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.

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.

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."

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.

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.

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.)

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.

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^-1.6 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.

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.

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.

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

On 2017 Jul 03, P Jesper Sjöström commented:

Thanks for your interest in our work. I would like to make the following points:

1. 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.

2. 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.

3. 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.

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.

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.

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.

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).

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).

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.

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).

1. 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.

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.

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.

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".

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.

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.

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

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?

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.

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.)

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.

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.

1. How did we jump from “shape perception” to “RF detection against a circle”? How is the latter related to the former?

2. 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?

3. 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.

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.

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.

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:

1. *"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.

1. "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.

1. *"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.

1. 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.

2. 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.

3. 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.

4. 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.

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.

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.

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.

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.

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 short

Nye 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.

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.

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?

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.

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.

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...

"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.

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?

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.

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...

Nice to see that they acknowledge that they also have terms as well as the customers.

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.

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?

Can someone give the dates for each of the names referenced in this paragraph? I think Nye jumps around a lot and it would be good to track what he's saying by looking at the dates. (It's a good idea to give dates for any names or events that you see in this article -- if someone has not done so already.)

This particularly resonates with me. I have 3 children and I think about how differently I look at and handle things with my 3rd child versus my first child. I think this is something as educators we need to keep in mind when working with our families.

I think this is one of the most important underlying ideas behind the entire Domain of One's Own project - it gives students that may otherwise lack power, control, or autonomy command over their identity and information.

Look at the changes Lincoln made from this sentence to the 'final draft' above. What is one way you think he improved the text?

The fish is fish illustration made me think about how it may be easy to assume students see things the way we do because we may not be aware of what preexisting views they hold. I think it would be important as a teacher to not let students' misguided views surprise you but to spend more energy helping them understand the information.

I want to annotate!!!

Overall, I like this study and can understand why it was published. This is clearly an area that needs further research. Also, very progressive to only post the effect sizes, interesting. This study is a positive step in the right direction, and provides evidence that we are in need of programs that incorporate sibling-focused strategies implemented into the community. I think this program has the opportunity to promote positive sibling interactions, as this tends to be an area that is quite overlooked. It was always just assumed that you will figure out a way to get along with your siblings,and from that - you will learn pro-social behaviors. I like how this study incorporated the parents, i think that is very effective. However, what about extended family members or grandparents? What if the child was not raised by their parents? I think that future research may want to look at adding another group, in order to strengthen the research. Specifically, how can we determine that it was the siblings are special program that changed the behaviors, and not just interacting in an activity? What if they instead had: Experimental group (SAS program), control group (who did nothing different) and a third group that did some kind of arbitrary activity. Only then can we determine that it was in fact the SAS program that changed the behavior and not just participating in an activity?

Yes, pretty much every knowledge and skill I can think of can be broken down into smaller and smaller components. There is no single correct organization for learning outcomes as long as the system is something the human brain will handle and the amount of content is reasonable for the course timeframe. (e.g. 7 plus or minus 2 is generally something easily remembered)

Many disciplines have outcome hierarchies organized from broad (high-level) to specific as we move from institution to department to course to lesson. However, some disciplines have a more flat system and just list hundreds of competencies that students must master. In a hierarchical system, measuring the key sub-parts gives you some information about the whole, but it may still be necessary to measure the whole when sub-parts interact with each other.

I'd consider this to be the very purpose for our existence. Thus, I agree these accomplishments are quite valuable. If our mission is valuable to us, do we not need to know if we’re actually accomplishing our mission? How do we do that, other than to measure in some way?

Are these achievements measurable? Sure, as long as we agree on what success looks and how we (operationally) define these accomplishments. Only then can we develop appropriate tools to measure them. Are these achievements easily measurable? Probably not, but that shouldn’t stop us since we already established they’re highly valuable. These are complex accomplishments, which probably will require multiple measures to provide sufficiently comprehensive data to help us determine how well we’re accomplishing our goals. It may not be feasible to measure some achievements directly, but can make a reasonable approximation through triangulating a series of qualitative and quantitative indirect assessments.

I appreciate instructors who are willing to closely examine their own educational contexts, try recommendations, carefully evaluate the results of the experimentation, and use evidence to support what to keep and what to discard in the future. To me, a scientific mindset towards education is the essence of assessment.

When considering educational issues, it is important to remain mindful when collecting, interpreting and using evidence to ensure we’re making good decisions. I’ve seen huge changes to instructional approaches result in minimal change in student learning while seemingly minor alterations have massive impact. Compared to some "hard" sciences, Education is “messy” because it is much harder to identify and control the diverse variables including all the traits that instructors, students, institution, culture, physical environment, discipline, etc. bring into every educational interaction. Education, as a discipline, uses various methods to have reasonable confidence in what we can assert about teaching and learning; yet, there will always be an unpredictable component. Experts in the field may provide guidelines and best-practices, but these usually must be adapted to the unique considerations for each classroom.

In summary, the guidelines are there for a reason and should be backed by empirical evidence. But, when applying guidelines, it is not unreasonable for an instructor to critically evaluate the guidelines and experiment with adapting them to his or her unique situation and goals.

Although the story happens in the past, I narrate it in the present tense in order to draw a contrast with the previous experience I mentioned (My visit to Quincy with my parents). I had a huge tense issue in the first draft because I was very confused about how to contrast something in the past with other things that happened even before "the past." Brian suggested me to try to change my lonely experience part into present tense and see how it goes. I made the change and kind of like it. The tense difference divides my essay into two chunks which is just what I intended to do at the beginning. My essay also gains a clearer structure this way.

