatial frequency of the letter-identification channel for large but not small letters;" (so...? how large is large...?) "Gold (2014) use pixel noise to investigate the visual information used by the observer during a size-contrast illusion. By correlating the observers頣lassification decision with each pixel of the noise stimuli, they find that the spatial region used to estimate the size of the target is influenced by the size of surrounding irrelevant elements" (or your theoretical definition of "irrelevant" needs adjustment).
If the goal of this issue was to show that you can make noise and get published, then it's a big success.
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On 2016 Jan 27, Lydia Maniatis commented:
A little way into their introduction, the authors of this article make the following clear and unequivocal assertion:
“These findings underscore the idea that the encoding of objects and shapes is accomplished by a hierarchical feedforward process along the ventral pathway (Cadieu et al., 2007; Serre, Kouh, Cadieu, Knoblich, & Krei- man, 2005; Serre, Oliva, & Poggio, 2007; Van Essen, Anderson, & Felleman, 1992). The question that arises is how local information detected in the early visual areas is integrated to encode more complex stimuli at subsequent stages.”
As all vision scientists are aware, the processes involved at every level of vision are both hierarchical and parallel, feedforward and feedback. These processes do not consist of summing “local information” to produce more complex percepts; a small local stimulus change can reconfigure the entire percept, even if the remaining “local information” is unchanged. This has been solidly established, on a perceptual and neural level, on the basis of experiment and logical argument, for many decades. (The authors' use of the term “complex stimuli,” rather than “complex percepts” is also misjudged, as all stimuli are simple in the sense that they stimulate individual, retinal photoreceptors in the same, simple way. Complexity arises as a result of processing - it is not a feature of the retinal (i.e. proximal) stimulus).
The inaccurate description of the visual process aligns with the authors' attempt to frame the problem of vision as a “summation” problem (using assumptions of signal detection theory), which, again, it decidedly is not. If the theoretical relevance of this study hinges on this inaccurate description, then it has no relevance. Even on its own terms, methodological problems render it without merit.
In order to apply their paradigm, the authors have constructed an unnatural task, highly challenging because of unnatural conditions - very brief exposures resulting in high levels of uncertainty by design, resulting in many errors, and employing unnaturally ambiguous stimuli. The task demands cut across detection, form perception, attention, and cognition (at the limit, where the subjects are instructed to guess, it is purely cognitive). (Such procedures may be common and old (“popular” according to the authors), but this on its own doesn't lend them theoretical merit).
On this basis, the investigators generate a dataset reflecting declining performance in the evermore difficult task. The prediction of their particular model seems to be generic: In terms of the type of models the authors are comparing, the probability of success appears to be 50/50; either a particular exponent (“beta”) in their psychometric function will decline, or it will be flat. (In a personal communication, one of the authors notes that no alternative model would predict a rising beta). The fitting is highly motivated and the criteria for success permissive. Half of the conditions produced non-significant results. Muscular and theory-neutral attempts to fit the data couldn't discover a value of “Q” to fit the model, so the authors “have chosen different values for each experiment,” ranging from 75 to 1,500. The data of one of five subjects were “extreme.” In addition, the results were “approximately half as strong as some previous reports, but “It ...remains somewhat of a mystery as to why the threshold versus signal area slopes found here are shallower than in previous studies, and why there is no difference in our study between the thresholds for Glass patterns and Gabor textures.” In other words, it is not known whether such results are replicable, and what mysterious forces are responsible for this lack of replicability.
It is not clear (to me) how a rough fit to a particular dataset, generated from an unnaturally challenging task implicating multiple, complex, methodologically/theoretically undifferentiated visual processes, of a model that makes such general, low-risk predictions (such as can be virtually assured by a-theoretical methodological choices) can elucidate questions of physiology or principle of the visual, or any, system.
Finally, although the authors state as their goal to decide whether their model “could be rejected as a model of signal integration in Glass pattern and Glass-pattern-like textures” (does this mean they think there are special mechanisms for such patterns?)” they do not claim to reject the only alternative that they compare (“linear summation”), only that “probability and not linear summation is the most likely basis for the detection of circular, orientation-defined textures.”
It is not clear what the “most likely” term means here. Most likely that their hypothesis about the visual system is true (what is the hypothesis)? Most likely to have fit their data better than the alternative? (If we take their analysis at face value, then this is 100% true). Is there a critical experiment that could allow us to reject one or the other? If no alternatives can be rejected, then what is the point of such exercises? If some can be, what would be the theoretical implications? Is there a value in simply knowing that a particular method can produce datasets that can be fit (more or less) to a particular algorithm?
The "summation" approach seen here is typical of an active and productive (in a manner of speaking) subdiscipline (e.g. Kingdom, F. A. A., Baldwin, A. S., & Schmidtmann, G. (2015). Modeling probability and additive summation for detection across multiple mecha- nisms under the assumptions of signal detection theory. Journal of Vision, 15(5):1, 1–16; Meese, T. S., & Summers, R. J. (2012). Theory and data for area summation of contrast with and without uncertainty: Evidence for a noisy energy model. Journal of Vision, 12(11):9, 1–28; Tyler, C. W., & Chen, C.-C. (2000). Signal detection theory in the 2AFC paradigm: Attention, channel uncertainty and probability summation. Vision Research, 40, 3121–3144.)
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On 2016 Jun 24, Lydia Maniatis commented:
The authors do two things in this study:
First, they point out that past studies on “constancy” have been hopelessly confounded due a. to condition-sensitivity of and ambiguity in what is actually percieved and b. questions that are confusing to observers because they are vague, ambiguous, unintelligible or unanswerable on the basis of the percept, thus forcing respondents to try to guess at the right answer. As a result, the designers of these studies have generated often incoherent data and proferred vague speculations as to the reasons for the randomness of the results.
Second, as though teaching (what to avoid) by example, they produce yet another study embodying all of the problems they describe. Using arbitrary sets of stimuli, they ask an arbitrary set of questions of varying clarity/answerability-on-the-basis-of-the-percept, and generate the typically heterogeneous, highly variable set of outcomes, accompanied by the usual vague and non-committal discussion. (The conditions and questions are arbitrary in the sense that we could easily produce a very different set of outcomes by (especially) changing the colors of the stimuli or (less importantly) changing the questions asked.) Thus, the only possible value of these experiments would be to show the condition-dependence of the outcomes. But this was an already established fact, and it is, furthermore, a fact that any experimenter in any field should be aware of. It's the reason that planning an experiment requires careful, theory-guided control of conditions.
The authors make no attempt to hide the fact that some of the questions they ask participants cannot be anwered by referring to the percept. For example,, they are asked about some physical characteristic of the simulus, which, of course, is inaccessible to either the human visual system and unavailable in the conscious percept. In these cases, we are not studying perception of the color of surfaces, but a different kind of problem-solving. The authors refer to answers “based on reasoning.” If we're interested in studying color perception, then the simple answer would be not to use this type of question. The authors seem to agree: “Although we believe that the question of how subjects can reason from their percepts is interesting in its own right, we think it is a different question from how objects appear. Our view is that instructional effects are telling us about the former, and that to get at the latter neutral instructions are the most likely to succeed...In summary, our results suggest that certain types of instructions cause subjects to employ strategies based on explicit reasoning— which are grounded in their perceptions and developed using the information provided in the instructions and training—to achieve the response they believe is requested by the experimenter.” This was all clearly known on the basis of prior experimence, as described in the introduction.
So, at any rate, the investigators express an interest in what is actually perceived by observers. But what is the question they're interested in answering? This is the real problem. The question, or goal, seems to be, “How do we measure color constancy?” But we don't measure things for measurement's sake. The natural follow-up is “Why do we want to measure color constancy?” What is the theoretical goal, or question we want to answer? This question matters because we can never, ever, arrive at some kind of universal, general, number for this phenomenon, which is totally condition-dependent. But I'm not able to discern, in these authors' work, any indication of their purpose in making these highly unreliable measurements.
Color constancy refers to the fact that sometimes, a surface “x” will continue to appear the same color even as the kind and intensity of the light it is projecting to the eye changes. On the other hand, it is equally possible for that same surface to appear to change color, even as the kind and intensity of the light it is reflecting to the eye remains the same. In both cases – constancy and inconstancy – the outcome depends on the total light projecting to the eye, and the way the visual system organizes it. In both cases – constancy and inconstancy – the visual principles mediating the outcome are the same.
The authors, in this and in previous studies, “measure constancy.” Sometimes it's higher, sometimes it's lower. It's condition-dependent. Even if they were actually measuring “constancy” in the sense of testing how an actually stable surface behaves under varying conditions, what would be the value of this data? We already know that constancy is condition-dependent, that it is often good or good enough, and that it can fail under certain well-understood conditions. (That these conditions are fairly well-understood is the reason the authors possess a graphics program for simulating “constancy” effects). How does simply measuring this rise and fall under random conditions (random because not guided by theory, meaning that the results won't help clarify any particular theoretical question) provide any useful information? What is, in short, the point?
Yet another twist in the plot is that in their experiments, the authors aren't actually measuring constancy. Because we are talking about simulations, in order to exhibit “constancy,” observes need (often) to actually judge two surface with different spectral characteristics as being the same. This criterion is based on assumptions made by the investigators as to what surfaces should look the same under different conditions/spectral properties. But this doesn't make sense. What does it mean, for example, if an observer returns “low constancy” results? It means that the conditions required for two actually spectrally different surfaces to appear the same simply didn't hold, in other words, that the investigators' assumptions as to the conditions that should produce this “constancy” result didn't hold. If the different stimuli were designed to actually test original assumptions about the specific conditions that do or do not produce constancy, fine. But this is not the case. The stimuli are simply and crudely labelled “simplified” and “more realistic.” This means nothing with respect to constancy-inducing conditions. Both of these kinds of stimuli can produce any degree of “constancy” or “inconstancy” you want.
In short, we know that color perception is condition-sensitive, and that some questions may fail to tap percepts; illustrating this this yet again is the most that this experiment can be said to have accomplished.
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On 2016 Feb 04, Ivan Shatsky commented:
It is a fruitful idea to use a high- throughput assay to fish out sequences that regulate translation initiation. I like this idea. It may result in very useful information provided that the experimental protocol is correctly designed to reach the goal of a study. However, while reading the text of the article I had an impression that the authors did not make a clear difference between the terms “IRES-driven translation” and “cap-independent” translation. In fact, cap-independent mechanisms may be of two kinds: a mechanism that absolutely requires the free 5’ end of mRNA (see e.g. Terenin et al. 2013. Nucleic Acids Res. 41(3):1807-16 and references therein and Meyer et al. 2015. Cell 163(4): 999-1010 ) and that which is based on internal initiation. Only in the latter case a 5’ UTR starts penetrating the mRNA binding channel of ribosomes with an internal segment of the mRNA rather than with a free 5’ end. Consequently, the experimental design should be distinct for these two modes of cap-independent translation. The method of bicistronic constructs used by the authors is suitable exclusively to identify IRES-elements. However, this approach is sufficiently reliable when it is employed in the format of bicistronic RNAs transfected into cultured cells. It is repeatedly shown that the initial format of bicistronic DNAs is extremely prone to almost unavoidable artifacts (for literature, see ref. 48 in the paper and the review by Jackson, R.J. The current status of vertebrate cellular mRNA IRESs. Cold Spring Harb Perspect Biol, 2013; 5). The control tests to reveal these artifacts which are still used (unfortunately!) by many researchers are not sensitive enough to detect formation of few percents of monocistronic mRNAs. (To this end, one should perform precise and laborious experiments which are not realistic in the case of high-throughput assays.). The capping of these aberrant mono- mRNAs can produce a dramatic stimulation of their translation activity (20-100 fold, depending on cell line). Therefore, even few percents of capped mono-mRNAs may result in a high activity of the reporter as compared to an almost zero activity of empty vector (see Andreev et al. 2009. Nucleic Acids Res.37(18):6135-47 and references therein). Real-time PCR assessment of mRNA integrity (Fig. S4) is an easy way to miss these few percents of aberrant transcripts. The other concern is genome-wide cDNA/gDNA estimation. The ratio for e.g. “c-myc IRES” is 2<sup>-1.6</sup> which is roughly 1/3 (Fig. S3). Does this mean that 2/3 of c-myc transcripts are monocistronic rather than bicistronic? I had a general impression that the authors were not aware of serious pitfalls inherent to the method of bicistronic DNA constructs and simply adapted this method to their high throughput assay. At least, I did not find citations of papers that discussed this important point.
The data in section Supplementary materials (Figs. S5 and S6) give us expressive and compelling evidence of such kind of artifacts: indeed, some 174 nt long fragments from the EMCV IRES possessed an IRES activity. Moreover, one of them with GNRA motif had the activity similar to that for the whole EMCV IRES (!?). This result is in an absolute contradiction with our current knowledge on this picornaviral IRES, one the best studied IRES elements! Parts of the EMCV IRES are known to have no activity at all! Thus, the most plausible explanation is that the EMCV fragments harbor cryptic splice sites. The same is true for other picornavirus IRESs examined in these assays. The HCV IRES tested by the authors in the same experiments worked only as a whole structure (Fig.S6B), in a full agreement with data of literature. However, this result may not encourage us as it just means that the data obtained in this study may be a mixture of true regulatory sequences with artifacts. We should keep in mind that the existence of viral IRES-elements is a firmly established fact. They have a complex and highly specific organization with well defined boundaries and THEY ARE ONLY ACTIVE AS INTEGRAL STRUCTURES. The minimal size of IRESs from RNAs of animal viruses is >300 nts. Their shortening inactivates them and therefore, they cannot be studied with cDNA fragments of 200 nt long or less. Thus, I think it was a mistake to mix viral IRESs with cellular mRNA sequences. As to cellular IRESs, none of them has been characterized and hence we do not know what they are and whether they even exist. For none of them has been shown that they do not need a free 5’ end of mRNA to locate the initiation codon. Some of them have already been disproved (c-Myc, eIF4G, Apaf-1 etc.). By the way, I do not know any commercial vector that employs a cellular IRES. Thus, I think that we should first find adequate tools to identify cellular IRESs, characterize several of them, and only afterwards we may proceed to transcriptome-wide searching for cellular IRESs.
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On 2016 Mar 20, Linda Z Holland commented:
In my review, I did not intend to criticize the ability of ascidian development to say something about the role of gene subnetworks in developing systems in vivo—it is a fruitful approach worthy of vigorous pursuit. Ascidians are highly tractable for experimental embryology and have scaled-down genomes and morphologies (at least with respect to vertebrates). As a result, noteworthy progress is being made in elucidating the gene networks involved in ascidian notochord development (José-Edwards et al. 2013, Development 140: 2422-2433) and heart development (Kaplan et al. (2015. Cur Opin Gen Dev 32: 119-128). It is currently a useful working hypothesis to make close comparisons between gene subnetworks in ascidians and other animals (Ferrier 2011. BMC Biol 9: 3). At present, however, the genotype-to-phenotype relationship is an unsolved problem in the context of a single species, and to consider the problem across major groups of animals is to venture deep into terra incognita. Much more work on the development in the broadest range of major animal taxa will be required to determine how (or even if) genotypes can predict phenotypes in vivo in embryos and later life stages. Studies of this complex subject, which are likely to require a combination of experimental data and computational biology (Karr et al, 2012. Cell 150: 389-401) are still in their infancy. That said, when I consider the developmental biology of animals in general, I think it is very likely that the highly determinate embryogenesis and genomic simplifications of ascidians are evolutionarily derived states. It is possible that this ancestor may have been more vertebrate-like than tunicate-like. For example, it might have had definitive neural crest, and the situation in modern ascidian larvae, which apparently have part of the gene network for migratory neural crest, may represent a simplification from a more complex ancestor. In the absence of fossils that could represent the common ancestor of tunicates and vertebrates, we cannot reconstruct a reasonable facsimile of this ancestor. Given that tunicates are probably derived, it is not very likely that any amount of research on modern chordates will solve this problem.
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On 2016 May 17, Duke RNA Biology Journal Club commented:
These comments were generated from a journal club discussion:
We were excited to read and discuss this paper as many of us have questions pertaining to mRNA localization. This technique theoretically allows for imaging of mRNAs without genetic manipulation meaning mRNAs at native expression levels can be tracked in live cells. However, as with many cutting-edge papers, more work is needed before this will become commonplace in the lab.
