On 2014 Nov 23, Harri Hemila commented:

A manuscript version is available at handle

On 2014 Nov 23, Harri Hemila commented:

A manuscript version is available at handle. The paper was commented on by Thomas Chalmers http://dx.doi.org/10.1016/0895-4356(96)00190-4 to which a response was published http://dx.doi.org/10.1016/0895-4356(96)00191-6, which is also available at handle

On 2014 Nov 23, Harri Hemila commented:

None

On 2014 Aug 10, Matthew Katz commented:

Organ preservation as a treatment strategy effectively demonstrated chemoradiation as the standard of care for anal canal cancer. RTOG proved the point in 83-14 [Sischy B, 1989]. The RTOG phase III trial above confirmed the importance of mitomycin-C as part of the treatment regimen, which remains the standard in 2014.

With the rising incidence of HPV+ anal cancer, which may have a better prognosis, an important question will be whether we should lessen treatment intensity. Further trials will be needed to see if it's possible to lessen treatment toxicity without compromising cancer control.

On 2013 Jun 13, Karl Broman commented:

This is the first paper to consider interval mapping for binary traits in experimental crosses. Somewhat surprisingly, genetic mapping in humans focused on binary traits and not quantitative ones, while mapping in experimental crosses focused on quantitative traits and not binary ones. The method is developed in the context of marker covariates, and so it is a bit more technically challenging to understand than it might be, but this paper had a lot of influence on my understanding of QTL mapping.

On 2015 Oct 21, Jeff Bertrand commented:

Looking for a full text version of this article.

On 2014 Jan 07, Brett Snodgrass commented:

Dear Reader,

The myocardial sinusoids are not a phantom regardless of whether knowledge about them is.

Arteriosinusoidal vessels described by Wearn connect to myocardial sinusoids. The myocardial sinusoids are often pathologically altered and readily apparent on microscopy in pulmonary atresia with intact ventricular septum.

Dr. Wearn's work: http://bit.ly/JTWearn The myocardial sinusoids are not phantom as they connect to the arteriosinusoidal vessels. The vessels of Wearn include the arteriosinusoidal and the arterioluminal vessels of the heart. Wearn's distinguished Harvey lecture of 1940 describes the difference between the "Thebesian veins" and the "AL & AS" vessels (vessels of Wearn). Related references: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933738/ http://www.ncbi.nlm.nih.gov/pubmed/22704295 http://www.ncbi.nlm.nih.gov/pubmed/23332812 https://twitter.com/BrettSnodgrass1/status/419324443068874752

On 2015 Aug 21, Robert P O'Shea commented:

The PubMed title of this paper is incorrect. It should be "The extraordinarily rapid disappearance of entoptic images" with two ts in "entropic", as in the paper itself. Entopic is a medical term meaning in the usual place, as opposed to ectopic, which means in the wrong place (e.g., ectopic pregnancy). "Entoptic" means in the eye, requiring the Greek root "optic".

On 2015 Sep 11, Bill Cayley commented:

More evidence that "less-medical" primary care can actually be MORE cost-effective (and perhaps better in other ways: https://lessismoreebm.wordpress.com/?s=primary

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2013 Nov 24, John Sotos commented:

[Written in 1996] Speculations regarding Creutzfeldt-Jakob disease (CJD) acquired from beef containing the infectious agent that causes bovine spongiform encephalopathy [1] have resulted in dramatic health policy measures and serious concerns in the lay public about dietary beef intake in Britain. We believe these concerns are out of proportion to the actual risk of CJD, especially when compared to other established risks of beef consumption, such as the development of coronary heart disease (CHD). We therefore sought to estimate a beef-eater’s risk of CJD and CHD based on currently available data.

The ten cases of CJD became manifest over a 20 month span in 1994-1995 [1]. If we suppose a uniform incubation period of 10 years for CJD, then all 10 cases were infected during a 20 month period in 1984-1985, when the mean beef intake among the 56 million Britons was 181.5 g/person/week [2] (roughly equivalent to two hamburgers per week). Assuming the attack rate remains constant, an average Briton would have a 1 in 933,000 chance of developing CJD from 10 years of beef-eating. The risk per hamburger is roughly 1 in one billion.