In my first draft, I summarized a lot about the content of Carson's essay and wrote little about my insights. But I realized I should include my own perspectives and inquiries in my pieces of writing. So I added two paragraphs in which I expressed my opinions and asked questions. Writing isn't just about responding to questions that your teacher gives you; it's about letting your curiosity lead your writing and asking thoughtful questions.

Discussion Forum - I believe using a technology like the discussion forum allows for students to expand on their thinking and interaction. I know I often think of things I wish I had said after class; students tell me the same thing. This forum allows for students to respond in their own time and ponder what they want to say. It provides a more equal platform, as some students may be reluctant to speak in class and others just process things for a longer period before responding and may rarely speak in class. Some of our class discussions in ENG101 would take the place of an online discussion assignment later in the week. Many weeks, these discussion questions would be generated from what we discussed, or didn't have time to discuss, in class, as well as concerns I see with skills or that the students have with assignments. This is why only a few weeks have been posted as examples.

This piece of the passage is particularly eye-catching to me because as a student here I too examine the break down of the overall cost of attendance. The 5 provisions from back then resemble the ones we have now (minus transportation and technology). Once again I see a scam brewing. I feel as though this is just a way to cover up the extra cost they may be requiring the attendants to pay. As to if those expenses actually go into what they claim they are is solely based on the designers of the provisions. I think this is something worth looking into with the recent news of UVA trying to raise tuition.

These sentences seem to form a little bit of a contradiction, in that at first the report says that the arts are important/valuable, but then saying they need not be "incorporated with the institution." Nonetheless, they do show some thoughts about the arts back when UVA was being founded. In my current engagement class, Art: Inside/Out, we always discuss how art comes into play in our daily lives and how people view art on large and small scales. I see these same themes in this part of the report, because it is reflecting on how the commissioners see art and for what purpose they think it serves. In this case, its seems the purposes are either for military use or plain enjoyment. I believe if we asked the University community what the value and purpose of art is today, we would see a stark contrast to this, as well as an extreme variety of answers. Many people would say that art might be to spread a message or support some larger movement. Today we see the presence of art so much at UVA, such as through musical and theater groups, public art installations like the curiosity shop, or the mural on the side of the Graduate Charlottesville Hotel.

I love this sentence because of how it's formed and narrated. At the same time, there's reflection for the incidents caused by white supremacy in nowadays society. We may think that the discrimination between race is deeply rooted in the earth that we may never eradicate it, however, as it's said in this sentence, some trees are so uncultivated that people think there will never be sweet fruits being yielded, but we ignored that the most elegant and persevered spirit is generated from the most savage earth, because the spirit of fighting back. That's exactly how America was born, through the voice against tyranny and the gun toward invasion, by which a colony was transformed into a nation through nirvana.

While it can show that 95% of people begin smoking before they turn 21, does that mean that it will change even after this law happens?

Clearly the frame workers of the college put considerable weight upon the learning of foreign languages. I admire the kind of insight that the writers had when nothing that the German language lead to considerable advances in sciences. During the time in which this was written, it was not often considered as to how language changes the way you think. There are many distinctions that come from speaking a different language, some obvious, many very subtle and elusive. An example of this would be the fact that German speakers often focus on goal oriented details when constructing a sentence because the nature of their verbs are not as versatile as in English. Studies have shown that Germans can predict goal oriented behavior better when viewing an action, while English speakers focus more solely on the actions themselves. This is a subtle distinction, but it evidences that the differences exist, and these differences can culminate to big implications in terms of ways of thinking. To bring this full circle, UVA requires me to take a foreign language; but UVA has also come to the point in which they offer classes that study specifically Language and Thought. This may not have been in the original plan, but has become an offshoot based upon the broad curriculum that was originally setup for the school to branch off of.

This is an interesting passage because it addresses the idea of self governance, which plays a pivotal role in UVA culture. At UVA, we as students have many roles in making decisions and advocating for the rights of the entire student body. However, another interesting point is brought up with the concept of fear and whether or not that is an effective way to govern people. While I do not believe that it is the necessarily right way to govern people, I do think that it is inevitable because so many of our actions are based on fear of consequences. Even the honor code, which represents a large part of UVA's identity can be seen as governed by fear. We can ask the question of whether or not people uphold the honor code because they really believe in honor or if they uphold it because they fear the consequences of breaking the honor code.

This mentions the salaries of the professors, but I did not see any discussion about other faculty members. I wonder if they purposefully did this. In my current engagement, we discussed how knowledge can be withheld for various reasons. We did a project in which we tried to find the origins of our dining hall food, who cooks the food, and how much these individuals get paid. It was difficult to find some of this information. Through our discussion, it became clear that universities and corporations often make it easier to access positive information than negative information. This controls the perception one creates. I think they may have only talked about professors due to the presence of unpaid labor in the form of slaves. Although, we know they had slaves, it seems clear that they did not want to draw attention to this.

This line also states that the professors’ salaries will be from the tuition fees. This also relates to my engagement as we discussed the rising cost of tuition and how some universities are transforming into business as they prioritize money over education. I do not think that this was the case when the Rockfish Gap Report was written as it discussed the ideal version of the University. Therefore, it would embody the characteristics that Jefferson frequently emphasized, such as the importance of an education. However, it is important to realize how the intentions of a university shifts as time progresses.