Most current methods to track mRNAs in live cells involve aptamer based methods which require genetic manipulation of mRNA PMCID: PMC2902723. Additionally, the most commonly used aptamer system, the MS2-MCP system, has become controversial in light of recent findings that the MS2 coat protein stabilizes the aptamer bearing constructs Garcia JF, 2015. In this paper, Fig 1F and 1G replicated these findings and also reassured us that the RCas9 technique would not have the same downfall. While this is certainly a good thing, we were unconvinced this technique was better than FISH (Fig 2), other than having the potential for live cell imaging.
Unfortunately, we found the live cell imaging, which was limited to Fig 3B, to be disappointing. First, we observed that unless an mRNA is strictly localized, as in stress granules, live imaging shows a diffuse mass within the cytosol. Second, imaging was performed with ACTB mRNA which is highly abundant. We don’t think live cell imaging would work as well for low abundance mRNAs due to high background signal. Finally, while specialized imaging software can detect the pile-ups of mRNA in localized foci, we are concerned that tracking individual mRNA may prove a hurdle. Cell models for mRNA localization are large cells such as fibroblasts and neurons, we would be interested to see the ability of this system within these cell types.
One major flaw with this system is the lack of ability to monitor nuclear localized RNA such as lncRNA or splicing machinery. Since since the RCas9 and sgRNA have to first be produced in the nucleus, the majority of the signal in all the figures came from the nucleus. There is a split-GFP-PUM-HD system that has been used to successfully track mRNA in mitochondria Ozawa T, 2007. Perhaps a similar concept could be used with the Cas9 system. This would prove an advantage to the Pumilio system since only the sgRNA needs to be modified instead of the entire protein.
Overall, this is a great start towards a new, tagless, method of mRNA tracking. We look forward to future developments and improvements of this exciting technique.
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On 2016 Jun 21, Evelina Tutucci commented:
We have also recently discussed Nelles et al. Nelles DA, 2016. Since we are interested in developing new techniques for studying gene expression and mRNA localization at the single molecule level, a potential tag-less system to detect mRNAs in fixed and live cells would be a further advance. As pointed out by the Duke RNA Biology journal club we think that Nelles et al. represents an attempt to apply the Cas9 System to detect endogenous mRNA molecules. Unfortunately, no evidence is presented to demonstrate that this system is ready to be used to study gene expression at the single molecule level, as the MS2-MCP system allows. The RNA letter by Garcia and Parker Garcia JF, 2015 showed that in S. cerevisiae the binding of the MS2 coat protein to the MS2-loops diminished tagged mRNA degradation by the cytoplasmic exonuclease Xrn1. However, these observations were not extended to higher eukaryotes. Previous work from our lab described the generation of the beta-actin-MS2 mouse, whereby all the endogenous beta-actin mRNAs were tagged with 24 MS2 loops in the 3’UTR (Lionnet T, 2011, Park HY, 2014). This mouse is viable and no phenotypic defects are observed. In addition, control experiments were performed to show that the co-expression of the MS2 coat protein in the beta-actin-MS2 mouse allowed correct mRNA degradation and expression (Supplementary figure 1b, Lionnet T. et al 2011). Furthermore, multi-color FISH (Supplementary figure 6, Lionnet T. et al 2011) showed substantial co-localization between the ORF FISH probes and MS2 FISH probes, demonstrating the validity of this model. We think that the observations by Garcia and Parker are restricted to yeast because of the short half-life of their mRNAs, wherein the degradation of the MS2 becomes rate-limiting. Based on our extensive use of the MS2-MCP system, we think that higher eukaryotes may have more time to degrade the high affinity complexes formed between MS2-MCP, providing validation for this system to study multiple aspects of gene expression. In conclusion, we think that the MS2-MCP system remains to date the best method to follow mRNAs at the single molecule level in living cells. For the use of the MS2-MCP system in S. cerevisiae we have taken the necessary steps to improve it for the study of rapidly degrading mRNAs and are preparing this work for publication.<br> Evelina Tutucci and Maria Vera, Singerlab
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On 2017 Jul 03, P Jesper Sjöström commented:
Thanks for your interest in our work. I would like to make the following points:
We did not actually say 'no connections in mature cortex' -- that quote is certainly not lifted from Mizusaki et al Nat Neurosci 2016. We said "In fact, it was recently reported that, surprisingly, pyramidal cells in visual cortex of mature animals do not seem to interconnect at all, neither bidirectionally nor unidirectionally12," where 12 refers to Jiang et al. We thus say that Jiang et al report that PCs do not seem to interconnect, we do not say that there are no PC-PC connections in mature cortex. What Jiang et al state and what our opinion about that statement is, those are different things.
The intention of that passage in Mizusaki et al is to point out that Brunel is using my data from Song et al as a gold standard, but this may or may not be appropriate, since my connectivity data was acquired from a developmental snapshot in time (just after eye opening, typically postnatal day 14-16), whereas Brunel is in fact focussing on the functioning of the mature brain, when circuits are wired up. Our intention was thus to acknowledge that my own data need not be the ground truth, and this has important implications for the validity of the Brunel study. The Tolias study provides an alternative view: "the most compelling and consistent difference across experiments is the age of the animals tested, suggesting that mature cortical circuits are not identical to developing circuits." Such a developmental difference would important in the context of the Brunel study. Again, this is not necessarily my opinion, but as scientists, we have to acknowledge this possibility.
In the Tolias study, they report in Fig S14 that they found precisely zero L5 PC-PC connections even after 150 attempts, which is in stark contrast to my connectivity data presented in Song et al. Indeed, if you do a Chi-squared test for 931/8050 versus 0/150, you will find that this is a highly significant difference. We can debate the accuracy of the Tolias measurement (like they do in Barth et al Science 2016 353:1108, as you point out), but if we do so, we should also debate the accuracy of my measurements in juveniles, as presented in Song et al. While it is true that my data in Song et al is more in line with e.g. Thomson et al Cereb Cortex 2002 than with Jiang et al, the key point in the context of Brunel's theoretical study is that the ground truth is not necessarily well established.
In summary, I certainly believe in my own connectivity data set, and I think Brunel's study provides a very compelling theoretical framework for explaining such connectivity patterns, but I feel obliged to point out a few possible caveats associated with my connectivity data set. Jiang et al provide one such key caveat. I hope this clarifies somewhat.
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On 2016 Jun 24, Ole Jakob Storebø commented:
We think that the clinicians prescribing methylphenidate for ADHD and others have been insufficiently critical of the literature for decades, trusting that the quality of methylphenidate research was reasonable. In accordance, Shaw in an editorial accompanying our JAMA article Storebø OJ, 2016 stated that the Epstein et al. review on methylphenidate for adults with ADHD was an example of good assessments of quality Shaw P, 2016. It seems Shaw erred, as the Epstein et al. review has now been withdrawn from The Cochrane Library due methodological flaws Epstein T, 2016.
Banaschewski et al. suggest that we included five trials in our analyses that should have been excluded. We think they are wrong. They highlight four trials which they cite as having used “active controls” whereas these are actually co-interventions, used in both the methylphenidate and the control group. Such trials are includable in accordance with our protocol Storebø OJ, 2015. Moreover, excluding these trials from our review would only have produced negligible changes in our results. Furthermore, the trial including children aged 3 to 6 years ought also to have be included in accordance with our protocol. Excluding all five trials would not have changed our conclusions at all. We concluded that methylphenidate might improve teacher reported symptoms of ADHD. However, the very low quality of the evidence, the magnitude of that effect size is uncertain. A change in the effect size of 0.12 points on the standardised mean difference of this outcome would not change anything.
In a subgroup analysis comparing parallel trials and crossover trials, we did not find a significant difference either. However, we noted considerable heterogeneity between the two groups of trials. It is not recommended to pool cross-over trials which only have “end-of-trial data” with parallel group trials (http://handbook.cochrane.org/) and had we done so we would have would risked introducing a “unit-of-analysis error” as we only had “end-of-trial data” from these cross-over trials.
We agree that the variability of the minimal relevant difference is important which is why we reported the 95% confidence interval of the transformed mean value in our review Storebø OJ, 2015. Banaschewski et al. also suggest that we have overlooked information in the Coghill 2007 trial and thereby wrongly assessed this as a trial with “high risk of bias”. We stated in our protocol that we would consider trials with one or more unclear or high risk of bias domain as trials with high risk of bias Storebø OJ, 2015.
We did not overlook information from the Coghill 2007 trial but twice emailed the authors for additional information. They did not respond. The information required is not available in the published study. We presented the risk of bias assessments for the various domains of all 185 included trials. It is correct that we assessed seven cross-over trials as low risk of bias and not six as reported. Thank you for spotting this error. The seventh trial is reported, however, in our table in which the risk of bias assessments for all the domains is shown. All trials, irrespective of vested interest bias, were regarded as having a high risk of bias due to broken outcome assessor blinding given the easily recognisable, well-known adverse effects of methylphenidate. When adding this seventh cross-over trial to the subgroup analysis on the outcome “teacher-rated ADHD symptoms – cross-over trials”, we now find significant differences between the trials with “high” compared to “low” risk of bias (standardised mean difference (SMD) -0.96 [95% confidence interval -1.09 to -0.82] compared to -0.64 [-0.91 to -0.38]. Test for subgroup difference: Chi² = 4.27, df = 1 (P = 0.04), I² = 76.6%).
Banaschewski et al. focus only on our assessment of risk of bias and do not mention the core instrument for assessing quality of meta-analyses namely the Grades of Recommendation Assessment Development and Evaluation (GRADE) approach Andrews J, 2013. Our assessment of the evidence as “very low quality” is not only based on the assessment of risk of bias, but also on other factors such as heterogeneity, imprecision, and indirectness of the evidence. This is clearly reported in our review.
We downgraded the quality of the included trials in the meta-analysis for imprecision and for moderate heterogeneity. The durations of included trials were short, with an average of 75 days. Most patients receive methylphenidate treatment for substantially longer periods and the beneficial effects may diminish over time Jensen PS, 2007 Molina BS, 2009. The short trial duration could suggest the need for further downgrading for “indirectness” according to GRADE Andrews J, 2013. We did not downgrade for this, but we could have. This further underlines that the evidence for the benefits and harms for the use of methylphenidate for children and adolescents with ADHD is of very low quality.
We have assessed 71 trials as having high risk of bias in the “vested interest” domain as they were funded by the industry and/or the authors were affiliated with the industry.
It is not incorrect for us to state that none of the trials funded by the pharmaceutical industry showed a low risk of bias in all other areas as we considered all the trials as high risk of bias on the domain of blinding. This is clearly reported in our review.
We have now conducted the requested subgroup analysis comparing those trials with high compared to low risk of vested interest bias on the teacher-rated ADHD symptoms outcome. The effect of methylphenidate in the 14 trials with high risk of vested interest bias was SMD -0.86 [-0.99 to -0.72] compared to SMD -0.50 [-0.69 to -0.31] in the 5 trials with low risk of vested interest bias. Test for subgroup differences is Chi² = 8.67, df = 1, P = 0.003. So even in this small sample we find a significant difference.
We recommend Banaschewski et al. to read the essay by John P Ioannidis about vested interests Ioannidis JP, 2016.
It is important to stress that the results of our review would have been the same had we disregarded the issue of vested interest.
Had there been inconsistencies regarding one domain of bias in a few trials they would not change the fact that these trials are to be considered as trials at high risk of bias. For example, in two trials, Konrad 2004 and Konrad 2005, there is inconsistency in how our author teams assessed the randomisation process. However, both trials have several other domains at “unclear risk of bias” or “high risk of bias”. In the Ullman 2006 trial, three domains are assessed as “unclear risk of bias”. In Wallace 1994, five domains are assessed as being of “unclear risk of bias” and one as “high risk of bias”. In Wallander 1987, five domains are assessed as “unclear risk of bias”. Even if there was inconsistency between one or two items, these trials are high risk of bias trials. There may well be small differences in our judgements, but that does not change the fact that the trials included are, in general, trials at high risks of bias Storebø OJ, 2015. It is important to understand that we followed the Cochrane guidelines in every aspect of our review.
Conclusions
We have demonstrated that the trial selection in our review was not flawed and was undertaken with sufficient scientific justification The effect sizes are not too small. We have followed a sound methodology for assessing risk of bias and our conclusion is not misleading. We are concerned about the state of the academic literature and at the financial and academic waste that has occurred, given that more than 250 reviews and 3000 single works have been published on psychostimulants for ADHD treatment. Despite this, there is still no sound evidence regarding the benefits and harms of methylphenidate.
Ole Jakob Storebø, Morris Zwi, and Christian Gluud.
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On 2017 May 24, Jordan Anaya commented:
I think readers of this article will be interested in a comment I posted at F1000Research, which reads:
I would like to clarify and/or raise some issues with this article and accompanying comments.
One: Reviewers Prachee Avasthi and Cynthia Wolberger both emphasized the importance of being able to sort by date, and in response the article was edited to say: "Currently, the search.bioPreprint default search results are ordered by relevance without any option to re-sort by date. The authors are aware of the pressing need for this added feature and if possible will incorporate it into the next version of the search tool."
However, it has been nearly a year and this feature has not been added.
Two: The article states: "Until the creation of search.bioPreprint there has been no simple and efficient way to identify biomedical research published in a preprint format..."
This is simply not true as Google Scholar indexes preprints. This was pointed out by Prachee Avasthi and in response the authors edited the text to include an incorrect method for finding preprints with Google Scholar. In a previous comment I pointed out how to correctly search for preprints with Google Scholar, and it appears the authors read the comment given they utilize the method at this page on their site: http://www.hsls.pitt.edu/gspreprints
Three: In his comment the author states: "We want to stress that the 'Sort by date' feature offered by Google Scholar (GS) is abysmal. It drastically drops the number of retrieved articles compared to the default search results."
This feature of Google Scholar is indeed limited, as it restricts the results to articles which were published in the past year. However, if the goal is to find recent preprints then this limitation shouldn't be a problem and I don't know that I would classify the feature as "abysmal".
Four: The article states: "As new preprint servers are introduced, search.bioPreprint will incorporate them and continue to provide a simple solution for finding preprint articles."
New preprint servers have been introduced, such as preprints.org and Wellcome Open Research, but search.biopreprint has not incorporated them.
Five: Prachee Avasthi pointed out that the search.biopreprint search engine cannot find this F1000Research article about search.biopreprint. It only finds the bioRxiv version. In response the author stated: "The Health Sciences Library System’s quality check team has investigated this issue and is working on a solution. We anticipate a quick fix of this problem."
This problem has not been fixed.
Competing Interests: I made and operate http://www.prepubmed.org/, which is another tool for searching for preprints.
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On 2016 Sep 16, John Ioannidis commented:
Dear Hilda,
thank you for the very nice and insightful commentary on my article. I think that my statement "Currently, probably more systematic reviews of trials than new randomized trials are published annually" is probably correct. The quote of 8,000 systematic reviews in the Page et al. 2016 article is using very conservative criteria for systematic reviews and there are many more systematic reviews and meta-analyses, e.g. there is a factory of meta-analyses (even meta-analyses of individual level data) done by the industry combining data of several trials but with no explicit mention of systematic literature search. While many papers may fail to satisfy stringent criteria of being systematic in their searches or other methods, they still carry the title of "systematic reviews" and most readers other than a few methodologists trust them as such. Moreover, the 8,000 quote was from February 2014, i.e. over 2.5 years ago, and systematic reviews' and meta-analyses' publication rates rise geometrically. Conversely, there is no such major increase in the annual rate of published randomized controlled trials. Furthermore, the quote of 38,000 trials in the Cochrane database is misleading, because it includes both randomized and non-randomized trials and the latter may be the majority. Moreover, each randomized controlled trial may have anywhere up to hundreds of secondary publications. On average within less than 5 years of a randomized trial publication, there are 2.5 other secondary publications from the same trial (Ebrahim et al. 2016). Thus the number of published new randomized trials per year is likely to be smaller than the number of published systematic reviews and meta-analyses of randomized trials. Actually, if we also consider the fact that the large majority of randomized trials are small/very small and have little or no impact, while most systematic reviews are routinely surrounded by the awe of the "highest level of evidence", one might even say that the number of systematic reviews of trials published in 2016 is likely to be several times larger than the number of sizable randomized trials published in the same time frame.