To determine the beef-attributable risk of CHD, we first calculate the change in serum cholesterol that results when the fat and cholesterol in lean beef [3] are consumed in place of isocaloric carbohydrate or protein. Using the average daily caloric intake in Britons (2040 kcal) [2], the Hegsted equation [4] predicts a 2.1 mg/dl increase in serum cholesterol when 181.5 g beef/week are consumed. For a 30 year-old non-smoking, non-diabetic man with a total cholesterol of 150 mg/dl, an HDL cholesterol of 45 mg/dl, and a systolic blood pressure of 120 mmHg, the Framingham equation [5] predicts that a 2.1 mg/dl increase in serum cholesterol sustained over 10 years raises the risk of CHD during this period by 1 chance in 5300. Thus the CHD/CJD relative risk is approximately 175!

Although our calculations are approximations at best, they clearly show that the risk from fat and cholesterol in beef is, for most of the adult population, orders of magnitude greater than the risk from neurotropic particles contained therein. Other diseases linked to fat intake, such as stroke and colon cancer, have not been considered here. Based on these data we believe that beef-eaters should care for their coronaries, rather thsn perseverate on prions.

[1] Will RG, Ironside JW, Zeidler, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. 1996;347:921-925.

[2] Ministry of Agriculture, Fisheries and Food. National Food Survey 1994. London: Her Majesty’s Stationery Office, 1995.

[3] American Heart Association Cookbook. Ballantine Books. New York, NY, 1986.

[4] Hegsted OM. Serum-cholesterol response to dietary cholesterol: a re-evaluation. Am J Clin Nutr. 1986;44:299-305.

[5] Anderson KM, Wilson PWF, Odell PM, et al. An updated coronary risk profile: a statement for health professionals. Circulation. 1991; 83:356-362.

On 2016 Jul 23, Jonathan Eisen commented:

I am posting some materials associated with this paper on Figshare (alignments, trees, color figures, etc).

See https://figshare.com/projects/1995_Eisen_RecA_Evolution_JME/15035

Jonathan Eisen

On 2014 Dec 02, Robert Eibl commented:

I worked at that time in that lab and I completed the very first isogenic SV129 K.O. constructs for the planned partial K.O of the CD44 gene. Part of my work contributed to the paper above and was acknowledged within the article: "The sizes of the PCR products derived from the phage clones allows an estimate of the intron sizes. These results have been indepentently confirmed by mapping the restriction sites for more than twenty restriction enzymes on (lambda) phage inserts(R.Eibl, unpublished results)."

On 2014 Nov 16, Robert Eibl commented:

None

On 2018 Jan 21, Tom Kindlon commented:

References:

1 Chalder T, Berelowitz G, Pawlikowska T, Watts L, Wessely S, Wright D, Wallace EP: Development of a Fatigue Scale. J Psychosom Res 1993, 37:147-153.

2 Neu D, Hoffmann G, Moutrier R, Verbanck P, Linkowski P, Le Bon O. Are patients with chronic fatigue syndrome just 'tired' or also 'sleepy'? J Sleep Res. 2008 Dec;17(4):427-31. doi: 10.1111/j.1365-2869.2008.00679.x.