This sounds like the general requirements we take now; certain subjects are required for students to take. I think it is interesting that they said “certain science shall be taught.” This suggests that they are trying to control the topics that the students learn about, molding them into what the school thinks they should be. I think students now have more freedom in what they study. The university offers a large range of subjects, and the student decides what they want to study. This allows students to pursue what interests them. The document indicates that this was not previously the case. This could be problematic, as students may not feel passionate about the science they are forced to take, or they may have a skill that is overlooked because it is considered less important.

I think this sentence in particular demonstrates the ambition and hopefulness of the University founders. Anglo-Saxon language is to be emphasized because it forms the foundation of the language with which the future achievements of the University will be recorded for posterity. This sentence demonstrates the international reach the founders intended for both the university and the nation as a whole to have. At this time the United States was hardly a global power; European nations dominated every aspect of the world's power distribution, from education to commerce to the sciences. The sentiments set forth in this sentence and the report as a whole would have seemed impossibly ambitious at the time but are vindicated in the present. The founders new that the key to American success on the world stage was the success of American education. I think we owe a great deal of our current wealth and power to the foresight of these educational pioneers.

I realized that although there is a form of government present in the United States at that time period, the founders of the university noted that there is yet to be a government within the university itself, so I think the founders believed the country's system of government is flawed and not appropriate to have at a institution for young adults. Now, we have the honor committee which is entirely governed by students and instead of imposing a sense of fear upon the students, the honor committee encourages for students to uphold their integrity. Like the report states, fear cannot produce good character since it is linked to corporal punishments and humiliation. I agree that fear is a negative connotation. In my engagement class, Art Inside/Out, I read an article written by African American, Evelyn White, who had a fear of the wilderness due to the threat of potential danger from white people. Being away from society made her initially realize that wilderness is not always beautiful nor admiring. So it is important not to evoke fear within the students.

Since arriving at the University, I have found myself wondering what Jefferson would think of the University as it is today. We have preserved the original Academical Village along with other aspects of the University, and the New College Curriculum seems to be a re-kindling of his philosophies. The goal of the Engagements is to challenge us to think across subjects and globally. After such tremendous growth, how has the University's educational philosophy changed, and are the Engagements an attempt to return to Jefferson's original vision?

This passage is focusing on always looking forward in terms of society and civilization, instead of mourning for the past (in relation to the indigenous people at the time). For example, this may translate to someone today thinking civilization should go back to the way it was before cell phones ‘ruined everything’. This passage is against that idea, because everyone should try to better society. However, this makes me think of the argument between STEM and Arts courses. While one shouldn’t stay stuck in time and constantly wish for the past, that does not mean they should ignore it. As we often hear, ‘learning history helps from repeating past mistakes.’ The way this sentence is phrased makes it seem like looking at the past has a negative connotation. There should be a balance of innovation and industrialization, as well as truly appreciating and learning from the past. Even if we might have more advancements and technology in this age, we still have a lot to learn from the past. Thus, the way the previous few sentences were framed denouncing indigenous people was uncalled for and only took away from the argument.

I think what Nietzsche is saying is that people who believe they have seen deeply into the world do nothing but prove that we are a superficial race. These people believe they have a deeper wisdom and more profound understanding of the world but this is in fact untrue. They feel that they NEED to uphold this image. Nietzsche recognises that some people may be born slightly different and understand things differently to others however these people seem to get enjoyment out of life only by falsifying its image. Nietzsche does not believe in this heirachy of people that feel they have a better understanding. All it is proving is that man is false.

I think it is very interesting that the writers of this document recognize that peoples' opinions on education differ. I think it is also very noble that they refer to these individuals as "good men, and even of respectable information." It shows that the authors do not believe that their own opinions and values are absolute truths, which is a mark of a truly educated individual. Arguments like this one still continue today. For example, many people do not believe that college is necessary, only that people need the information sufficient to succeed in their own lives. Arguments like this will probably continue for many years because there is no clear answer to this question. I believe it is important for us as a university community to realize that this is a complicated topic, and we should respect the opinions of others in regard to it, just as our founding document did.

It seems as though racism against people of color is the main thing projected by the media, when some issue occurs that allows that projection. We almost never here about any form or racism that white people may experience. It would do some good to get the other side of the story, exposing us to the truth; that our society just is not as perfect as may think.

It is very interesting to see how the founders of the University thought of the best mode of government to handle misconducts. I found it very surprising how aspects of improvement (such as pride of character, moral disposition) were preferred over fear. In addition, why would they think that fear would be ineffective at this certain stage in life and not earlier such as in high school? Nevertheless, this notion still holds true today. Authority figures would be more willing to use corporal punishment/fear as a motivation for students at earlier in life but use more understanding techniques in college due to more mature minds.

I feel like the debate of whether or not education should be private and individual is not something we look upon highly nowadays. Now, if you are unable to get an education you are looked down upon, I feel like homeschoolers even get a bad rap. It is interesting that back when this document was written you were considered of high class the more private your life was.

The debate of whether or not to include the sciences in curriculum seems to be an ongoing debate throughout this document. I think nowadays the sciences are considered more essential than the humanities but back then the more "practical" subjects were of value.