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On 2017 Feb 06, GARRET STUBER commented:
*This review was completed as part of a graduate level circuits and behavior course at UNC-Chapel Hill. The critique was written by students in the class and edited by the instructor, Garret Stuber.
Comments and critique
Written by Li et al., this paper investigated a class of oxytocin receptor interneurons (OxtrINs) on which the same group first characterized in 2014 [1]. OxtrINs are a subset of somatostatin positive interneurons in the medial prefrontal cortex (mPFC) that seem to be important for sociosexual behaviors in females, specifically during estrus and not diestrus. To complement their previous story, here the authors concluded that OxtrINs in males regulate anxiety-related behaviors through the release of corticotropin releasing hormone binding protein (Crhbp). While we agree that these neurons could be mediating sexually dimorphic behaviors, it is unclear how robust these differences really are.
We had some technical issues with this paper. First, it is unclear exactly how many mice were allotted to each experimental group, and it would have been useful to see individual data in each of the behavioral experiments, so that we can better understand some of the variability in the authors’ graphs. Even among different experiments, there were variable sizes of n (e.g. Fig. 5F-H, “n = 8-14 mice per group”). There was also no mention of how many cells per animal were tested for each brain slice experiment; instead, we received total numbers of cells tested per group. This paper did not include the complementary female data to Fig. 4F-G and Fig. 5A-B, the experiments pairing blue light with Crhr1 antagonist or Crhbp antagonist. We would have appreciated seeing this data adjacent to that for the males. In addition, there was no mentioned control for the optogenetic experiments. The authors only compared responses between light on and light off trials. Typically in optogenetic approaches, a set of control mice are also implanted with optic fibers and flashed with blue light in the absence of virus to test whether the light alone influences behavior. Incidentally, there is evidence that blue light influences blood flow, which may affect neuronal activity [2]. It was also unclear during the sociosexual behavioral testing whether the males were exposed to females in estrus or diestrus. In all, lack of detailed sample sizes and controls made it difficult to assess how prominent these sex differences were.
These issues aside, knocking out endogenous Oxtr in their targeted interneuron population was a key experiment, as it demonstrated that oxytocin signaling in OxtrINs is important in anxiety-related behaviors in males, but not in females regardless of the estrus stage. They did this using a floxed Oxtr mouse and deleted OxtR using a Cre-inducible virus, allowing for temporal and cell-type-specific control of this deletion, and subsequently measured the resulting phenotype using an elevated plus maze and open field task. The authors also validated that changes in exploration were not due to hyperactivity. We think these experiments are convincing.
TRAP profiling, which the same research group pioneered in 2014 [3], provided a set of genes enriched in OxtrINs. TRAP targets RNAs while they are translated into proteins, so we think their results here are particularly relevant. Moreover, the authors provided a list of genes enriched in sex-specific OxtrINs, a useful resource for those interested in gene expression differences in males and females. Once they identified Crhbp, an inhibitor of Crh, they hypothesized that OxtrINs were releasing Crhbp to modulate anxiogenic behaviors in males. The authors next measured Crh levels in the paraventricular nucleus of the hypothalamus and found that Crh levels are higher in females than males. They thus concluded Crh levels were driving sex differences associated with OxtrINs. We wonder whether Crh levels are also higher in the female mPFC, but we agree here too.
To demonstrate that Crhbp expressed by OxtrINs is important in modulating anxiety-like behaviors in males, the authors targeted Crhbp mRNA using Cre-inducible viral delivery of an shRNA construct and subsequently tested anxiety-related behaviors. They found that knocking down Crhbp was anxiogenic in males and not in females. This was a critical experiment, but the shRNA constructs targeting Crhbp were validated solely in a cell line. It would have been more appropriate to perform a western blot on mPFC punches of adult mice, showing whether this lentiviral construct knocked down Crhbp expression in the mouse brain prior to behavioral testing. In fact, it also would have been useful to see a quantification of the shRNA transfection rate, as well as its specificity in vivo. As stated above, we also do not know the distribution of behavioral responses here either. Without these pieces of information, it is difficult to assess how reliable or robust their knockdown was.
The authors concluded that sexually dimorphic hormones act through the otherwise sexually monomorphic OxtrINs to regulate anxiety-related behaviors in males and sociosexual behaviors in females. We agree that OxtrINs interact with oxytocin and Crh to bring about sex-specific phenotypes, but we also think that using additional paradigms testing anxiety and social behaviors, such as a predator odor, novelty-suppressed feeding or social grooming, could shed more light on the nuances of mPFC circuitry. In addition, the authors suggested that OxtrINs are sexually monomorphic because they are equally abundant in males and females. The authors’ TRAP data however suggested that OxtrINs of males and females have different gene expression profiles (Table S2), thus indicating that these interneurons may form different connections in each sex that mediate the electrophysiological and behavioral differences we see in this study.
It would be interesting to overexpress Crhbp in female mice, preferably in a cell-type-specific manner, to see whether female mice would demonstrate the anxiety-like behavior seen in males. If the Crh:Crhbp balance is in fact mediating this sexually dimorphic behavior through OxtrINs, we would expect that doing these manipulations may “masculinize” the females’ behavior. Regardless, we believe that this study opens opportunities for future work into how oxytocin and Crh release from the hypothalamus may act together to coordinate behavior. It will also be interesting to see if single-cell RNA sequencing could provide insight into whether OxtrINs can be further divided into sexually dimorphic subtypes. As the authors pointed out, understanding the dynamics of Crh and oxytocin in the mPFC will be important for gender-specific therapy and treatment.
[1] Nakajima, M. et al. Oxytocin modulates female sociosexual behavior through a specific class of prefrontal cortical interneurons. Cell. 159, 295-305 (2014).
[2] Rungta, R. L. et al. Light controls cerebral blood flow in naïve animals. Nature Communications. 8, 14191 (2017).
[3] Heiman, M. et al. Cell-type-specific mRNA purification by translating ribosome affinity purification (TRAP). Nature Protocols. 9, 1282-1291 (2014).
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On 2016 Oct 13, Giorgio Casari commented:
Increased or decreased calcium influx?
In this elegant paper the authors propose that loss of m-AAA (i.e. the depletion of both SPG7 and AFG3L2) facilitates the formation of active MCU complexes through the increased availability of EMRE, thus (i) increasing calcium influx into mitochondria, (ii) triggering MPTP opening and (iii) causing the consequent increase of neuronal cytoplasmic calcium leading to neurodegeneration. We previously reported that loss or reduction of AFG3L2 causes (i) decreased mitochondrial potential and fission, thus (ii) decreased calcium entry and (iii) the consequent augmented neuronal cytoplasmic calcium leading to neurodegeneration. While the functional link of m-AAA with MAIP and MCU-EMRE represents a new milestone in the characterization of the roles this multifaceted protease complex, we would like to comment on the conclusions pertaining to the calcium dynamics. 1. In SPG7/AFG3L2 knock-down HeLa cells (Figure S6A) mitochondrial matrix calcium is dramatically reduced (approx. from 100 to 50 microM) following histamine stimulation, which triggers IP3-mediated calcium release from ER. This reduction is in complete agreement with the one we previously detected in Afg3l2 ko MEFs (Maltecca et al., 2012), and that we also confirmed in Afg3l2 knock-out primary Purkinje neurons (the cells that are primarily affected in SCA28) upon challenge with KCl (Maltecca et al., 2015). The decreased mitochondrial calcium uptake correlates with the 40% reduction of mitochondrial membrane potential in SPG7/AFG3L2 knock-down cells (Figure S6B), as expected since the mitochondrial potential is the major component of the driving force for calcium uptake by MCU. Accordingly, these data are in line with the decreased mitochondrial membrane potential observed in Afg3l2 knock-out Purkinje neurons (Maltecca et al., 2015). We think that this aspect is central, because the respiratory defect is the primary event associated to m-AAA deficiency and neurodegeneration. So, the data of König et al. agree with our own findings that mitochondrial matrix calcium is reduced after m-AAA depletion. 2. By a different protocol (SERCA pumps inhibition and ER calcium leakage; Figure 6 C-F), the authors detected a small increase of mitochondrial calcium concentration in SPG7/AFG3L2 knock-down HeLa cells (from approx. 3 to 6 microM). The huge difference in calcium concentration detected in the two experiments (100 to 50 microM in Figure S6A and 3 to 6 microM in Figure 6 C) possibly reflects the stimulated (histamine) vs. unstimulated (calcium leakage) conditions, this latter being more difficult to correlate to physiologic neuronal situation. 3. The authors show increased sensitivity to MPTP opening in the absence of m-AAA and they propose the consequent calcium release as the cause of calcium deregulation and neuronal cell death. ROS are strong sensitizers of MPTP to calcium and thus favor its opening. It is well known that m-AAA loss massively increases intramitochondrial ROS production. Thus, higher ROS levels, rather than high calcium concentrations, can be the trigger of MPTP opening. Taking all this into consideration, we think that mitochondrial depolarization (as shown in Figure S6B) and decreased mitochondrial calcium entry (Fig S6A), even in the presence of increased amount of MCU-EMRE complexes, may lead to inefficient mitochondrial calcium buffering and, finally, to cytoplasmic calcium deregulation. ROS dependent MPTP opening, which may occur irrespective of a low matrix calcium concentration, may additionally contribute to this final event.
Minor comment At page 7 we read: “Notably, these experiments likely underestimate the effect on mitochondrial Ca2+ influx observed upon loss of the m-AAA protease, since the loss of the m-AAA protease also decreases ΔΨ (i.e., the main force driving mitochondrial Ca2+ influx), as revealed by the significant impairment of mitochondrial Ca2+ influx triggered by histamine stimulation (Maltecca et al., 2015) (Figures S6A–S6E)”. The reference is not appropriate, since in Maltecca et al., 2015 the reduced mitochondrial calcium uptake has been demonstrated in Afg3l2 knock-out Purkinje neurons upon challenge with KCl and not with histamine. We used histamine stimulation, which triggers IP3-mediated calcium release from ER, in Afg3l2 ko MEF in a previous publication (Maltecca F, De Stefani D, Cassina L, Consolato F, Wasilewski M, Scorrano L, Rizzuto R, Casari G. Respiratory dysfunction by AFG3L2 deficiency causes decreased mitochondrial calcium uptake via organellar network fragmentation. Hum Mol Genet. 2012, 21:3858-70. doi: 10.1093/hmg/dds214).
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On 2016 Oct 27, James Yeh commented:
Editor's Comment Obesity and Management of Weight Loss — Polling Results
James Yeh, M.D., M.P.H., and Edward W. Campion, M.D.
Obesity is increasingly prevalent worldwide, and about 40% of Americans meet the diagnostic criteria for obesity.[1] The goal of weight loss is to reduce the mortality and morbidity risks associated with obesity. Patients with a body-mass index (BMI) in the range that defines obesity (>30) have a risk of death that is more than twice that of persons with a normal BMI.[2] Obesity is also associated with increased risks of cardiovascular disease, diabetes, and several cancers. A recent study suggests that being overweight or obese during adolescence is strongly associated with increased cardiovascular mortality in adulthood.[3] Studies suggest that even a 5% weight loss may reduce the complications associated with obesity.[4]
In September 2016, we presented the case of Ms. Chatham, a 29-year-old woman with class I obesity (BMI, 32) who leads a fairly sedentary lifestyle, with frequent reliance on takeout foods and with infrequent physical activity.[5] Readers were invited to vote on whether to recommend initiating treatment with one of the FDA-approved drugs for weight loss along with lifestyle modifications or to recommend only nonpharmacologic therapies and maximizing lifestyle changes. The patient has no coexisting medical conditions, but her blood pressure is slightly elevated (144/81 mm Hg). In the past, Ms. Chatham has tried to lose weight using various diets, each time losing 10 to 15 lb (4.5 to 6.8 kg), but she has never been able to successfully maintain weight loss.
Over 85,000 readers viewed the Clinical Decisions vignette during the polling period, and 905 readers from 91 countries voted in the informal poll. The largest group of respondents (366) was from the United States or Canada, representing nearly 40% of the votes. A large majority of the readers (80%) voted against prescribing one of the FDA-approved medications for weight loss and instead recommended maximizing lifestyle modification and nonpharmacologic therapies first.
A substantial proportion of the 64 Journal readers who submitted comments expressed concern about the absence of efficacy data on long-term follow-up and about the side effects associated with current FDA-approved medications for weight loss. Some suggested that simply treating obesity with a prescription medication is shortsighted and that it is important to uncover patients’ motivations for existing lifestyle choices and for weight loss. The commenters emphasized the need for a multifaceted approach to obesity management that includes nutritional and psychological support, as well as stress management, with the goal of long-lasting improvement in exercise and eating habits that will lead to weight reduction and maintenance of a healthier weight.
Some commenters, noting the difficulty of lifestyle changes, felt that pharmacotherapy can be a complementary and reasonable part of a multidisciplinary treatment plan. Some wrote that obesity should be managed as a chronic disease is managed and that an inability to lose weight should not be seen as a disciplinary issue, especially given the importance of genetic and physiological factors. These commenters argued that the use of pharmacotherapy as part of the treatment plan to achieve weight loss should not be stigmatized.
Overall, the results of this informal Clinical Decisions poll indicate that a majority of the respondents think physicians should not initially recommend the use of an FDA-approved drug as part of a weight-loss strategy, at least not for a patient such as Ms. Chatham, and that many respondents were troubled by the current uncertainties about the long-term efficacy and safety of weight-loss drugs.
REFERENCES 1. Flegal KM, Kruzon-Moran D, Carroll MD, Fryar CD, Ogden CL. Trends in obesity among adults in the United States, 2005 to 2014. JAMA 2016;315:2284-91. 2. Global BMI Mortality Collaboration. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet 2016;388:776-86. 3. Twig G, Yaniv G, Levine H, et al. Body-mass index in 2.3 million adolescents and cardiovascular death in adulthood. N Engl J Med 2016;374:2430-40. 4. Kushner RF, Ryan DH. Assessment and lifestyle management of patients with obesity: clinical recommendations from systematic reviews. JAMA 2014;312:943-52. 5. Yeh JS, Kushner RF, Schiff GD. Obesity and management of weight loss. N Engl J Med 2016;375;1187-9.
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On 2016 Oct 22, Lydia Maniatis commented:
Part 1 This paper is all too similar to a large proportion of the vision literature, in which fussy computations thinly veil a hollow theoretical core, comprised of indefensible hypotheses asserted as fact (and thus implicitly requiring no justification), sometimes supported by citations that only weakly support them, if at all. The casual yet effective (from a publication point of view) fashion in which many authors assert popular (even if long debunked) fallacies and conjure up other pretexts for what are, in fact, mere measurements without actual or potential theoretical value is well on display here.
What is surprising in, perhaps, every case, is the willful empirical agnosia and lack of common sense, on every level – general purpose, method, data analysis - necessary to enable such studies to be conducted and published. A superficial computational complexity adds insult to injury, as many readers may wrongly feel they are not competent to understand and evaluate the validity of a study whose terms and procedures are so layered, opaque and jargony. However, the math is a distraction.
Unjustified and/or empirically false assumptions and procedures occur, as mentioned, at every level. I discuss some of the more serious ones below (this is the first of a series of comments on this paper).
- Misleading, theoretically and practically untenable, definitions of “3D tilt” (and other variables).
The terms slant and tilt naturally refer to a geometrical characteristic of a physical plane or volume (relative to a reference plane). The first sentence of Burge et al’s abstract gives the impression that we are talking about tilt of surfaces: “Estimating 3D surface orientation (slant and tilt) is an important first step toward estimating 3D shape. Here, we examine how three local image cues …should be combined to estimate 3D tilt in natural scenes.” As it turns out, the authors perform a semantic but theoretically pregnant sleight of hand in the switch from the phrase “3D surface orientation (slant and tilt)” to the phrase “3D tilt” (which is also used in the title).