3 Goudsmit, EM., Stouten, B and Howes, S. Fatigue in myalgic encephalomyelitis. Bulletin of the IACFS/ME, 2008, 16, 3, 3-10. https://web.archive.org/web/20140719090603/http://www.iacfsme.org/BULLETINFALL2008/Fall08GoudsmitFatigueinMyalgicEnceph/tabid/292/Default.aspx

4 Goldsmith LP, Dunn G, Bentall RP, Lewis SW, Wearden AJ. Correction: Therapist Effects and the Impact of Early Therapeutic Alliance on Symptomatic Outcome in Chronic Fatigue Syndrome. PLoS One. 2016 Jun 1;11(6):e0157199. doi: 10.1371/journal.pone.0157199. eCollection 2016. https://doi.org/10.1371/journal.pone.0157199.s001 (CSV form: https://www.mediafire.com/file/rvh3brmgoaznude/Goldsmith+2015+FINE+data+journal.csv )

5 A dataset from the PACE trial. Released following a freedom of information request. https://sites.google.com/site/pacefoir/pace-ipd_foia-qmul-2014-f73.xlsx Readme file: https://sites.google.com/site/pacefoir/pace-ipd-readme.txt.

6 Morriss RK, Wearden AJ, Mullis R. Exploring the validity of the Chalder Fatigue scale in chronic fatigue syndrome. J Psychosom Res. 1998 Nov;45(5):411-7.

7 Loge JH, Ekeberg O, Kaasa S. Fatigue in the general Norwegian population: normative data and associations. J Psychosom Res 1998; 45: 53-65. CrossRef | PubMed

8 Van Kessel K, Moss-Morris R, Willoughby, Chalder T, Johnson MH, Robinson E, A randomized controlled trial of cognitive behavior therapy for multiple sclerosis fatigue, Psychosom. Med. 2008; 70:205-213.

On 2018 Jan 21, Tom Kindlon commented:

My feedback on content of Common Data Elements (Fatigue) - Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) CDE Public Review

I submitted this to the NIH and thought I would also post it here.

Suggested Change: Don't use the Chalder fatigue questionnaire

Rationale: The Chalder Fatigue questionnaire has two separate scoring systems, bimodal (0-11) and Likert (0-33) [1]. Some of the issues raised below are more significant with one system rather than the other.

(i) Doubts about the validity of two of the items in the questionnaire as means to measure fatigue:

The item “Do you have problems starting things” seems as though it could relate more to motivation or some other issue rather than fatigue specifically.

The item “Do you feel sleepy or drowsy” relates more to sleepiness than fatigue. Sleepiness and fatigue are not necessarily the same thing [2].

Most studies that used the Chalder fatigue scale do not give details of scores on individual items but one study [3] reported the following in participants with ME: “Focusing on the individual items revealed that 86.8% of the questions making up the physical fatigue subscale received near maximal or maximum scores. The items which received the greatest number of low scores were question 3 (‘do you feel sleepy or drowsy’) and question 4 (‘do you have problems starting things’).”

(ii) Ceiling effects are a significant issue when the Chalder fatigue questionnaire is used with patients with ME and CFS score, particularly with bimodal scoring:

A study of those with ME [3] found that “Fifty per cent of the patients recorded the maximum score using the bimodal method and 77% recorded the two highest scores [i.e. either 10 or 11].” In the FINE and PACE trials, 76% (147/193) and 65% (417/640) respectively of CFS participants reported the highest score [11] at baseline using bimodal scoring [4,5].

With regards to Likert scoring, a study of those with ME found that there was some evidence of a ceiling effect in those who were severely affected (more details were not reported but the average score for those severely affected was 30.55 (SD: 2.66)). In the FINE and PACE trials 29.1% (57/196) and 14.5% (93/640) of the participants with CFS respectively scored the maximum score of 33 at baseline.

There is also a 14-item version of the instrument with three extra items. A study of 136 individuals with CFS looking at Likert scoring found there was near-maximal scoring on 6 of the 8 physical fatigue items [6].

The authors of the ME study [3] noted with regards to bimodal scoring that there was a “marked overlap between those who rated themselves as moderately or severely ill. These findings are indications of a low ceiling.” This could lead to the questionnaire failing to detect patients moving from being severely to moderately affected and vice versa.

Furthermore, if patients are already at a ceiling score at the start of the intervention, the questionnaire cannot detect their getting worse. This could mean that evidence of harm would not be recorded. Also, this phenomenon could affect measures of efficacy: if a certain percentage of patients improved and the same percentage worsened to a similar level, this could show up as an average improvement because the scores for those who got worse would not change if they were already at the ceiling level.