In an article I found about the importance of arts being included in education states that “Arts experiences boost critical thinking, teaching students to take the time to be more careful and thorough in how they observe the world”. I found this segment of the report to be interesting because it is the only segment that regards the university attitude towards the arts. The language of this segment is very passive, and does not imply its importance, rather it finds these activities to be more of an optional pass time. The authors of the report refer to the arts as "innocent," implying that they are childish and not the foundation of a mature job. However, I am not surprised that this was the view towards arts in that time period because their society, especially for men, was to get an education and job to provide for their family and community and arts was never involved with that idea. That being said, these days we are getting much better in recognizing its importance in actually helping “critical thinking”, this boosting achedemivc education as well as happiness and morality. I find that arts education produces well-rounded students that think holistically, contradicting the reports depiction of the arts being more extraneous.

https://www.edweek.org/ew/articles/2014/12/03/13greene.h34.html

It had never occurred to me that at this period in time there wasn't really any precedence in how colleges should govern and discipline the study body. After further thought it makes sense because there weren't really that many colleges available at the time. Also, it is interesting that they thought fear would be a good way to keep order among the students. Currently at UVA it doesn't seem like they govern us with fear, but when you think about it, the threat of getting in trouble by higher authority is a form of fear. This fear of getting sanctions or getting expelled from college helps to keep students from doing things deemed unsavory by the university such as drinking in dorms or other disorderly conduct. This is now the norm for how to deal with these issues at colleges and it appears it hasn't changed much since the beginning of UVA.

This brings up the topic of whether what is being taught is actually helping create good people. the commissioners not only want to educate people, but create people that will better society. They have to decide on what curriculum will allow them to do both of these at once. This sentence presents a good argument that will probably be revisited. With the advancement of technology, many task that we do now may become obsolete. Will school teach students how to use machines, or continue with the path that they are on now?

The introduction was very informative, I don't know what is your thesis statement and what your essay is going to be about here. I think you should give the reader and idea of where your going, maybe if you started with a Cover letter?

Summary: Judges deals with the state of Israel in an independent manner.

This assessment of education by the writers shows their view on how transformative it can be. They describe education as a way to find moral guidance. They also bestow upon it credit for the advancement of civilizations. The first part is rather interesting because it assumes that before education, man is mean and immoral, by his untouched nature. In modern times, we might think of that statement as unfair and unreasonable. This may be an issue with differing definitions of education, however. Ana Bakke.

After this semester, I understand better why languages are the foundation common to all the Sciences. In the COLA class I took, we discussed what the differences between squirrels and humans. I think it is the languages humans created that make a remarkable difference. Humans learn to communicate and share ideas with languages. Sciences are based on collective thoughts. Languages enable people to learn and build on each other's ideas. This was a step towards greater efficiency.

It still amazes me that the university's location was based on the proximity to the white population in Albemarle County. For the times, this statement was extremely normal, and this is seen in the way the sentence is written. First, the mention of the "healthiness" of the site (something we may consider reasonable today), then the "fertility" of the next country (as Virginia has always been an agricultural state), and finally the "centrality to the white population" (as if this is just another plain thing to consider). Although we have moved away from this very direct form of prejudice, the history is still there. There are still people who think this way in our society and especially at the university.

I chose to annotate this sentence because it goes hand in hand with my other comment from this section. I think this should continue to be one of the primary goals of higher education. Although it should probably be a goal of ALL education, that may not be realistic at this point in time. Just as political efficacy is often tied to voter turnout, and political efficacy is often tied to political understanding and knowledge, our institutions should have an influential hand in educating us as a citizen. The best way for us to impact, develop, change, inspire others is through politics (not meaning we have to run for office, but in participating in some way). I am glad that UVA had this as a core goal. Maybe it is time for our administration (if they aren't already) to look back on this founding document and set a vision/goals for the future that tie in to the positive aspects of this report.

Debates similar to this still continue today. Many people still question whether it is better to go to college or a trade school and whether it is better to go to private schools, public schools, or to be home schooled. The fact that this continues to be a topic of debate means that it is something that is complicated and most likely does not have a concrete answer. I having these differences in opinions means that there should be options of all types like we have now because different types of education will be better depending on the individuals.

We see the paragraph start with a pushing off of nature, as an excursion is being slightly rescheduled. But, we can immediately see the bouncing back of nature as something necessary and inescapable, pushing its way back into the story, illustrating how the story cannot go on without the presence of nature. I think it is also interesting what power is given to nature as a healer, and miracle worker, as Brontë is once again giving control to nature. The way she does this almost generates thought about whether the characters are drawing on nature, or nature is simply drawing from and illustrating their emotions. The idea that the story must give credit to nature, and continue its journey as a novel alongside nature may imply more than simply the characters in this story, but the role of nature in society as overlooked and yet so substantial.

Holy Moly--this is Google Glass he is describing!

I think this an interesting point considering how casually some may view education to be. Once we learn new information, especially that which sparks our interests we begin embedding it into our everyday actions and/or thoughts. And not only does it change our personal lives, but it contributes to how we treat those around us. - Kayla Thomas

Joseph Chamberlain was a conservative person who advocated imperialism of England. Although he was not a prime minister, he was very influential in British political field during that period. He was conservative in terms of foreign policies but he was never an extreme conservative. He believed that he could achieve peace through imperialism.

i definitely see where people can see the negatives in IDS. as a nursing major, there weren't many of us in my class. we all went through the same classes since freshman year and all felt the same amount of pressure. on the IDS side of things, i think that you get a sense of community from a different perspective. everyone in IDS is open-minded; everyone wants to know a little bit about everything. no one is opposed to learning new things. i think that IDS creates a sense of individuality that you wouldn't normally get in the traditional education that colleges give you

I can't say that I have ever dealt with an extreme illness, such as cancer, but I have met a lot of people suffering from cancer. I have expressed my sympathy and empathy for the many patients as much as I can because I truly feel bad for them and am sorry that they have to deal with this. It is quite normal for people to express sympathy and empathy for people that are suffering from cancer as we know. However, it is not common for people to think of what those suffering are thinking of others. This statement by Sherman Alexie is very interesting because it is something that I can see many cancer patients feeling towards others and the envy that they may feel towards them.