The obvious inference from the context is that the latter is a mere short-hand for the former. But it is not. In fact, as the authors’ finally reveal on p. 3 of their introduction, their procedure for estimating what they call “3D tilt” does not allow them to correlate their results to tilt of surfaces: “Our analysis does not distinguish between the tilt of surfaces belonging to individual objects and the tilt (i.e. orientation [which earlier was equated with “slant and tilt”]) of depth discontinuities…We therefore emphasize that our analysis is best thought of as 3D tilt rather than 3D surface tilt estimation.”
“3D tilt” is, in effect, a conceptually incoherent term made up to coincide with the (unrationalised) procedure used to arrive at certain measures given this label. I find the description of the procedure opaque, but as I am able to understand it, small patches of images are selected, and processed to produce “3D tilt” values based on range values collected by a range finder within that region of space. The readings within the region can be from one, two, three, four, or any number of different surfaces or objects; the method does not discriminate among these cases. In other words, these local “3D tilt values” have no necessary relationship to tilt of surfaces (let alone tilt of objects, which is more relevant (to be discussed) and which the authors don’t address even nominally). We are talking about a paradoxically abstract, disembodied definition of “3D tilt.” As a reader, being asked to “think” of the measurements as representing “3D tilt” rather than “3D surface tilt” doesn’t help me understand either how this term relates, in any useful or principled way, to the actual physical structure of the world, nor to the visual process that represents this world. The idea that measuring this kind of “tilt” could be useful to forming a representation of the physical environment, and that the visual system might have evolved a way to estimate these intrinsically random and incidental values, is an idea that seems invalid on its face - and the authors make no case for it.
They then proceed to measure 3 other home-cooked variables, in order to search for possible correlations between these and “3D tilt.” These variables are also chosen arbitrarily, i.e. in the absence of a theoretical rationale, based on: “simplicity, historical precedence, and plausibility given known processing in the early visual system.” (p. 2). Simplicity is not, by itself, a rationale – it has to have a rational basis. At first glance, at least the third of these reasons would seem to constitute a shadow of a theoretical rationale, but it is based on sparse, premature and over-interpreted physiological data primarily of V1 neuron activity. Furthermore, the authors’ definitions of their three putative cues: disparity gradient, luminance gradient, texture gradient, are very particular, assumption-laden, paradoxical, and unrationalised.
For example, the measure of “texture orientation” involves the assumption that textures are generally composed of “isotropic [i.e. circular] elements” (p. 8). This assumption is unwarranted to begin with. Given, furthermore, that the authors’ measures at no point involve parsing the “locations” measured into figures and grounds, it is difficult to understand what they can mean by the term “texture element.” Like tilt, reference to an “isotropic texture element” implies a bounded, discrete area of space with certain geometric characteristics and relationships. It makes no sense to apply it to an arbitrary set of pixel luminances.
Also, as in the case of “3D tilt” the definition of “texture gradient” is both arbitrary and superficially complex: “we define [the dominant orientation of the image texture] in the Fourier domain. First, we subtract the mean luminance and multiply by (window with) the Gaussian kernel above centered on (x, y). We then take the Fourier transform of the windowed image and comute the amplitude spectrum. Finally, we use singular value decomposition ….” One, two, three….but WHY did you make these choices? Simplicity, historical precedence, Hubel and Wiesel…?
If, serendipitously, the authors’ choices of things to measure and compare had led to high correlations, they might have been justified in sharing them. But as it turns out, not surprisingly, the correlations between “cues” and “tilt” are “typically not very accurate.” Certain (unpredicted) particularities of the data which to which the authors speculatively attribute theoretical value (incidentally undermining one of their major premises) will be discussed later.
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On 2016 Dec 28, Lydia Maniatis commented:
Cherniawsky and Mullen’s (2016) article lies well within the perimeter of a school of thought that, despite its obvious intellectual and empirical absurdity, is popular within the vision science community.
The school persists, and is relentlessly prolific, because it has insulated itself from the possibility of falsification, mainly by ignoring both fact and reason.
Explanatory schemes are concocted with respect to a narrow set of stimuli and conditions. Data generated under this narrow set of conditions are always interpreted in terms of the narrow scheme of assumptions, via permissive post hoc modeling. When, as here, results contradict expectation, additional ad hoc assumptions are made with reference to the specific, narrow type of stimuli used, which then, of course, may subsequently be corroborated, more or less, using those same stimuli or mild variants thereof.
The process continues ad infinitum via the same ad hoc route. This is the reason that, as Kingdom (2011) has noted, the study of lightness, brightness and transparency (and I would add, vision science in general) is divided into camps “each with its own preferred stimuli and methodology” and characterized by “ideological divides.“ The term “ideological” is highly appropriate here, as it indicates a refusal to face facts and arguments that contradict or challenge the preferred view. It is obviously antithetical to the scientific attitude and, unfortunately, very typical of virtually all of contemporary vision science.
The title of this paper ”The whole is other than the sum...” indicates that a prediction of “summation” failed even under the gentle treatment it received. The authors don’t quite know what to make of their results, but a conclusion of “other” is enough by today’s standards.
The ideological camp to which this article belongs is a scandal on many counts. First, it adopts the view that there are certain figures whose retinal projections trigger visual processes such that the ultimate percept directly reflects local “low-level” processes. More specifically, it reflects “low-level” processes as they are currently (and crudely) understood. The figures supposed to have this quality are those for which the appropriate “low-level” story du jour has been concocted.
The success of the method is well-described by Graham (1997, discussed in PubPeer), who notes that countless experiments were "consistent" with the behavior of V1 neurons at a time when V1 had only begun to be explored and when researchers were unaware not only of the complexities of V1 but also of the many hierarchically higher-level and processes that intervene between retina and percept. This amazing success is rationalized (if we may use the term loosely) by Graham, who with magical thinking reckons that under certain conditions the brain becomes “transparent” down to the initial processing levels. Teller (1984) had earlier (to no apparent effect) described such a view as “the nothing mucks it up proviso,” and pointed out the obvious logical problems.
Cherniawsky and Mullen premise their article on this view with their opening sentence: “Two-dimensional orthogonal gratings (plaids) are a useful tool in the study of complex form perception, as early spatial vision is well described by responses to simple one-dimensional sinusoidal gratings…” In fact, the “one-dimensional sinusoidal gratings” in question typically produce 3D percepts of light and shadow, and the authors’ plaids in Figure 1 appear curved and partially obscured by a foggy overlay. So as illogical as the transparent brain hypothesis is to begin with, the stimuli supposed to tap into lower level processes aren’t even consistent with a strictly “low-level” interpretive process.
The uninitiated might wonder why the authors use the term “spatial vision.” It is because they have uncritically adopted the partner of the transparent brain hypothesis, the view that the early visual processes perform a Fourier analysis on the retinal projection. It is not clear that this is at all realistic at the physiological level, but there is also no apparent functional reason for such a challenging process, as it would in no way further the achievement of the goal of organizing the incoming light into figures and grounds as the basis for further interpretation leading to a (usually) veridical representation of the environment. The Fourier conceit is, of course, maintained by employing sinusoidal gratings while ignoring their actual perceptual effects. That is, the sinusoidal gratings and combinations thereof are said to tap into the low-level frequency channels, which then determine contrast via summation, inhibition, etc, (whatever post hoc interpretation the data of any particular experiment seem to require). These contrast impressions, though experienced in the context of, e.g. impressions of partially-shadowed tubes, are never considered with respect to these complex 3D percepts. Lacking necessary interpretive assumptions, investigators are reduced to describing their results in terms of “other,” precisely described, but theoretically unintelligible and tangled effects.
The idea that “summation” of local neural activities can explain perception is contradicted by a million cases, and counting, including the much-loved sinusoidal gratings and their shape-from-shading effects. But ideology is stronger and, apparently, good enough for vision science today.
Finally, the notion of “detectors” is a staple of this school and the authors’ discussion; for a discussion of why this concept is untenable, please see Teller (1984).
p.s. As usual, I’ll ask why its ok for an author to be one of a small number of subjects, the rest of whom are described as “naïve.” If it’s important to be naïve, then…
Also, why use forced choices, and thus inject more uncertainty than necessary into the results? It’s theoretically possible that observers never see what you think they’re seeing…Obviously, if you’re committed to interpreting results a certain way, it’s convenient to force the data to look a certain way…
Also, no explanation is given for methodological choices, e.g. the (very brief) presentation times.
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On 2017 Feb 04, DAVID LUDWIG commented:
Boiling down his comment of 3 Feb 2017, Hall disputes that the metabolic process of adapting to a high-fat/low-carbohydrate diet confounds interpretation of his and other short term feeding studies. If we can provide evidence that this process could take ≥ 1 week, the last leg of his attack on the Carbohydrate-Insulin Model collapses. Well, a picture is worth a thousand words, and here are 4:
For convenience, these figures can be viewed at this link:
Owen OE, 1983 Figure 1. Ketones are, of course, the hallmark of adaptation to a low-carbohydrate ketogenic diet. Generally speaking, the most potent stimulus of ketosis is fasting, since the consumption of all gluconeogenic precursors (carbohydrate and protein) is zero. As this figure shows, the blood levels of each of the three ketone species (BOHB, AcAc and acetone) continues to rise for ≥3 weeks. Indeed, the prolonged nature of adaptation to complete fasting has been known since the classic starvation studies of Cahill GF Jr, 1971. It stands to reason that this process might take even longer on standard low-carbohydrate diets, which inevitably provide ≥ 20 g carbohydrate/d and substantial protein.
Yang MU, 1976 Figure 3A. Among men with obesity on an 800 kcal/d ketogenic diet (10 g/d carbohydrate, 50 g/d protein), urinary ketones continued to rise for 10 days through the end of the experiment, and by that point had achieved levels equivalent only to those on day 4 of complete fasting. Presumably, this process would be even slower with a non-calorie restricted ketogenic diet (because of inevitably higher carbohydrate and protein content).
Vazquez JA, 1992 Figure 5B. On a conventional high-carbohydrate diet, the brain is critically dependent on glucose. With acute restriction of dietary carbohydrate (by fasting or a ketogenic diet), the body obtains gluconeogenic precursors by breaking down muscle. However, with rising ketone concentrations, the brain becomes adapted, sparing glucose. In this way, the body shifts away from protein to fat metabolism, sparing lean tissue. This phenomenon is clearly depicted among women with obesity given a calorie-restricted ketogenic diet (10 g carbohydrate/d) vs a nonketogenic diet (76 g carbohydrate/d), both with protein 50 g protein/d. For 3 weeks, nitrogen balance was strongly negative on the ketogenic diet compared to the non-ketogenic diet, but this difference was completely abolished by week 4. What would subsequently happen? We simply can’t know from the short-term studies.
Hall KD, 2016 Figure 2B. Hall’s own study shows that the transient decrease in rate of fat loss upon initiation of the ketogenic diet accelerates after 2 weeks.
The existence of this prolonged adaptive process explains why metabolic advantages for low-fat diet are consistently seen in very short metabolic studies. But after 2 to 4 weeks, advantages for low-carbohydrate diets begin to emerge, as summarized in my comment of 3 Feb 2017, below.
Fat adaptation on low-carbohydrate diets has admittedly not been thoroughly studied, and its duration may differ among individuals and between experimental conditions. Nevertheless, there is strong reason to think that short feeding studies (i.e., < 3 to 4 weeks) have no relevance to the long-term effects of macronutrients on metabolism and body composition.
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On 2017 Jan 21, Clive Bates commented:
How did the author manage to publish a paper with the title "E-cigarettes: Are they as safe as the public thinks?", without citing any data on what the public actually does think? There is data in the National Cancer Institute's HINTS survey 2015. This is what it says:
Compared to smoking cigarettes, would you say that electronic cigarettes are…
- 5.3% say much less harmful
- 20.6% say less harmful
- 32.8% say just as harmful
- 2.7% say more harmful
- 2.0% say much more harmful
- 1.2% have never heard of e-cigarettes
- 33.9% don’t know enough about these products
Which brings me to the main issue with the paper. The author claims that there is insufficient knowledge to determine if these products are safer than cigarettes. This is an extraordinary and dangerous claim given what is known about e-cigarettes and cigarettes. It is known with certainty that there are no products of combustion of organic material (i.e tobacco leaf) in e-cigarette vapour - this is a function of the physical and chemical processes involved. We also know that products of combustion cause almost all of the harm associated with smoking. There is also extensive measurement of harmful and potentially harmful constituent of cigarette smoke and e-cigarette aerosol showing many are not detectable or present at levels two orders of magnitude lower in the vapour aerosol (e.g. see Farsalinos KE, 2014, Burstyn I, 2014). So the emissions are dramatically less toxic and exposures much lower.
The author provides a familiar non-sequitur: "There are no current studies that prove that e-cigarettes are safe". There never will be. Firstly because it is impossible to prove something to be completely safe, and almost nothing is. Secondly, no serious commentators claim they are completely safe, just very much safer than smoking. Hence the term 'harm reduction' to describe the benefits of switching to these products.
This view commands support in the expert medical profession. The Royal College of Physicians (London) assessed the toxicology evidence in its 2016 report Nicotine without smoke: tobacco harm reduction and concluded:
Although it is not possible to precisely quantify the long-term health risks associated with e-cigarettes, the available data suggest that they are unlikely to exceed 5% of those associated with smoked tobacco products, and may well be substantially lower than this figure. (Section 5.5 page 87)
This is a carefully measured statement that aims to provide useful information to both users of the products and health and medical professionals while reflecting residual uncertainty. It contrasts with the author's information leaflet for patients, which even suggests there is no basis for believing e-cigarettes to be safer than smoking:
If you are smoking and not planning to quit, we don't know if e-cigarettes are safer. Talk to your health care provider.
But we do know beyond any reasonable doubt that e-cigarettes are very much safer - the debate is whether they are 90% safer or 99.9% safer than smoking. Regrettably, only 5.3% of American adults correctly believe that e-cigarettes are very much less harmful than smoking, while 37% incorrectly think they are as harmful or more harmful (see above). The danger with these misperceptions of risk is that they affect behaviour, causing people to continue to smoke when they might otherwise switch to much safer vaping. The danger with a paper like this and its patient-facing leaflet is that it nurtures these harmful risk misperceptions and becomes, therefore, a vector for harm.
To return to the author's title question: E-Cigarettes: Are They as Safe as the Public Thinks?. The answer is: "No, they are very much safer than the public thinks".
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On 2017 Jan 21, Clive Bates commented:
There are at least five problems with this paper:
First, the authors simply assume that the pro-e-cigarette tweets are wrong and need their corrective input. What if users are right to be positive? The authors have not demonstrated any material risk from vapour aerosol. To the extent that there is evidence of exposure the levels so low as to be very unlikely to be a health concern. The presence of a hazardous agent does not in itself imply a risk to health, there has to be sufficient exposure to be toxicologically relevant.
Second, they have also not considered what harmful effect that their potentially misleading 'health education messages' may have. For example, by exaggerating a negligible risk they may be discouraging people from e-cigarette use, and potentially causing relapse to smoking and reducing the incentive to switch - thus doing more harm than had they not intervened. We already know the vast majority of smokers think e-cigarettes are much more dangerous than the toxicological profile of the aerosol suggests - see National Cancer Institute HINTS data. The authors' ideas would aggravate these already highly damaging misperceptions of risk.
Third, as so often happens with tobacco control research, the authors make a policy proposal for which their paper comes nowhere close to providing an adequate justification.
Public health and regulatory agencies could use social media and traditional media to disseminate the message that e-cigarette aerosol contains potentially harmful chemicals and could be perceived as offensive.
They have not even studied the effects of the messages they are recommending on the target audience or tested such messages through social media. If they did, they would discover that users are not passive or compliant recipients of health messages, especially if they suspect they are wrong or ill-intentioned. Social media creates two-way conversations in which often very well-informed users will respond persuasively to what they find to be poorly informed or judgemental health messages. Until the authors have tested a campaign of the type they have in mind, they have no basis for recommending that agencies spend public money in this way.
Fourth, the authors suggest that users should be warned by public health agencies that "e-cigarette aerosol ... could be perceived as offensive". If there were warnings from public health and regulatory agencies about everything that could be perceived as offensive by someone, then we would be inundated with warnings. This is not a reliable basis or priority for public health messaging. Given the absence of any demonstrable material risk from e-cigarette aerosol, the issue is one of etiquette and nuisance. This does not require government intervention of any sort. Vaping policy in any public or private place should be a matter for the owners or managers, who may not find it offensive nor wish to offend their clientele. It is not a matter for legislators, regulators or health agencies.
Fifth (and with thanks to Will Moy's tweet), the work is pointless and wasteful. Who cares what people are saying on twitter about e-cigarettes and secondhand aerosol exposure? Why is this even a subject worthy of study and what difference could it make to any outcomes that are important for health or any other policy? What is the rationale for spending research funds on this form of vaguely creepy social media surveillance?
Updated 21-Jan-17 with fifth point.
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On 2017 Feb 08, Lydia Maniatis commented:
To make clear what Adamian and Cavanagh (2017) do, and what they don’t do, in this publication. What they don’t do is to test a hypothesis. What they do is present a casual, ad hoc explanation of the Frohlich effect based on the results of past experiments, which they replicate here. The proposal remains untested. Even the ad hoc, untested assumptions (“we assume that the critical delay in producing the Fröhlich effect is not just the delay of attention in arriving at the target but also the time a saccade would then need to land on the target, if one were executed;”) can’t explain the results of their experiments, requiring more ad hoc proposals about complex processes: “The results suggest that the simultaneous onsets may be held in iconic memory and the cued motion trajectory can be retrieved if the cue arrives soon enough;” “A late SOA implies a longer memory retention period, and that means that the reported shifts could arise from working memory limitations and might not be perceptual in nature.”
Is Adamian and Cavanagh’s assumption that “the critical delay is not just the delay of attention….but also the time a saccade would then need to land on the target…” testable?
How would one go about testing it, as well as the additional assumptions the authors feel obliged to make with respect to memory?
Why didn’t the authors attempt to test their proposal to begin with, rather than simply performing replications that, even if successful, could do no more than leave the issue unresolved? They have not even proposed possible tests.
Obviously, replication was the safer choice, but one, again, that is essentially uninformative vis a vis an ad hoc proposal. It should be clear that the subject of eye movements and their role in perception is extremely complex and that casual speculations are unlikely to be borne out, if properly tested.
I think Adamian and Cavanagh’s proposal is so vague, the confounds so many, and (least of all, at present) the technical demands so great, that it cannot be tested. If all of the main and subsidiary assumptions, and their implications, were clarified enough to allow them to be critically assessed for logical coherence and consistency with other known facts, it might well fail at this stage, obviating the need for experimental tests.
Of course, I could be wrong in the present case; the authors may intend, post-replication, to attempt to concretize and subject their proposal to a genuine test; that would be genuinely refreshing.
I would note, as an afterthought, the uninformative nature of the title of the article, which is typical of many vision science articles and reflects the essentially uninformative nature of the work itself. The title tells us what the article is about, but not what it concluded or implied.
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On 2017 Nov 03, Elisabeth Schramm commented:
In reply to a comment by Falk Leichsenring
Allegiance effects controlled
Elisabeth Schramm, PhD; Levente Kriston, PhD; Ingo Zobel, PhD; Josef Bailer, PhD; Katrin Wambach, PhD; Matthias Backenstrass, PhD; Jan Philipp Klein, MD; Dieter Schoepf, MD; Knut Schnell, MD; Antje Gumz, MD; Paul Bausch, MSc; Thomas Fangmeier, PhD; Ramona Meister, MSc; Mathias Berger, MD; Martin Hautzinger, PhD; Martin Härter,MD, PhD
Corresponding Author: Elisabeth Schramm, PhD, Department of Psychiatry, Faculty of Medicine, University of Freiburg, Hauptstrasse 5, 79104 Freiburg, Germany (elisabeth.schramm@uniklinik-freiburg.de)
We acknowledge the comment of Drs. Steinert and Leichsenring (1) on our study (2) reasoning that our findings may at least in part be attributed to allegiance effects. Unfortunately, they provide neither a clarification of what they exactly refer to with the term “allegiance effects” nor a specific description of the presumed mechanisms (chain of effects) through which they think allegiance may have influenced our results. In fact, as specified both in the trial protocol (3) and the study report (2), we took a series of carefully safeguarded measures to minimize bias. Unlike stated in the comment, training and supervision of the study therapists and the center supervisors were performed by qualified and renowned experts for both investigated approaches (Martin Hautzinger for Supportive Psychotherapy and Elisabeth Schramm for Cognitive Behavioral Analysis System of Psychotherapy). Moreover, none of them has been involved in treating any study patients in this trial. We are confident that any possible allegiance of the participating researchers, therapists, supervisors, or other involved staff towards any, both, or none of the investigated interventions is very unlikely to have been able to surmount all of the implemented measures against bias and to affect the results substantially.
References
(1) Steinert C, Leichsenring F. The need to control for allegiance effects in psychotherapy research. PubMed Commons. Sep 08 2017
(2) Schramm E, Kriston L, Zobel I, Bailer J, Wambach K, Backenstrass M, Klein JP, Schoepf D, Schnell K, Gumz A, Bausch P, Fangmeier T, Meister R, Berger M, Hautzinger M, Härter M. Effect of Disorder-Specific vs Nonspecific Psychotherapy for Chronic Depression: A Randomized Clinical Trial. JAMA Psychiatry. Mar 01 2017; 74(3): 233-242
(3) Schramm E, Hautzinger M, Zobel I, Kriston L, Berger M, Härter M. Comparative efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus supportive psychotherapy for early onset chronic depression: design and rationale of a multisite randomized controlled trial. BMC Psychiatry. 2011;11:134
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On 2017 Feb 15, Lydia Maniatis commented:
I don’t think the authors have addressed the unusual aspects of the dress in saying that “The perceived colors of the dress are due to (implicit) assumptions about the illumination.” As they note themselves, “This is exactly what would be predicted from classical color science…”
The spectrum of light reflected to our eye is a function of the reflectance properties of surfaces and the spectrum of the illumination; both are disambiguated on the basis of implicit assumptions, and both are represented in the percept. The two perceptual features (surface color and illumination) are two sides of the same coin: Just as we can say that seeing a surface as having color x of intensity y is due to assumptions about the color and intensity of the illuminants, so we can say that seeing illumination of color x and intensity y is due to implicit assumptions about the reflectance (how much light they reflect) and the chromaticity (which wavelengths they reflect/absorb) of the viewed surfaces. We haven’t explained anything unless we can explain both things at the same time.
The authors are choosing one side of the perceptual coin – the apparent illumination – and claiming to have explained the other. Again, it’s a truism to say that seeing a patch of the dress as color “x” implies we are seeing it as being under illumination “y,” while perceiving the patch as a different color means perceiving a different illumination. This doesn’t explain what makes the dress unusual - why it produces different color/illumination impressions in different people.
The authors seem to want to take the “experience” route (“prior experiences may influence this perception”); this is logically and empirically untenable, as has been shown and argued innumerable times in the vision literature. For one thing, such a view is circular, since what we see in the first place is a product of the assumptions implicit in the visual process. It’s not as though we see things first, and then adopt assumptions that allow us to see it…In addition, why would such putative experience influence only the dress, and not each and every percept? (The same objection applies to explanations in terms of physiological differences). Again, the question of what makes the dress special is left unaddressed.
It’s odd that, for another example of such a phenomenon, vision researchers need to turn to “poppunkblogger.” If they understood it in principle, then they would be able to construct any number of alternative versions. Even if they could show the perception of the dress to be experience-based (which, again, is highly unlikely to impossible), this would not not help; they would still be at a loss to explain why different people see different versions of one image and not most others. To understand the special power of the dress, they need at a minimum to analyze its structure, not only in terms of color but in terms of shape, which is the primary mediator of all aspects of perception. Invoking “scene interpretation” and “the particular color distributions” are only placeholders for all the things the authors don’t understand.
The construction of images that show that the dress itself can produce consistent percepts is genuinely interesting, but it is a problem that the immediate backgrounds are not the same (e.g. arm placements). This produces confounds. The claim that these confounds are designed to produce the opposite effect of what is seen, based on contrast effects, is not convincing, since the idea that illusions involving transparency/illumination are based on local contrast effects is a claim that is easy to falsify empirically, and has been falsified. So we are dealing with unanalyzed confounds, and one has to wonder how much blind trial and error was involved in generating the images.
Finally, I’m wondering why a cutout of the dress wasn’t also placed against a plain background as a control; what happens in this case? Has this been done yet?
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On 2017 Nov 08, Cicely Saunders Institute Journal Club commented:
We selected and discussed this paper at our monthly journal club on 1st November 2017.
The paper generated a lot of discussion and we felt that this was an important concept, especially for clinicians, to think about. The topic of QALYs was unfamiliar to some of us and we found that the authors explained it very clearly in the paper. We were intrigued by the use of an integrative review method and discussed this at length. It may have been helpful to read more explanation of this method and know how it differs from other types of review methods. We also wondered about some of the inclusion/exclusion criteria such as the exclusion of reviews and the decision making process for the theoretical papers included. We enjoyed discussing the themes which emerged from this paper and the wider debate around the most appropriate measures for palliative care populations, particularly in light of the recent paper by Dzingina et al. 2017 (https://www.ncbi.nlm.nih.gov/pubmed/28434392). We feel this paper will be a useful educational resource.
Commentary by Dr. Nilay Hepgul & Dr. Deokhee Yi on behalf of researchers at Cicely Saunders Institute of Palliative Care, Policy & Rehabilitation, King’s College London.
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On 2017 Mar 04, Lydia Maniatis commented:
What Ratnasingam and Anderson are doing here is analogous to this imaginary example: Let’s say that I have a strong allergy to food x, a milder one to food y, none to food z, and so on, and that my allergies produce various symptoms. Let’s assume also that some of these effects can be interpreted fairly straightforwardly in terms of formal structural relationships between my immune system and the molecular components of the foods, and others not. For these others, we can assume either a functional rationale or perhaps consider them a side effect of structure or function. We don’t know yet. For other individuals, other allergy/food combinations have corresponding effects. Again, if we know something about the individual we can predict some of the allergic reactions based on known principles.
How much sense would it make now, to conduct a study whose goal is: “to articulate general principles that can predict when the size of an allergic reaction will be large or small for arbitrarily chosen food/patient combinations…. What (single) target food generates the greatest allergic difference when ingested by two arbitrarily chosen patients?” (“Our goal is to articulate general principles that can predict when the size of induction will be large or small for arbitrarily chosen pairs of center-surround displays…. What (single) target color generates the greatest perceptual difference when placed on two arbitrarily chosen surround colors?”)
Furthermore, having gotten their results, our researchers now decline to attempt to interpret them in terms of the nuanced understanding already available.
The most striking thing about the present study is that a researcher who has done (unusually) good work in studying the role of structure and chromatic/lightness relationships in the perception of color is now throwing all this insight overboard, ignoring what is known about these factors and lumping them all together, in the hope of arriving at some magic, universal formula for “simultaneous contrast” that is blind to them. Obviously the effort is bound to fail, and the title – framed as a question, not an answer – is evidence of this. Here is a sample, revealing caveat:
“Finally, it should also be noted that although some of our comparisons involved target–surround combinations in which some targets can appear as both an increment and decrement relative to the two surrounds, which would induce differences in both hue and saturation (e.g., red and green). Such pairs may be rated as more dissimilar than two targets of the same hue (e.g., red and redder), but it could be argued that this does not imply that the size of simultaneous contrast is larger in these conditions. However, it should be noted that such conditions are only a small subset of those tested herein.” Don’t bother us with specifics, we’re lumping.
As the authors discuss in their introduction, studies (treating “simultaneous contrast” in a crude, structure-and-relationship-blind way) produce conflicting results: “The conflicting empirical findings make it difficult to articulate a general model that predicts when simultaneous contrast effects will be large or small, since there is currently no model that captures how the magnitude of induction varies independently of method used…. “ Of course. When you don’t take into account relevant principles, and control for relevant factors, your results will always mystify you.
The conflation between, or refusal to distinguish explicitly, cases in which transparency arises and in which it does not arise is really inexplicable.
"The suggestion that the strongest forms of simultaneous contrast arise in conditions that induce the perception of transparency gains conceptual support from evidence showing that transparency can generate dramatic transformations in both perceived lightness and color..." But the contextual conditions that produce transparency are really quite...transparent...There's no clear reason to lump these with situations that are perceptually and logically distinct.
Also: "In simultaneous contrast displays, the targets and surrounds are also texturally continuous, in the sense that they are both uniform, but there are no strong geometric cues for the continuation of the surround through the target region of the kind known to give rise to vivid percepts of transparency (such as contours or textures). It is therefore difficult to generate a prediction for when transparency should be induced in homogeneous center-surround patterns, or how the induction of transparency should modulate the chromatic appearance of a target as a function of the chromatic difference between a target and its surround."
First, I'll pay him the compliment of saying that I don't think that it would be that difficult for Anderson to generate predictions for when transparency should occur...(I think even I could do it). Second, if this theoretical gap really exists, then this is the problem that should be addressed, not "what happens if we test a lot of random combinations and average the results." It might be useful to take into consideration a demo devised by Soranzo, Galmonte & Agostini (2010) which is a case of transparency effect that lacks the "cues" mentioned here - and thus by these authors' criteria qualifies as a basic simultaneous contrast display. (I don't think its that difficult to explain, but maybe I haven't thought about it enough.)
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On 2017 Aug 06, John Greenwood commented:
(cross-posted from Pub Peer, comment numbers refer to that discussion but content is the same)
To address your comments in reverse order -
Spatial vision and spatial maps (Comment 19):
We use the term “spatial vision” in the sense defined by Russell & Karen De Valois: “We consider spatial vision to encompass both the perception of the distribution of light across space and the perception of the location of visual objects within three-dimensional space. We thus include sections on depth perception, pattern vision, and more traditional topics such as acuity." De Valois, R. L., & De Valois, K. K. (1980). Spatial Vision. Annual Review of Psychology, 31(1), 309-341. doi:doi:10.1146/annurev.ps.31.020180.001521
The idea of a "spatial map” refers to the representation of the visual field in cortical regions. There is extensive evidence that visual areas are organised retinotopically across the cortical surface, making them “maps". See e.g. Wandell, B. A., Dumoulin, S. O., & Brewer, A. A. (2007). Visual field maps in human cortex. Neuron, 56(2), 366-383.
Measurement of lapse rates (Comments 4, 17, 18):
There really is no issue here. In Experiment 1, we fit a psychometric function in the form of a cumulative Gaussian to responses plotted as a function of (e.g.) target-flanker separation (as in Fig. 1B), with three free parameters: midpoint, slope, and lapse rate. The lapse rate is 100-x where x is the asymptote of the curve. It accounts for lapses (keypress errors etc) when performance is otherwise high - i.e. it is independent of the chance level. In this dataset it is never about 5%. However its inclusion does improve estimate of slope (and therefore threshold) which we are interested in. Any individual differences are therefore better estimated by factoring out individual differences in lapse rate. Its removal does not qualitatively affect the pattern of results in any case. You cite Wichmann and Hill (2001) and that is indeed the basis of this three-parameter fit (though ours is custom code that doesn’t apply the bootstrapping procedures etc that they use).
Spatial representations (comment 8):
We were testing the proposal that crowding and saccadic preparation might depend on some degree of shared processes within the visual system. Specific predictions for shared vs distinct spatial representations are made on p E3574 and in more detail on p E3576 of our manuscript. The idea comes from several prior studies arguing for a link between the two, as we cite, e.g.: Nandy, A. S., & Tjan, B. S. (2012). Saccade-confounded image statistics explain visual crowding. Nature Neuroscience, 15(3), 463-469. Harrison, W. J., Mattingley, J. B., & Remington, R. W. (2013). Eye movement targets are released from visual crowding. The Journal of Neuroscience, 33(7), 2927-2933.
Bisection (Comments 7, 13, 15):
Your issue relates to biases in bisection. This is indeed an interesting area, mostly studied for foveal presentation. These biases are however small in relation to the size of thresholds for discrimination, particularly for the thresholds seen in peripheral vision where our measurements were made. An issue with bias for vertical judgements would lead to higher thresholds for vertical vs. horizontal judgements, which we don’t see. The predominant pattern in bisection thresholds (as with the other tasks) is a radial/tangential anisotropy, so vertical thresholds are worse than horizontal on the vertical meridian, but better than horizontal thresholds on the horizontal meridian. The role of biases in that anisotropy is an interesting question, but again these biases tend to be small relative to threshold.