I can support to what Joshua said about double identity, we as humans tend to act differently when our identity is not been shown to the public. We tend to behave, act , or even think differently because we aren't afraid of what people may say or think of us.

When I first saw this study I though it seemed ridiculous so I decided to use it for this assignment. I thought it seemed pretty far fetched to say that three minutes of a game could stop all cravings. It turns out that the study mentioned in this article was called “Playing Tetris decreases drug and the cravings in real world settings.” It was written by Jessica Skorka-Brown and published in Elsevier’s Addictive Behaviors book. The study was compromised of 31 undergraduate students who were supposed to report any kind of cravings over the course of the week. 16 students were supposed to play tetris for 3 minutes if they had a craving, and then report how they felt after playing. The conclusions were consistent throughout the whole week, and it did curb or lessen cravings. So the data in this study was actually pretty well represented. However it doesn’t say anywhere in the study that tetris definitively stops cravings for sex or anything else. So I looked up more studies on it to learn more about it. In other studies some cravings went away and some didn’t change at all even after playing tetris. But the overall point is that playing tetris creates imagery and the brain begins to problem solve on a very simple level. This distracts the brain from whatever it was craving before. However all these studies were done on just regular people who didn’t have addiction problems. It would be interesting to do this study on alcoholics or drug addicts and see how strong of an influence it has on them.

Citations-

Marks, G. (2016, May 05). These Are the 8 Dumbest Research Studies of 2016 (So Far). Retrieved November 07, 2017, from https://www.entrepreneur.com/article/275060

Osborne, H. (2015, August 13). Playing Tetris for three minutes stops you craving sex, alcohol and food. Retrieved November 07, 2017, from http://www.ibtimes.co.uk/playing-tetris-three-minutes-stops-you-craving-sex-alcohol-food-1515379

Brown, J., Andrade, J., Whalley, B., & Mayab, J. (2015). Playing Tetris decreases drug and other cravings real world settings. In Addictive Behaviors (Vol. 51, pp. 165-170). Elsevier .

In this paragraph, Carr uses an ethos appeal to explain the use of google articles. Carr uses big names like the University College London to give credibility to readers. It assures readers that it is not an assumption that readers "skim" more often than not.

I couldn't have cared less about history when I was in high school because I didn't see it's relevancy. As an adult, I am fascinated by it and by how little our leaders seem to know about it........... sigh

I don't think there's a link between alteration of deeply buried sediments in this study (i.e. oxygen isotope measurements from millions of years ago) and current rates of temperature increase (directly measured from satellites and weather stations). It may challenge the way we work out sea temperatures (although as I will note later the paper seriously overstates its case), but this doesn't change the observed rates of change in the post-industrial era. This is inaccurately presented.

Throughout reading this article I couldn't help but laugh at the dramatic irony of our experience as students in 2017 reading Bush's predictions for the future of mechanics and technology in 1991. He speaks with a bit of wonderment, obviously trying to shock the reader with ideas considered fantastical at the time and then undermining them as "not so fantastic;" the joke of course being that even his most fantastic ideas seem rudimentary to us. That is, until I reached this part of the article, where Bush's predictions seem to have closely aligned with those of our own in the modern era. In this quote he seems to suggest a total departure from the tactile, oral, visual, and so on. Whether explicitly or not, Bush is referencing transcendence of machine (mechanical or digital) which, when you think about it, is a "fantastic" notion even by our standards of technology in 2017.

The Kennedy Donovan Center located in West Yarmouth offers an array of services for families here on Cape Cod. Heathy families is on as well as Early Intervention services. They are able to come to you as well if that is what is needed. I think this is a great Non-Profit that helps many families who may struggle with how to raise their child. They offer different workshops for teachers as well. This program is open to all families here on Cape Cod as well as Plymouth, New Bedford, Blackstone, Attleboro, and Foxboro. With this many locations they serve a lot of people in the community.

Healthy Families. (2017). Retrieved October 24, 2017, from https://www.kdc.org/services/healthy-families/

Part of the problem in academia over the past few years, it seems to me, is the introduction of a distinctive language about harm. Three of the flashpoints laid out here – trigger warnings, safe spaces, and microaggressions – are new terms used to label phenomena and institutional remedies that have existed for some time. In my experience, virtually all faculty would be willing to excuse students from a class if some personal trauma they experience makes it difficult for them to discuss a particular topic. Similarly, it is hardly novel to contend that certain types of discussions are okay in the classroom but out of bounds in, for instance, a campus gathering place for minority students. Even during the wave of multicultural activism on college campuses in the 1990s, however, these sorts of things weren’t labeled.

This is, as this chapter notes in a few places, problematic. Faculty may be completely willing to let students know that some course content will be disturbing may bridle at the use of the term “trigger warnings.” The concept of “safe spaces” is easy to lampoon, as this chapter notes. And talking about “microaggressions” can have very different results than talking about inadvertent or careless remarks, offensive behavior, and the like. The University of Chicago example here shows this – it is not that uncommon for schools or academics to denounce “safe spaces” while simultaneously providing them.

There are a couple of more serious matters raised by these terms, however. First, the use of this sort of language can serve to polarize or to mark out different sorts of camps. This echoes a point made by Michael Oakeshott in The Politics of Faith and the Politics of Scepticism: we often change the words we use to mark certain concepts as “ours.” So saying one is for or against “trigger warnings” says little about what practices one actually pursues in class. It says a lot, however, about one’s politics and the side one is taking in contemporary campus conflicts.

Second, language such as this presumes that one can measure certain behaviors. To take the example of microaggressions – to talk about minor snubs, casually offensive behavior, insensitivity, and the like is to talk in an imprecise way about a sort of feeling one gets. To talk about microaggressions presumes that these are discrete violations – such and such person has committed x microaggressions during the past week. To measure and label things this way seems to invite some sort of disciplinary response or sanction.

These two matters are not necessarily bad – but they presume, I think, some sort of call for a response by college administrators, and they presume that our discussion shifts from talking about campus climate or campus culture to talking about individuals’ violations or rules or norms.

There is a strong argument that the preservation of documents by digitisation of documents is valid from the perspective of access ability and providing a protective source for rare books. However, this negates the social value of libraries in the community. Technology will never replace the intellectual value of manual reading as this stimulates brain activity

These two paragraphs work very well as an introduction to the simulation, esp. in terms of laying out your methodology and making clear what can be uniquely achieved w/ a digital publication. I think we should add a version of this to Ch 1. OR use these paragraphs there and add a shorter version here.

I think this statement asserts the organizations position as an independent entity in what they will advocate for. While they may work with other groups, they will not be tethered to any person or group, financially or through loyalty. They have their own agenda. This may make their work and causes seem more rooted and less driven about by politics.

Here, I disagree with the author's interpretation of the respective interview transcript. The author claims that this situation is problematic because Yosef is not studying the Torah, so he is not keeping his mind occupied with positive thoughts. Personally, I find this to be extremely unreasonable because, logically speaking, one can only keep their mind occupied for so long; there is bound to be at least one fleeting, ephemeral moment--that even those who do study the Torah--where the individual simply thinks of nothing or comes across a [negative] situation where it is only natural to think of such an event. Interestingly enough, Rabbi Dov even states in the passage that "When...we have nothing to think about, we think about stupidities." Thus, I find it irrational to assume that not studying the Torah is a chief problem for Yosef's situation when thinking [about "stupidities"] is as ubiquitous as it is. Instead, it may be more sound to assume that Yosef's troubles stemmed from his trauma from that sudden accident with the woman that caused him to actually think and process the scenario; thus, causing Yosef to truly understand and question the meaning of life and the timer over everyone's heads for their respective "expiration dates" because death in unavoidable.

Two things to keep in mind about Gosson. One, he’d written stage-plays himself—he speaks of Catiline's Conspiracies as a "Pig of mine own Sowe”—and had recoiled in horror. Two, he loved trash-talking the gods. “Iuno crieth out in Seneca ... Let’s dwel in earth, for heauen is full of whores.” And “Apollo is a buggerer.”

Stephen Gosson makes no complaint of Athena in The School of Abuse (1579), saying only that Maximus Tyrius "attributeth the beginning of vertue to Minerva."

But this passage, from Playes confuted in fiue actions (1582), appears to be what Waugh has in mind:

“If their Gods be to be honoured, but theire Gods are by no meanes to be honoured, therefore theire playes are by no meanes to be receyued. [De spectaculis] Tertullian teacheth vs that euery part of the preparation of playes, was dedicated to some heathen god, or goddesse, as the house, stage, apparrell, to Venus; the musike, to Apollo; the penning, to Minerua, and the Muses; the pronuntiacion and acton to Mercurie: he calleth the Theater Sacrarium Veneris, Venus chappell, by resorting to which we worshippe her."

Waugh has carefully not quoted this relevant bit from Gosson: “Tertullian affirmeth yt Playes were consecrated vnto Bacchus."

Clearly Stubbs has plagiarized Gosson, almost word for word. And in turn, Gosson has warped the early Christian moralist Tertullian, who writes:

"At first the theatre was properly a temple of Venus. ... But Venus and Bacchus are close allies. These two evil spirits are in sworn confederacy with each other, as the patrons of drunkenness and lust. So the theatre of Venus is as well the house of Bacchus: for they properly gave the name of Liberalia also to other theatrical amusements—which besides being consecrated to Bacchus (as were the Dionysia of the Greeks), were instituted by him; and, without doubt, the performances of the theatre have the common patronage of these two deities. That immodesty of gesture and attire which so specially and peculiarly characterizes the stage are consecrated to them—the one deity wanton by her sex, the other by his drapery; while its services of voice, and song, and lute, and pipe, belong to Apollos, and Muses, and Minervas, and Mercuries."

Venus and Bacchus are blazingly the leads in this company; the rest of the pantheon is "also appearing." They're not even named as individual deities, but dismissively as types: "Apollines et Musas et Minervas et Mercurios." Tertullian is so hostile to the pagan gods that he lumps them together as "Apollos, and Muses, and Minervas, and Mercuries." And so forth, and so forth. They're certainly not assigned individual roles. He just treats them all as gangs of devils.