Vernier acuity (Comment 6):
We don’t measure vernier acuity, for exactly the reasons you outline (stated on p E3577).
Data analyses (comment 5):
The measurement of crowding/interference zones follows conventions established by others, as we cite, e.g.: Pelli, D. G., Palomares, M., & Majaj, N. J. (2004). Crowding is unlike ordinary masking: Distinguishing feature integration from detection. Journal of Vision, 4(12), 1136-1169.
Our analyses are certainly not post-hoc exercises in data mining. The logic is outlined at the end of the introduction for both studies (p E3574).
Inclusion of the authors as subjects (Comment 3):
In what way should this affect the results? This can certainly be an issue for studies where knowledge of the various conditions can bias outcomes. Here this is not true. We did of course check that data from the authors did not differ in any meaningful way from other subjects (aside from individual differences), and it did not. Testing (and training) experienced psychophysical observers takes time, and authors tend to be experienced psychophysical observers.
The theoretical framework of our experiments (Comments 1 & 2):
We make an assumption about hierarchical processing within the visual system, as we outline in the introduction. We test predictions that arise from this. We don’t deny that feedback connections exist, but I don’t think their presence would alter the predictions outlined at the end of the introduction. We also make assumptions regarding the potential processing stages/sites underlying the various tasks examined. Of course we can’t be certain about this (and psychophysics is indeed ill-poised to test these assumptions) and that is the reason that no one task is linked to any specific neural locus, e.g. crowding shows neural correlates in visual areas V1-V4, as we state (e.g. p E3574). Considerable parts of the paper are then addressed at considering whether some tasks may be lower- or higher-level than others, and we outline a range of justifications for the arguments made. These are all testable assumptions, and it will be interesting to see how future work then addresses this.
All of these comments are really fixated on aspects of our theoretical background and minor details of the methods. None of this in any way negates our findings. Namely, there are distinct processes within the visual system, e.g. crowding and saccadic precision, that nonetheless show similarities in their pattern of variations across the visual field. We show several results that suggest these two processes to be dissociable (e.g. that the distribution of saccadic errors is identical for trials where crowded targets were correctly vs incorrectly identified). If they’re clearly dissociable tasks, how then to explain the correlation in their pattern of variation? We propose that these properties are inherited from earlier stages in the visual system. Future work can put this to the test.
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On 2017 Apr 24, Lydia Maniatis commented:
This article’s casual approach to theory is evident in the first few sentences. After noting irrelevantly, that “Since their introduction (Wilkinson, Wilson, & Habak, 1998), RF patterns have become a popular class of stimuli in vision science, commonly used to study various aspects of shape perception,” the authors immediately continue to say that “Theoretically, RF pattern detection (discrimination against a circle) could be realized either by local filters matched to the parts of the pattern, or by a global mechanism that integrates local parts operating on the scale of the entire pattern.” No citation is offered for this vague and breezy assertion, which begs a number of questions.
How did we jump from “shape perception” to “RF detection against a circle”? How is the latter related to the former?
Is the popularity of a pattern sufficient reason to assume that there exist special mechanisms – special detectors, or filters – tailored to its characteristics? Is there any basis whatsoever for this assertion?
Given that we know that the whole does determine the parts perceived, why are we talking about integration of “local” elements? And how do we define local? Doesn’t a piece of a shape also consist of smaller pieces, etc? What is the criterion for designating part and whole in a stimulus pattern (as opposed to the fully-formed percept)?
Apparently, there have been many ‘models’ proposed for special mechanisms for “RF detection against a circle,” addressing the question in these local/local-to-global terms. Could the mechanism involve maximum curvature integration, tangent orientations at inflection points, etc.? These simply take for granted the underlying assumption that there are special “filters” for “RF discrimination against a circle.” The only question is to what details of the figure are these mechanisms attuned.
What if we were dealing with different types of shapes? What if the RF boundary shape were formed by different sized dots, or dashes, or rays of different lengths radiating from a center? Would we be talking about dot filters, or line length filters? Why put RF patterns in general, and RF patterns of this type in particular, on such an explanatory pedestal?
More critically, how is it possible to leverage such patterns to dissect the neural processes underlying perception? When I look at one of these patterns, I don’t have any trouble distinguishing it from a circle. What can this tell me about the underlying process?
A subculture of vision science has opted to uncritically embrace the view that underlying processes can be inferred quite straightforwardly on the basis of certain procedures that mimic the general framework of signal detection. This view is labeled “signal detection theory” or SDT, but “theory” is overstating it. As noted in my earlier comment, Schmidtmann and Kingdom (2017) never explain why they make what, to a naïve observer, must seem very arbitrary methodological choices, nor does their main reference, Wilkerson, Wilson and Habak (1998). So we have to go back further to find some suggestion of a rationale.
The founding fathers of the aforementioned subculture include Swets, Tanner and Birdsall (e.g. 1961). As may be seen from a quote from that article (below), the framing of the problem is artificial; major assumptions are adopted wholesale; “perception” is casually converted to “detection” (in order to fit the analogy of a radar observer attempting to guess which blip is the object of interest).
“In the fundamental detection problem, an observation is made of events occurring in a fixed interval of time and a decision is made; based on this observation, whether the interval contained only the background interference or a signal as well. The interference, which is random, we shall refer to as noise and denote as N; the other alternative we shall term signal plus noise, SN. In the fundamental problem, only these two alternatives exist…We shall, in the following, use the term observation to refer to the sensory datum on which the decision is based. We assume that this observation may be represented as varying continuously along a single dimension…it may be helpful to think of the observation as…the number of impulses arriving at a given point in the cortex within a given time.” Also “We imagine the process of signal detection to be a choice between Gaussian variables….The particular decision that is made depends on whether or not the observation exceeds a criterion value….This description of the detection process is an almost direct translation of the theory of statistical decision.”
In what sense does the above framework relate to visual perception? I think we can easily show that, in concept and application, it is wholly incoherent and irrational.
I submit, first, that when I look around me, I don’t see any noise, I just see things. I’m also not conscious of looking for a signal to compare to noise; I just see whatever comes up. I don’t have a criterion for spotting what I don’t know will come up, and I don’t feel uncertain of - I certainly hardly ever have to guess at – what I’m seeing. The very effortlessness of perception is what made it so difficult to discern the fundamental theoretical problems. This is not, of course, to say that what the visual system does in constructing the visual percept from the retinal stimulation isn’t guesswork; but the actual process is light years more complex and subtle than a clumsy and artificial “signal detection” framework.
Given the psychological certainty of normal perceptual experience, it’s hard to see how to apply this SDT framework. The key seems to be to make conditions of observation so poor as to impede normal perception, making the observer so unsure of what they saw or didn’t see that they must be forced to choose a response, i.e. to guess. One way to degrade viewing conditions is to make the image of interest very low contrast, so that it is barely discernible; another way is to flash it for very brief intervals. Now, in these presentations, the observer presumably sees something; so these manipulations don’t necessarily produce an uncertain perceptual situation (though the brevity of the presentation may make the recollection of that impression mnemonically challenging). Where the uncertainty comes in is in the demand by investigators that observers decide whether the impression is consistent with a quick, degraded glimpse of a particular figure, in this case an RF of a certain type or a circle. I don’t see how one can defend the notion put forth by Swets et al (1961) that this decision, which is more a conscious, cognitive one than a spontaneous perceptual one, is based on a continuously varying criterion. The decision, for example, may be based on a glimpse of one diagnostic feature or another, or on where, by chance, the fovea happens to fall in the 180ms (Schmidtmann and Kingdom, 2017) or 167ms (Wilkerson et al, 1998) interval allowed. But the forced noisiness (due to the poor conditions), the Gaussian presumptions, the continuous variable assumption, and the binary forced choice outputs are needed for the SDT framework to be laid on top of the data.
For rest of comment (here limited by comment size limits), please see PubPeer.
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On 2017 May 06, Hilda Bastian commented:
The conclusion that implicit bias in physicians "does not appear to impact their clinical decision making" would be good news, but this systematic review does not support it. Coming to any conclusion at all on this question requires a strong body of high quality evidence, with representative samples across a wide range of representative populations, using real-life data not hypothetical situations. None of these conditions pertain here. I think the appropriate conclusion here is that we still do not know what role implicit racial bias, as measured by this test, has on people's health care.
The abstract reports that "The majority of studies used clinical vignettes to examine clinical decision making". In this instance, "majority" means "all but one" (8 out of 9). And the single exception has a serious limitation in that regard, according to Table 1: "pharmacy refills are only a proxy for decision to intensify treatment". The authors' conclusions are thus related, not to clinical decision making, but to hypothetical decision making.
Of the 9 studies, Table 1 reports that 4 had a low response rate (37% to 53%), and in 2 studies the response rate was unknown. As this is a critical point, and an adequate response rate was not defined in the report of this review, I looked at the 3 studies (albeit briefly). I could find no response rate in any of the 3. In 1 of these (Haider AH, 2014), 248 members of an organization responded. That organization currently reports having over 2,000 members (EAST, accessed 6 May 2017). (The authors report that only 2 of the studies had a sample size calculation.)
It would be helpful if the authors could provide the full scoring: given the limitations reported, it's hard to see how some of these studies scored so highly. This accepted manuscript version reports that the criteria themselves are available in a supplement, but that supplement was not included.
It would have been helpful if additional important methodological details of the included studies were reported. For example, 1 of the studies I looked at (Oliver MN, 2014) included an element of random allocation of race to patient photos in the vignettes: design elements such as this were not included in the data extraction reported here. Along with the use of a non-validated quality assessment method (9 of the 27 components of the instrument that was modified), these issues leave too many questions about the quality rating of included studies. Other elements missing from this systematic review (Shea BJ, 2007) are a listing of the excluded studies and assessing the risk of publication bias.
The search strategy appears to be incompletely reported: it ends with an empty bullet point, and none of the previous bullet points refer to implicit bias or the implicit association test.
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On 2017 May 22, Lydia Maniatis commented:
Part 1 This publication is burdened with an unproductive theoretical approach as well as methodological problems (including intractable sampling problems). Conclusions range from trivial to doubtful.
Contemporary vision science seems determined to take organization of the retinal stimulation out of the picture, and replace it with raw numbers, whether neural firing rates or statistics. This is a fundamental error. A statistical heuristic strategy doesn’t work in any discipline, including physics. For example, a histogram of the relative heights of all the point masses in a particular patch of the world wouldn’t tell anything about the mechanical properties of the objects in that scene, because it would not tell us about distribution and cohesiveness of masses. (Would it tell us anything of interest?)
In perception, it is more than well established that the appearance of any point in the visual field –with respect to lightness, color, shape, etc - is intimately dependent on the intensities/spectral compositions of the points in the surrounding (the entire) field (specifically their effects on the retina) and on the principles of organization that the visual process effectively applies to the stimulation. Thus, a compilation of, for example, the spectral statistics of Purves’ colored cube would not allow us either to explain or predict the appearance of colored illumination or transparent overlays. Or, rather, it wouldn’t allow us to predict these things unless we employed a very special sample of images, all of which produced such impressions of colored illumination. Then we might get a relatively weak correlation. This is because, within this sample, a preponderance of certain wavelengths would tend to correlate with e.g. a yellow, illumination impression, rather than being due, as might be true for the general case, to the presence of a number of unified apparently yellow and opaque surfaces. Thus, we see how improper sampling can allow us to make better (and, I would add, predictable) predictions without implying explanatory power. In perception, explanatory power strictly requires we take into account principles of organization.
In contrast, the authors here take the statistics route. They want to show, or rather, don’t completely fail to corroborate the observation that when surfaces are wet, their look colors are deeper and more vivid, and also to corroborate the fact that changes in perception are linked to changes in the retinal stimulation. Using a set of ready-made images (criteria for the selection of which are not provided), they apply to them a manipulation (among others) that has the general effect of increasing the saturation of the colors perceived. One way to ascertain whether this manipulation causes a surface to appear wet would be to simply ask observers to describe the surface, without any clues to what was expected. Would the surface be spontaneously be described as “wet” or “moist”? This would be the more challenging test, but is not the approach taken.
Instead, observers are first trained on images (examples of which are not provided - I have requested examples) that we are told appear very wet (and the dry versions), and include shape-based cues, such as drops of water or puddles. They are told to use these as a guide to what counts as very wet, or a rating of 5. They are then shown a series of images containing both original and manipulated images (with more saturated colors, but lacking any shape-based cues), and asked to rate wetness from 1 to 5.
The results are messy, with some transformed images getting higher ratings than the originals and others not, though on average they are more highly rated. But the ratings for all the images are relatively low; and we have to ask, how have the observers understood their task? Are they reporting an authentic perception of wetness or moistness, or do they believe are they trying to guess at how wet a surface actually is, based on a rule of thumb adopted during the training phase, in which, presumably, the wet images were also more color-saturated? (In other words, is the task authentically perceptual, or is it more cognitive guesswork?) What does it mean to rate the wetness of a surface at e.g. the “2” level?
The cost of ignoring the factor of shape/structure is evident in the authors’ attempt to explain why the ratings for all images were so low, reaching 4 in only one case. They explain that it may be because their manipulation didn’t include areas that looked like drops or puddles. Does this mean that the presence of drops or puddles actually changes the appearance of the surrounding areas, and/or that perhaps those very different training images included other organized features that were overlooked and that affected perception? Did the training teach observers to apply a cue in practice that by itself produces somewhat different perceptual outcomes? I suppose we could ask the observers about their strategy, but this would muddy the facade of quantitative purity.
At any rate, the manipulation (like most ad hoc assumptions) fails as a tool for prediction, leading the authors to acknowledge that “The image transformation greatly increased the wetness rating for some images but not for others…” (Again, it isn’t clear that “wetness rating” correlates with an authentically perceptual scale). Thus, relative success or failure of the transformation is image-specific, and thus sample-specific; some samples and sample sets would very likely not reach statistical significance. Thus the decision to investigate further (Experiment 1b) using (if I’m reading this correctly) only a single custom-made image that was not part of the original set (on what basis was this chosen?) seems unwise. (This might seem to worsen the sampling problem, but the problem is intractable anyway. As there is no possible sample that would allow the researchers to generate reliable statistics-based predictions for the individual case, any generalization would be instantly falsifiable, and thus lack explanatory power).
The degree to which any conclusions are tied to the specific (and unrationalized) sample is illustrated by the fact that the technical manipulations were tailored to it (from Experiment 1a): “In deciding [the] parameters of the WET transformation, we preliminarily explored a range of parameters and chose ones that did not disturb the apparent naturalness of all the images used in Experiment 1a.” Note the lack of objective criteria for “naturalness.”). (We’re not told on what basis the parameters in Experiment 1b were chosen). In short, I don’t think this numbers game can tell us anything more from a theoretical point of view than casual observation and e.g., trial and error by artists, already have.
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On 2017 Jun 21, Lydia Maniatis commented:
(Comment #2)
The three sentences of the conclusion (which I annotate below, in its entirety, reflects the article's utter lack of content:
- *"Motion information generated by moving specularities across a surface is used by human observers when judging the bumpiness of 3D shapes." *
The boundaries of specularities are effectively contour lines. It would be thoroughly unrealistic to predict that they would not play a role, moving or not. And the observation had already been made.
- "In the presence of specular motion, observers tend to not rely on the motion parallax information generated by the matte-textured reflectance component."
The two parts of this sentence seem to be a non-sequitur - how could observers of specular motion employ information generated by matte-textured objects (i.e. objects other than the ones they were observing)? What the authors mean to say is that observers don't use the motion parallax info generated by the specular stimulus. While they frame this as though it were an actual finding, it is, as discussed above, a purely speculative attempt to explain the poorer performance with specular objects.
- *"This study further highlights how 3D shape, surface material, and object motion interact in dynamic scenes." *
It really doesn't, given the mixed results and failed predictions. It couldn't for a number of other reasons, discussed below.