You will note that writing isn't mentioned. Hardly surprising, as Tertullian's real target is the Roman Games: the circus, the gladiatorial combats. What he loathes is spectacle.

So Gosson has to translate Tertullian's attack on an alien recreation into terms related to Elizabethan playhouses: not known for blood sacrifice or dazzling spectacle. Gosson has tried hard to rationalize that passage; he’s tried to attach an action to each god. But Minerva has no mythological connection to the theatre at all: her oversights are the strategy of war, wisdom, weaving. She's there in Tertullian simply as a abomination for Christians to shudder at. Gosson has to invent something for her to do, and “penning” is the closest he can come. (Of course, "penning" is what he himself did in his brief association with the theatre, so he may well have a particular aversion to it.) The Muses, of course, include Thalia and Melpomene (Comedy and Tragedy), so he clumps her with them. In short, when he tells us that "euery part of the preparation of playes, was dedicated to some ... god, or goddesse," he's confabulating. Making stuff up.

In this tract, Gosson is explicitly replying to Thomas Lodge's A Defense of Poetry (1579). Lodge had just pwned him:

"But tell mee truth, Gosson, speakest thou as thou thinkest? what coulers findest thou in a Poete not to be admitted? are his speeches vnperfect? sauor they of inscience? I think, if thou hast any shame, thou canst not but like and approue them: are their gods displesant vnto thee? doth Saturne in his maiesty moue thee? doth Iuno with her riches displease thee? doth Minerua with her weapon discomfort thee? doth Apollo with his harping harme thee?—thou mayst say nothing les then harme thee, because they are not, and, I thinke so to, because thou knowest them not."

"Thou knowest them not." Why on earth would the allegedly well-educated Oxford take a name from an error propagated by a frothing fool?

In short, the only early modern writers who in any way attach Athena/Minerva to any aspect of the theatre are Stubbs slavishly copying Gosson misreading Tertullian who hated all the gods.

This is especially incoherent. What I think Waugh has invented here is a generational right to a certain spelling of a family surname: you don't get to be "Waugh" until your grandfather dies. As he imagines it, the great-grandfather would use "Woch," the grandfather, "Waugh," the father, "Wauch," and the son, "Waw"-- and when the "great grandfather died he moved up a line": so Alexander Waw would become Alexander Wauch, and Auberon Wauch become Auberon Waugh.

Sheer rubbish.

Ralegh is a bad example. His father died in February 1581, which matches none of Sir Walter's changes in orthography. "Down to 1583 his more usual signature had been the phonetic Rauley. But in 1578 he signed as Rawleyghe a deed which his father signed as Ralegh, and his brother Carew as Rawlygh. A letter of March 17, 1583, is the first he is known to have signed as Ralegh; and in the following April and May he reverted to the signature Rauley. From June 9, 1584, he used till his death no other signature than Ralegh."

This is a dodge. Camden knew Shakespeare as a player, and knew the works of Shakespeare, listing him among the "most pregnant witts of these our times, whom succeeding ages may iustly admire."

There is no reason to imagine that Camden thought that the player and the poet were two different people; indeed, he may well have met Shakespeare. Camden was cited by Ben Jonson as his teacher, apparently when Camden was headmaster of Westminster school, and Jonson wrote plays that were performed by the Lord Chamberlain's Men and King's Men, Shakespeare's playing companies.<br> http://www.shakespearedocumented.org/file/details/329

Here I believe Popper is saying that every individual has a predisposition towards the world. Be as that may, that does not define how a person sees the world, but rather their general inclination think.

While assessing historical documents like the Rockfish Gap Report, we must keep in mind that not everything should be taken word for word. Like the U.S. Constitution, the Rockfish Gap Report is a living, breathing entity that must evolve over time. Although Thomas Jefferson may have initially intended for there to be a small, fixed number of professors, our University has expanded greatly since the publication of this document. We must always consider the context in which a document was written before we decide on what principles of the document should be applied to the governance of our modern community. Clearly, to accommodate the student body that has grown substantially in the past two centuries, it was crucial that more professors were hired.

It is very interesting to see that many of valuable subjects to learn at the time are still very important today. In modern times the methods of how these subjects are taught are more complex in the sense that multiple professors contribute to the teaching of a particular subject. Also in today's times there may be different courses under a key subject that focus on different aspects. The learning system that was in place at the start of the university seems to be ore structured , while today it is more flexible.

I think this passage is extremely significant. The University was hoping to train and educated young people so that they could then go on to lead and run our country. They wanted the most educated people to help shape society because they hoped this University would give them good morals and teach them valuable lessons. I think this is ironic due to the fact that the majority of politicians working in the government have very corrupt morals. A lot of the people working in these offices lied their way to the top in an attempt to gain power. It's no surprise that our government has corruption in it. I think that if all Universities strove to really educate their students on good moral and values, we may try to prevent this corruption and obviously the authors of this document agree and tried to help create a government that would be beneficial to the country as a whole. Maybe we will be the generation to follow out their desires.

It is interesting how similar debates about education carry on today about whether private schools or homeschooling is better and about what subjects should be taught. The idea of students having experience in a variety of subjects and becoming well rounded is an idea from this report that also persists today. The fact that we are still trying to figure out the best forms of education shows how education is not just black and white and that there is no single form that will work for everyone.