All of the heavy lifting in this article is done by computer programmers, whose renderings are supposed to qualify as "specular" "specular motion" "matte-textured" etc. These renderings rest on theoretical assumptions most of which are never made explicit. They are, however, inadequate; we learn that observers sometimes saw the moving specular stimuli as non-rigid. This is a problem. There is no objective description of the phenomenon "specular object in motion around an axis" other than "objects generated by this particular program." Is there any doubt that results would have been different if the renderings had accurately mimicked the physical phenomenon? If the surface of the object is seen as changing, don't this affect the "motion parallax" hypothesis? The speed with which a particular point on a surface is moving optically is confounded with the speed with which it is moving on its own.
The so-called matte-textured objects appeared purely reflective when not in motion. The apparent specularities were "stuck-on" so that they moved with the surface. I have never seen a matte surface with this characteristic. I would be curious to see the in-motion renderings, because I cannot imagine what they look like. What is clear is that a simple reference to matte textured objects is not appropriate. We are talking about a different phenomenon, which may not correspond to any physically actualizable one. This latter fact wouldn't matter if the theoretical framework were tight enough that such stimuli allowed isolation of some particular factor of interest. Here, however, it is just means that "matte" doesn't mean what it normally is thought to mean.
Observers were confused about the meaning of the term "bumpiness." Stimuli involve hills and ridges of various extents as well as varying apparent heights. The authors were interested in height. They instructed observers who asked for clarification (not the others) that they were interested in "the amplitude not the frequency." I would say a large hill or a wide ridge could qualify as more ample for people not thinking in terms of graphs with height in the ordinate. In other words, I think there is a observational confound between extent and height of the bumps.
In the introduction, the authors refer to previous papers which came to opposite conclusions. Presumably, this means that some relevant factors/confounds were not considered. But the authors don't attempt to analyze these conflicted citations, which thus merely function as window-dressing. They move on to their experiments, on the slightest and vaguest of pretexts, with poorly described stimuli and poorly controlled tasks.
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On 2017 Aug 25, Jason R Richardson commented:
Drs. Blakely and Melikian, thank you both for your insightful comments. In working with these cells over a number of years, we have found that while the cell line expresses all of the necessary components to be identified as dopaminergic, it neither synthesizes a significant amount of dopamine nor has functional dopamine uptake. This is likely because of the diffuse nature of the protein expression identified by Dr. Melikian, which may be because it was generated by immortalizing cells from embryonic day 12 rat. I believe when I was a postdoc, I did some co-labeling and observed that the DAT was primarily present in the ER and golgi in these cells, suggesting that the intracellular machinery may not be mature enough to fully generate a functional and fully glycosylated DAT. I should note that the original group that made the N27 line recently re-cloned it and purified cells from this new clone had higher expression levels of both TH and DAT (Gao et al., 2016). Although, there were no functional studies for DAT-mediated uptake with the re-cloned line, they did show a modest increase in susceptibility to 6-OHDA and MPP+. Our primary goal for this paper was to better characterize the role of histone acetylation and transcription factor binding in the epigenetic regulation of DAT expression based on our previous studies in SK-N-AS cells (Green et al., 2015) in a rat cell line that we could then translate to in vivo studies. I certainly agree that additional studies in cells that display a more mature phenotype that allow for determination of function are warranted. I think both comments bring out a very important point regarding the study of transporter regulation. That is, cell context and system are critical to the interpretation and translation of mechanisms regulating the DAT to in vivo systems.
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On 2017 Oct 19, Polina Vishnyakova commented:
Dear colleagues, in order to maintain a healthy scientific debate we need to clarify the statement, which you provided in Discussion of this paper. You wrote: «These findings are inconsistent with the findings of Vishnyakova et al. who reported that OPA1 was upregulated in PE placentas. […] The findings of Vishnyakova et al. were mainly based on gene expression. Levels of DNA or RNA may be unable to predict protein levels accurately, as they do not account for post-transcriptional/translational modifications». It is important to note than in our work we observed changes both on mRNA and protein content level of OPA1 and these findings surely disagree with your data. But we think that this could be explained by the difference in patients characteristic: we divided patients with preeclampsia basing on gestational age while you included women only with severe preeclampsia. Plus in current paper you analyzed only OPA1-L form, but not both forms (full OPA1-L and cleaved OPA1-S). So obtained difference in our findings could be explained with these points. Best regards.
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inst-fs-pdx-prod.inscloudgate.net inst-fs-pdx-prod.inscloudgate.net
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Summary Marquit begins by introducing us to the principal concern of philosophy of technology, which is how technological development influences societal organization and culture and how culture and society influence and drive technology. He then repeats the three theories of technological and societal relationships that Nye introduced us to last week. Technological determinism states that technology spontaneously evolves and that society must adapt to make efficient use of it. Second, technological advance is driven by human culture and cultural developments. Third, a mix of both of those views is the most generally held. Marquit makes the case that Human evolution is intertwined with technology and that technological, biological and societal interactions make up a kind of pyramid of forces that created the modern Human. Bipedality freed up our hands to use and create tools, while the need and ability to use tools may have driven us to develop brains large and capable enough to make use of the tools. Changes in the hand allowed for the use of tools, while the lowering of the larynx and decrease in canine teeth size enabled articulate speech which was another use of larger brains. Tools, intelligence and bipedality were critical in the move to humans as hunters. The first evidence of human hunting is from one-hundred-thousand years ago, an eight foot wooden spear found in an elephant. As a case-study for ancient hunting societies the Mbuti people of the Ituri rain forest in Zaire are a good example. Most of the people in the society participate in the hunt, and there is little hierarchical structure. There is much cooperation between ages and genders, especially in the important songs used for various reasons. Group members make decisions collectively, with the chief providing guidance in conflict, the shaman providing religious guidance, and singers and dancers serving important roles as well. The first major revolution in social organization associated with technological developments was in 10,000 B.C. with the advent of the city-state in Mesopotamia, Egypt, China, India, Mesoamerica, and the Andes. The first sign of technological change involved the transition to complex foraging, society becoming more static with the ability to acquire a surplus of resources and store them. This gave rise to larger populations and allowed for some specialization. Social differentiation arises through the need for individuals to be in charge of administrative tasks. Structures are built to house goods and ceremonial structures hint at the possibility that leaders and central management were present. Eventually the state emerges as a bureaucratic institution and exerts control over resources. Needing a reason to justify this control, institutions are put in place based on morality and being enforced with the threat of physical violence. In 3300 B.C. bronze metallurgy is introduced in Mesopotamia and Egypt. The ability to create metal tools significantly increases productivity and harvest capability, leading to a surge in population and allowing for more specialized professions, including the first known specialization that is not related to the ruling bureaucracy or directly to food production, the blacksmith. Urban developments spring up as a result of these changes and society becomes stratified into state societies by the 4th century B.C. which are ruled by priest-kings. Later in the Middle East accounting for all the surplus supplies becomes critical and because of this need, mathematics, the first currency and the first written language, cuneiform is developed. Greeks as discussed in the last article, equated technology and physical labor as being lesser than theorizing about philosophy of mathematics. The Greeks also have slaves, so labor is much more efficient than implementing new technology. The Romans a few centuries later did innovate and had a much higher opinion of technology. They used their centralized power to build aqueducts, roads and grain mills. The Chinese in Asia, valued technology, science and writing very highly. As a result were much ahead of their western peers for a long time. The early move to a feudal system of a lord, taxation in the form of unpaid labor, and very centralized government however, stunted their growth, there was not enough free time available to the lower class and the middle class was caught up in serving the lords who were content with the system.
Response Marquit lays out the principal concern of philosophy of technology which is how technological development influences societal organization and culture and how culture and society influence and drive technology and I think this is the lens through which we should be looking at this article. The course dictates that we look at how this frames our relationship to technology which I think is complementary. Regarding the triangle or pyramid of society, biology and technology, I find this very relevant in today’s world. Soon technology and society may even more directly impact our biology. Indirectly our biology has been greatly shaped in recent years by modern medicine. In times past many of us with what are seen as minor health issues today would be dead or looked upon as detrimental to society, today many of these health issues are able to be corrected. In the near future the relationship with biology and technology/society will have a much more direct impact. As long as society allows, humans will begin augmenting themselves, if not at a dna level perhaps as implants, and it will be something to keep an eye on. I found the portion of the article relating to the formation of city-states and production and storage of excess products extremely interesting and important. The relationship between technology and society is really boiled down and almost purified in this moment. Society was so simple before we had excess food, there was little to no hierarchy and no social classes. We see a clear delineation between the time before and after humans started to settle down. The creation of modern society is seen in its’ infancy in this period and I think it can be a great place for me to study technology going forward. It surprised me how much studying history really taught me about how technology affects us today! I am happy that we will be studying more about Greek and Chinese society after this paper, because it seems brushed over compared with how much detail and growth we really see in the ancient Mesopotamian and Egyptian cultures within the article. I did find it interesting how these more modern (by comparison) groups were described as failures in Marquit’s opinion. The Greeks held themselves back by thinking of technology as a lesser endeavor, while the Chinese organized their society in such a way that they did not allow for growth, the lavish lifestyle of the upper class cramped the growth of their area.
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Here is Paula Freebird's Summary and Response to David Nye's essay, "Can we Define Technology"
. . .
Paula Freebird “Can We Define Technology?” by David Nye February 4, 2018
Summary
For this week's summary and response I have chosen to write about three themes in David Nye's essay: 1) tools and stories/language, 2) evolution of the word "technology'', and 3) technology and gender. Ney develops a unique theory about technology when he discusses how stories are almost "built in" tools. What does he mean by that? First, he compares the structure of stories — a situation, an encountered problem, a solution — to the structure in the invention of a tool. Whether by accident, or through planning, a tool comes into being when a problem is recognized within a situation, the solution is visualized, and then the tool is used. For Nye, thought process we go through when we invent, encounter, or use a tool involves the same thought process we go when we create stories. However, even if the structures are that same, Nye does not want us to think that we 'read" stories and tools in the same way. When we 'read' a tool we are in it and with it, using it in a practical way. Textual stories, on the other hand, are abstract, removed, and theoretical.
The evolution of the word "technology'', according to Nye, begins with the Greek word "techne". While the Greeks did not appreciate the manual work implied in the activity of "techne" (in other words, using tools for work) they nevertheless had a word for activity itself. The word seems to have disappeared for many centuries after the Greeks and only appears in the early 1800s (in the very early Industrial period) to refer, much like the Greeks, to specific skills (like "glassmaking" etc.) — or even more specifically to books (—logy) written about specific arts. In other words, the "technology of glassmaking" would refer to a book written about glassmaking.) As the Industrial period develops, Nye goes on to say, the word "only gradually came into circulation to the point where in the nineteenth century, institutions (like the Massachusetts institute of Technology) began to adopt the term. Broader use of the terms technologie and iechnikl in Germany led to their translation into the English technics in the twentieth century. Technology then becomes part of the professional definition of engineers. In a digression of the definition of the term, Lewis Mumford used the terms eotechnic, paleotechnic, and neotechnic to describe a chronology of technological development. While these terms are not used anymore, the word technology goes through several transformations in the twentieth century leading Nye to complain that "the meaning of "technology" remained unstable in the second half of the twentieth century, when it evolved into an annoyingly vague abstraction." Nye finally concludes that the word has finally stabilized to become "a comprehensive term for complex systems of machines and techniques."
Nye only touches on the relationship between technology and gender towards the end of the essay. He acknowledges that, while Mumford contributed a lot to our thinking about technology, he (and presumably all other thinkers about technology at that time) "missed ... how thoroughly "technology" was shaped by gender." Nye backtracks to the medieval era to point out how deeply women were involved with trade and gives us examples, such as the making of ale, as being thoroughly controlled by women. It is only in the modern period that our perception of technology changes. Nye cites Ruth Oldenziel argument that Western society only relatively recently defined the word "technology" as masculine."
Response
Since the guiding question of this course is: “How does awareness of the history and philosophy of technology frame our relationship to technology?" I will focus my response to answering this question in relation to how I see my own thinking changing. It's only the beginning of the course, and this is only the first essay; still, i think the changing of my thinking might have already begun.
Regarding tools and stories, I am not sure whether I believe it or not. It seems to me to be a hit far¬fetched. I think Nye wants to somehow connect “language" with "tool making" — perhaps because he wants to show both as being deeply human traits. But I can't see any "story" in a tool. Even at the end of his argument, he says we don't read textual stories and tools in the same way. Of course. That's exactly what I mean. Maybe I can say I "use" stories (like to put my kids to sleep) the way I "use' a tool. Still, it is curious to me that this kind of far-fetched thinking can come up in the course of discussing technology. In that sense, my thinking about how technology “frames[s] our}my] relationship to technology" is being affected. While I do not have to accept everything I read, I have to think about it and try to say as clearly as I can "why” I do not accept it.
The historical evolution of the word "technology" brings to my mind a connection between "practice" and "theory". Practice is, well, practical. I don't need to know the name of the tool I am using to be able to use it. So, the fact that people (except for the Greeks who were —there is no other way, to say it — lazy because they had slaves) would not care about coming up with word like techne does not surprise me. They were busy using the tools. This makes me think the modern return to developing the word (technologie, technik, technique, technology, tech, etc.) may be part of a theorizing process we are in (lazy like the Greeks, I don't know...). Anyway, this relationship between practice and theory is probably a very important thing for me to think about in relation to my relationship to technology.
The topic of gender and technology, however, is really changing the way I think about technology. I don't have much to say about it right now (Nye does not give us much). But, hard as it may seem to believe, it seems to me to be critical to our understanding of technology. I’ll say this, until we figure out this relationship, we may never be able to get out of the technological quagmire we find ourselves in. There, I said it. It's a stab in the dark, but I think I will have more to say on this as I continue reading.
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aslearningdesign.net aslearningdesign.net
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William Buckland
Nye, D.E. Technology matters: Questions to live with
02/04/2018
Summary
Nye’s Chapter 1 “Can we Define Technology?” has many interesting themes relating to technology. He begins this chapter with a theme of technology and human/animal evolution. Nye points out that for a time, it was thought only humans used tools, even until Benjamin Franklin’s time. Well, it was actually Benjamin Franklin who came up with the idea that tool-making is what makes humans different from animals. Only more recent studies have shown animals, such as a chimpanzee, using tools… Not sure what the .... is for AND doing so with foresight. The article makes a point to describe in detail specific traits of humans which have evolved. It discusses the opposition between thumb and finger, the enlarging of the human cortex, and humans' adaptability. Furthermore, he contrasts animal and human relationships to technology for further illumination: “’animals are atechnical; they are content with the simple act of living.’ Humans, in contrast, continually redefine their necessities to include more.”Nye goes on to make the point about tools being inseparable from human evolution. He suggests that this means tools are more than simple objects, rather they express larger sequences of actions and ideas. Nye insinuates the mind plays an important role, and that an imagination of altered circumstances, or how present circumstances may be made different, are necessary for tool creation. These paragraphs can actually go together. They are a bit too short on their own.
Deeper in the chapter, a new theme emerges about technology and science: the "fundamental misconception." Nye begins this theme by describing a bookstore, and where one may find books related to technology. They would not be found in their own section, rather mixed in many sections throughout. again, your paragraphs are too shortNye states that the commonly held misconception is discoveries emerge from “pure science,” and that technology is simply the solution through scientific principles. Throughout history, technology has come first, and then the science to explain how it works followed. Even more oddly, technology can arise before there was ever a need for it! What does this mean?
Nye also points out people’s general misconception of what to call technology. Cyril Stanley Smith believes it should be called an art. Most people believe it is an applied science, supposedly word choice falsely. Smith makes the point that while technology in modern times is more of an applied science, it was an art form throughout much of history, longer than it has been an applied science.
Nye’s last theme in the end of the chapter is technology and culture: “technological determinism.” As previously mentioned, Nye made a point about technology being inseparable from human evolution. Technology was a major factor in societal evolution. “Learning to use tools was a crucial step… because it led to a more complex social life.”The article points out that tools predate written language. Nye suggests that telling stories and using tools are similar, and both contribute to social development. Humans are determined to have more and do more, and tools are the method. This is an example of “technological determinism,” defined as a reductionist theory that assumes that a society's technology determines the development of its social structure and cultural values.