Today, UVA can be known as a pretty liberal, diverse university, so it is unfortunately ironic that it was founded on a principle of “centrality to the white population” of Virginia. While it is obviously known that during this time in history racial prejudice was quite evident, everyone would like to hope that the place we know and love today has always been a place of equality and acceptance. That is not the case, however, as shown in this passage that is aiming for a location that is most convenient for white people, not taking into account any of the other “races” that make up the melting-pot of America. I put the word races in quotations because in my engagement “Evolution and How it Shapes Society,” we learned that race is actually somewhat of a social construct. Humans are around 99.5% genetically similar, and our difference in skin color, among other differences in appearance, have occurred in response to the migration of humans to different environments, where, for example, UV rays may not be as strong. This is interesting to think about in response to this passage because it is absurd to think that certain people’s exposure to UV rays made them more favorable to receive a quality education.

I remember coming to UVA for the first time and hearing my tour guide, Joe, talk about Jefferson's idea of an academic village where students and professors lived amongst one another. That was one of the first things that drew me to UVA: the strong sense of community. And I think that it still holds true today. I'm proud to be part of the Wahoo community because I know that someone will always have my back. UVA may be a great school academic wise, but I think its strong sense of community (which has been there since the very beginning) is what sets this university apart from the rest. Learning what it means to be something bigger than yourself is an invaluable skill, especially in this individualistic society. Even though we are first years, we must take advantage of this inclusive community and work together to raise this university higher and further promote the idea of equality in the society around us.

I think it's amazing how much consideration went into the planning of the living arrangements. Jefferson's plan had great emphasis on comfort and education. His plans also took into account potential problems like fires and sickness. I think we as a community at UVA overlook how much time, effort, and consideration went into each detail of where we live and learn and it's nice to look back on this report to see where we started.

Preach!

In executing their duties to organize and govern the University of Virginia, the Commissioners created 5 provisions for the education of the youth. Of interest is #4, in which the Commissioners discuss in length how best to govern the students. Wisely, they deduce that "fear" does not create men of "erect character." Instead, they believed the act of appealing to one's "pride of character" and "moral dispositions" when governing young men would better produce the desired effect. The Commission further supports their position by saying that ideally the tutor/pupil relationship should emulate the father/son relationship as the best means to motivate and govern the student body. "Fear" and "corporal punishment" are merely degrading methods of governing and should be avoided in all situations. I believe in the US education system fear is used to much for motivation and I think it is completely unproductive!

The process of characterizing physical attributes is a very straightforward and seemingly uncreative, which may be unconventional for writers. Interestingly enough, computers thrive on performing logical tasks. In a TED talk in 2015, Fei-Fei Li talks about making computers able to understand images. Similar techniques have even been used to read people's dreams, where electrical signals are logged and arranged as an image, and a computer attempts to characterize what the person was "seeing". Researchers from the University of Illinois at Urbana-Champaign took it a step further and wrote the paper "Describing Objects by their Attributes". In it they discussed how they were able to "develop computer vision algorithms that go beyond naming and infer the properties or attributes of objects".

In the video, Fei-Fei Li explains the process her research team used to teach a computer how to recognize objects in images. This process was started by showing the computer gigantic amounts of processed images to allow it to train. At 7:35, SHEEEE mentions that thousands of employees worked together to organize and label over a billion images. This process reminded me of the metadata mentioned by Morna Gerrard in our visit to the Archives. Much like categorizing archives helps us identify the information we want, the categorization of images aids a computer to find what it is looking at.

I think it would be interesting to have technology contributing in the first steps of Prowian Analysis, since their logical approach to solving problems might allow us to have more detailed and thorough descriptions. Perhaps one day, technology will be able to take it a step further and make assumptions about the meaning of physical attributes, allowing material culture to be partly automated.

Paper: http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.149.9539&rep=rep1&type=pdf

Video: https://www.youtube.com/watch?v=40riCqvRoMs

I feel that Becky Geller did a very good job with remaining open while writing about her sources. However, it seemed to me that in her conclusion she took a stance leaning towards not using the predictive testing.

if only computer sciences were presented in such a way - as being essential for creative projects - more youngsters would opt in for such an education

I chose the supplemental reading titled Mystery of Russian Fake on Facebook Solved, By a Brazilian. The article followed the story of how Russia created fake profiles on Facebook in order to spread Russian propaganda and denounce Hillary Clinton. A Brazilian salesman noticed that his pictures of him and his daughter were being used for fake American profiles. The profile in question was "Melvin Redick", and he would openly promote the Russian propaganda website DCLeaks.com. The NY Times tried to track down Mr. Redick, but upon further investigation, he did not seem to exist. After the Times reported this to Facebook the profile was soon removed from the website. Reading this article which contained quotes from Mr. Costacurta on how he felt about his pictures being used was eye-opening. The article shows how little the Russians care for the privacy of others as well as how our internet profiles may be a lot less secure than we think. The Russian government stole the pictures of an innocent Brazilian man, in order to influence another country's election. The blatant disregard for morals and Costacura's value as a person are very evident through Russia's actions. They took advantage of how Google blocks image searches of its Brazilian users (a rule that is intended to protect the privacy of users) in order to influence the 2016 election.

As a citizen in one of these minority groups I am fearful that history may be allowed to repeat itself if we allow these individuals to preach their hate.

This letter to the leaders of America spoke numbers to me. Our country is being divided and the people in control of this country is advocating for the division. I do not think people under the severity of history repeating itself and on top of that, the one person that is supposed to protect us does not seem like he has everyone's best interest. People are literally scared for their lives. No one should be afraid to live.