Nye’s use of imagery to define “technological determinism” is quite good. The article describes a scene from Kubrick’s 2001 where an ancestor of modern man picks up a bone, uses it as a weapon, then throws it into the air where it turns into a space station. Kubrick is implying that technology is determined; there has been a continuous development from pre-stone age to present times. Nye closes by posing a question: “Should we accept such determinism?”
Response
Looking at Nye’s theme on technology and evolution, I understood all of it, and was not challenged in my comprehension. For the most part, it resonated with everything I have known and believed, short of learning some new facts and ideas. I did not know it was believed only humans used tools, and the idea of tools expressing a sequence of actions was something I did not ponder before. This theme has affected my relationship to technology in the sense that I realize the profound impact it had on our own evolution. If tools were never used, or hardly used, we may still resemble our prehistoric ancestors. I also saw how “known” truths or facts can evolve or change over time, just as humans and technology.
The next theme was slightly more challenging. I suppose that is normal given the theme is technology and science: the “fundamental misconception.” I have always thought of technology as an applied science, so it was a new idea for me to think of technology as an art. I also never thought about the labels of technology, or how researching it may be problematic since it is mixed into many sections of a library and has been called many names. As you pointed out, I failed to relate the bookstore layout to show that we don’t treat technology in its own right. That was my understanding, but I did not accurately portray this. This theme certainly raised my awareness and relationship to technology by making me realize that it will be challenging to research it, and how it is vastly different now than it has been over the course of history. It also made me think that perhaps the order in which technology arises, i.e. technology, need, scientific explanation, is not important. It seems to go in any order throughout history. More recent times would certainly suggest the order proceeds in the opposite direction than is written above. Very good thinking here.
The last theme discussed, technology and culture: “ technological determinism” was very interesting to learn about. I wouldn’t say it was challenging, as much as it was a learning of new ideas and insights about technology. I definitely accept what I learned, and it resonates with my general previously held knowledge. I had a profound philosophical thought, relating to tools predating written language. Tools were needed to write language, so it could be said that tools are the cultivating factor of human culture and society. Without tools, there is no written communication to be shared, bringing the world’s knowledge together. though, if you consider writing as a tool in itself, then it's just a matter of one tool being used to create another Man will never stop needing, wanting, inventing, creating, all at an astronomical rate that accelerates over time. It is an exciting time to be alive surrounded by so much technology, but at the same time, at which point do the risks outweigh the benefits? This is similar to Nye’s closing question, and a moral dilemma for many who think about “technological determinism.” This has impacted my relationship personally to technology, in that I can imagine technology as its own being, “determined” to grow of its own accord in a sense.
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en.wikisource.org en.wikisource.org
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they may intoxicate themselves on literature as on pure water, and as cheaply, too, for there will then be fountains of literature in the streets as there are now hydrants.
Using the word "cheaply" made me think of how easily and cheaply we can order books on amazon or the like. I recently got 5 used novels online for about $30.
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doc-08-5g-docs.googleusercontent.com doc-08-5g-docs.googleusercontent.com
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2
Discussion Questions for Chapter 4: Collective Unconscious: The Demise of Radical Feminist Publishing
“There is a risk that the absorption of lesbian literature into the lists of mainstream houses may not be paralleled by a similarly rapid elevation of lesbian employees into the managerial structures of such firms – resulting in a tokenising discrepancy between cultural profile and political power of the kind that bedevils black women’s writing” (pg. 162)
Q1: Do you think antiracist and feminist work in publishing are synonymous? The black women felt obliged to work with the feminist presses since the press was the only advocate for lesbian rights. At the sacrifice of their own personal racial identity, is standing up for another cause such as feminism applicable? Do you think the model of the collective press is the reason why the black women faced racism?
“A third obvious source of finance for radical women’s presses (obvious, at least, in the 1970s) was public arts funding in the form of local government grants – a source of start-up capital upon which alternative feminist publishing initiatives relied heavily. Two problems arose from these presses’ public funds dependency: firstly, a tendency to regard this income as speciously ‘non-political’” (pg. 156)
Q2: The government has a federal and provincial budget that prioritizes funding for all people no matter sexes. The feminist press is a political movement in which the presses argue the need to stray away from capitalism. However, governments are built on the sole merit of capitalism. Should democratic governments fund political projects such as the feminist press? Would funding such projects indicate government support? How do we separate the social causes from any political agendas?
"But the imperatives of a heterosexual-dominated industry required that lesbianism be portrayed as a tortured, unfulfillable condition, hence the preponderance of the ‘dilettante-dyke-returns-to-her-husband’ plot and the ubiquity of the suicidal lesbian protagonist – a direct descendent of The Well of Loneliness model of the 1920s (Koski and Tilchen, 1975: 42; Adams, 1992). Because of this experience of image distortion and literary ventriloquism, lesbian presses of the 1970s were commonly at the vanguard of the separatist media movement, asserting that the goal of developing ‘political analysis unhindered by patriarchal values’ required the establishment of ‘our own culture’" (pg. 159)
Q3: The article argues that the feminist press needs to function outside of the heterosexual male dominated printing presses culture. Do you agree that the feminist press should be separate from traditional presses or do you think that feminism presses should function within the traditional publishing model? Do you think that creating "our own culture" outside of popular culture is an effective method of publishing material? What are some key issues of creating a separate culture from the norm?
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spring2018.robinwharton.net spring2018.robinwharton.net
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Michael Baxandall has noted: "We do not explain pictures: we explain remarks about pictures-or rather, we explain pictures only in so far as we have considered them under some verbal description or specifi-cation ... Every evolved explanation of a picture includes or implies an elaborate description of that picture. "4
Baxandall makes a good point about pictures and how we use language to truly understand what one is looking at. In the context of objects in general, I think the supplementary text "3-D print your way to freedom and prosperity" sheds some light on how that could change if 3-D printing becomes more commonplace. I think being able to print whatever simple product one needs can change perceptions in a material culture and make certain things lose the value they may have once had.
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press.rebus.community press.rebus.community
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The Domains initiative enables student to build the contemporary version of what Virginia Woolf in 1929 famously demanded in A Room of One’s Own – the necessity of a personal place to write
I’ve read many excerpts from Woolf’s writing online and its some of my favorite. I agree entirely that everyone needs a personal space to write and do their best thinking. I think it’s interesting that Watters seems to use a personal space on the internet as a tool we can use in place of a physical space to write, which we may not always have, to increase our intellectual development.
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inscription.commons.gc.cuny.edu inscription.commons.gc.cuny.edu
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That gave rise to certain technical difficulties with fastening the needles securely, but after several attempts we were successful. We didn’t spare any efforts. And now, as the inscription is made on the body, everyone can see through the glass. Don’t you want to come closer and see the needles for yourself.”
Hmmm. I think the Officer is wildly self-conscious and nervous about the Traveler's understanding and opinion on the apparatus, and on the execution. With that said, I think glass may make the apparatus more aesthetically pleasing to the audience. Perhaps having glass rip into a body is more appealing to the eye than just needles? The glass may also show the worth of the apparatus...
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- Jan 2018
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spring2018.robinwharton.net spring2018.robinwharton.net
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American Artifacts
"3-D print your way to freedom and prosperity" by Jathan Sadowski
"The maker movement embraces a kind of naively apolitical, techno-economic, capitalist utopia that thrives on individualistic value" (Sadowski). This quote has it's own section in this article and provides a strong mantra for the phenomenon that is 3-D printing. Jathan Sadowski, a Ph.D. student at Arizona State University, talks about the concept of 3-D printing and how versatile it can be. The article begins with comments made by Barack Obama a State of the Union address from 2013. "'Three-D printing [has] the potential to revolutionize the way we make almost everything,' he said." Sadowski agrees with this and brings up a lot of points about the benefits of 3-D printing, such as the ability to be creative, ease of accessibility, and individualism and power given to the entrepreneurial mind. However, Sawoski argues that these very benefits fit well into "the Californian Ideology". This theory suggests that high-tech entrepreneurs can bypass the regulations and systems that have been established. However, these systems would not be broken or disrupted, but would actually stay the same. Sadowski makes another strong point about what dangers could be presented in easily-accessible 3-D printing. Since manufacturing regulations can be so easily disregarded when 3-D printing, dangerous products can be made. Sadowski writes about Cody Wilson, "a founder of Defense Distributed, [who] designed, prototyped, and posted plans for a working 3-D-printed plastic handgun he called the Liberator."
This article was written in 2014, when 3-D printing was still a very new concept and the potential for what could be created and which huge conglomerates could be toppled where boundless. However, the years have past and 3-D printing has slowly crept away from the mainstream media and dinner table conversations. The equipment needed to 3-D print a few years ago was still not consumer-friendly, but now you can buy 3-D printers for a few hundred dollars. Many schools around the United States have 3-D printers that are accessible to schools. I believe that the 3-D printing concept was always destined for small-scale usage. The flexibility to create whatever someone needs works best in a small-scale, because these products being printed do not have to go through the quality control that bigger manufacturers. I think the Californian Ideology did eventually come true, but under a different pretense. I think that the "system" was not impacted by 3-D printing because the bigger financial piece of the pie is the manufacturing of the 3-D printers, not so much the products being printed.
Source: Sadowski, Jathan. "3-D print your way to freedom and prosperity." Al Jazeera, 17 May 2014, http://america.aljazeera.com/opinions/2014/5/3d-printing-politics.html.
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inst-fs-pdx-prod.inscloudgate.net inst-fs-pdx-prod.inscloudgate.net
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Apart from structural changes favoring bipedal locomotion, the fossil trail from the australopithecines to Homo sapiensis marked by significant increases in brain size (Falk, 1993, p. 64); changes in the bone structure of the hand (Napier, 1993); a lowering of the larynx so as to increase the space between the larynx and the back of the nasal cavity, thereby enhancing the possibility for articulate speech (Laitman, 1993); and a decrease in the size of the canine teeth (Skelton et al., 1993).
The biological components that may have led to tool making may be questionable. Still, there is evidence to back it up. Can you think of any aspect of technology use today that is tied to biological development -- for example, diseases that we are more prone to contract because of our technology? Any others?
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spring2018.robinwharton.net spring2018.robinwharton.net
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The designs are not only aesthetically pleasing but also deeply culturally significant. The artistic renderings displayed on the basket are representations of both rhe abundant natural landscape and the Mohegan cosmology. As the Mohegan elder Gladys Tantaquidgeon explains, "To the Mohegan, designs and life are more than simple representations of narure.
The symbols an designs on the baskets represent natural landscape and Mohegan Cosmology. Gladys Tantaquidgeon was a Mohegan medicine woman, anthropologist, author, and tribal council member. She said "to the Mohegan, designs and life are more than simple representations of nature. There is a spiritual force that flows through all things, and if these symbols are true representations of that force, this spirit should be expressed in these designs." To many these designs may not look attractive and if we do not Mohegan cosmology than we have no chance at understanding what they mean. However these baskets have a large power in them to the Mohegan culture. This compares easily with "The Life of an Object ". These baskets do more than just symbolized something. In the Digital Curation project, the student is forced to think of what the object does, rather than what it symbolizes because that would leave the value of it completely up to the viewer. These Mohegan baskets are more than a representation of the culture, they are a part of it.
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marginalsyllab.us marginalsyllab.us
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Otherwise, changes in the school institution and tradition will be looked at as the arbitrary inventions of particular teachers; at the worst transitory fads, and at the best merely improvements in certain details—and this is the plane upon which it is too customary to consider school changes.
I think this quote serves as counterpoint to the Connected Learning and Research Agenda quote on Page 14 (Connected learning recognizes a tension... ... competition for scarce opportunities.) The tension that the Agenda describes is an incomplete implementation of connected learning that some may consider as a fad in the eyes of Dewey. Again, to make sure that the Agenda policy makers can implement the alternative connected learning pathways, policymakers must take on Dewey's broader social view that we must undertake the learning paradigms that enhance student learning...
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slack.com slack.com
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Customer isn’t the only one with responsibilities; we have some, too. We will (a) make the Services available to Customer and its Authorized Users as described in the Contract; and (b) not use or process Customer Data for any purpose without Customer’s prior written instructions; provided, however, that “prior written instructions” will be deemed to include use of the Services by Authorized Users and any processing related to such use or otherwise necessary for the performance of the Contract. Be assured that (a) the Services will perform materially in accordance with our then-current Help Center pages; and (b) subject to the “ Non-Slack Products” and “Downgrade for Non-Payment” sections , we will not materially decrease the functionality of a Service during a subscription term. For any breach of a warranty in this section, Customer’s exclusive remedies are those described in the sections titled “Termination for Cause” and “Effect of Termination”. Keeping the Services Available As further described in our Help Center pages, for some of our Services, we also offer specific uptime commitments paired with credits, if we fall short. In those cases, the credits will serve as what the lawyers call liquidated damages and will be Customer’s sole remedy for the downtime and related inconvenience. For all Service plans, we will use commercially reasonable efforts to make the Services available 24 hours a day, 7 days a week, excluding planned downtime. We expect planned downtime to be infrequent but will endeavor to provide Customer with advance notice (e.g., through the Services), if we think it may exceed five (5) continuous minutes. Protecting Customer Data The protection of Customer Data is a top priority for us so we will maintain administrative, physical, and technical safeguards at a level not materially less protective than as described in our Security Practices page. Those safeguards will include measures for preventing unauthorized access, use, modification, deletion and disclosure of Customer Data by our personnel. Before sharing Customer Data with any of our third party service providers, we will ensure that the third party maintains, at a minimum, reasonable data practices for maintaining the confidentiality and security of Customer Data and preventing unauthorized access. Customer (not us) bears sole responsibility for adequate security, protection and backup of Customer Data when in Customer’s or its representatives’ or agents’ possession or control or when Customer chooses to use unencrypted gateways (e.g., IRC/XMPP clients) to connect to the Services. We are not responsible for what Customer’s Authorized Users or Non-Slack Products do with Customer Data. That is Customer’s responsibility. The Slack Extended Family We may leverage our employees, those of our corporate affiliates and third party contractors (the “Slack Extended Family”) in exercising our rights and performing our obligations under the Contract. We will be responsible for the Slack Extended Family’s compliance with our obligations under the Contract.
Nice to see that they acknowledge that they also have terms as well as the customers.
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inst-fs-iad-prod.inscloudgate.net inst-fs-iad-prod.inscloudgate.net
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Cultural differences can arise with partnering institutions, as well as across national and international communities of participants.
We must also think of the different power scales that may be involved in cross-cultural partnerships and how that may affect the weight of partner influence even within a seemingly "level" digital arena.
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doc-0g-5g-docs.googleusercontent.com doc-0g-5g-docs.googleusercontent.com
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Jean Watts and the Spanish Civil War: Writing, Politics,and ContextsA Case Study Collection
Seminar Leadership Discussion Questions:
1) “If we are to understand how the dynamics of gender shaped the experiences of women in the Spanish Civil War, whether as journalists, nurses, or combatants, we must also account for the ways that narratives about their exceptionality, their sexuality, and their femininity continue to resonate through the voices of their contemporaries.” (p. 5, in conclusion)
How are particular narratives about women and their “exceptionality, their sexuality, and their femininity” being perpetuated today? What is the effect of a campaign like #metoo on women’s work and personal reputations? (Do you think there exists a darker side besides the empowerment this campaign offers?)
2) “…. despite the fact that they were perfectly qualified for the work at hand, their qualifications may not have overridden their gender. Watts and Gellhorn may have been justified in assuming that their previous experience was largely irrelevant, even as they narrativized their experiences years later.” (p. 16-17, in case study four)
Where do we see this happening today? What industries do women need to fight harder to get into? What about environments where men need to fight more to get into/break stereotypes about (e.g. male nurse practitioners)?
3) Watts and Gellhorn had a tendency to use varying pronouns and points-of-view, and to shift focalizations during their articles. Watts often inserted herself into articles, considering herself part of the Spanish community and not withholding her anger and sorrow about what she saw around her. Gellhorn invited readers to imagine themselves in the situation, cultivating an intense emotional impact on readers. (see p. 18-28, in case study four)
Do you think that journalists have this kind of distinct voice today? Is it more present in certain areas of the industry than others (i.e. war reporting today)? Has it been overridden by the market-orientation – or ‘hamsterization’ – of the journalism industry?
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