This could also make interventions that caused a significant number of deteriorations seem better than those that caused fewer. For example, consider a scenario in which one intervention caused a certain percentage of patients to improve while the same percentage, who began at the maximum score, worsened by the same amount. If another intervention caused half the number of patients to both improve and worsen, the average numerical improvement for the first intervention would be twice that of the second, even though rationally the scores should be the same.

(iii) Discussion of the ability of respondents to mark symptoms as occurring “less than usual”:

The fact that participants can rate their fatigue symptoms as occurring “less than usual” can lead to some odd results with Likert scoring of the Chalder scale (it is not an issue with its bimodal scoring). People who have no fatigue problems should generally score 11/33, indicating that they had problems ‘no more than usual’. And, indeed, a study in Norway found that those in the category “No disease/current health problem” had a mean score of 11.2 [7].

However, a study found that people with "multiple sclerosis fatigue" after an intervention reported an average fatigue score of 7.80 – that is, lower than 11; this score also showed lower fatigue than that of a healthy, nonfatigued comparison group in the study [8]. It is very unlikely to be true that patients with multiple sclerosis fatigue at baseline ended the study with lower fatigue than healthy people. Scores of less than 11 were also reported by those with CFS in the FINE and PACE trial [4,5].

I will explore further now how pooling the scores of people who give scores of less than 11 with other scores can give odd results. Say 75% of participants gave a Likert score of 4 and 25% gave a score of 24. This would be an average score of 9 which is a better score than the score of 11 that healthy people report. However, it is likely that people who scored 4 on the scale were confused by the peculiar option on the Chalder questionnaire that allows them to rate themselves as having fewer problems with fatigue than when they were last well (choosing that option is the only way to get a score below 11). If they really meant to say that they had no more fatigue than when they were last well, then their score should really have been similar to that of the average healthy person, at 11.2. Substituting this score instead of 4 in this example would give an average score for the group of 14.4, a worse score than what healthy people score. The latter is, I believe, a better representation of what the average fatigue score for the group would be: that is, if a significant percentage still had significant fatigue, than the overall fatigue level should be worse on average than a healthy group, not better. This shows that the ability to have better scores than healthy people doesn’t just affect the validity of individual scores, it also affects the validity of overall mean scores.

[The references for this comment are in my reply below]

On 2014 Nov 23, Harri Hemila commented:

A manuscript version of the paper is available at the Helsinki University institutional repository: http://hdl.handle.net/10250/8076

On 2017 Aug 20, Daniel Weiss commented:

This is a paper which is often cited to tout the robust sensitivity of the Western blot for diagnosis of Lyme disease. However, a careful, critical reading of this paper reveals major flaws. The Western blot is, on the contrary quite insensitive for the diagnosis.

I will limit my comments to study patients without recent erythema migrans. Most workers agree that an erythema migrans rash is diagnostic on its own, and that serologic tests are unnecessary as well as unreliable at this stage of the disease. Dressler performed both a prospective and retrospective study to evaluate two-tier testing. Study subjects were recruited from the authors’ Lyme disease clinic from 1990-1991. To participate they had to live in “an area endemic for Lyme disease”. The G39/40 strain of B. burgdorferi was used to generate antigens for the ELISA assay.

Dressler’s prospective study included 54 highly-selected patients with Lyme disease. The prospective group included patients with Lyme arthritis and those with “inactive” Lyme disease. Many patients had a history of the EM rash. Neuroborreliosis was diagnosed in 39 patients; these patients had CSF pleocytosis, increased CSF protein or EMG evidence of an axonal polyneuropathy not caused by other known disease. Ten of the 39 with neuroborreliosis were declared to be “inactive” although this term was not clearly defined. Importantly, only 21 of the 39 were positive by ELISA—a sensitivity of 54%. Of those cases of “active Lyme disease” who had neuroborreliosis, the sensitivity was 58%.

There were 57 patients with an indeterminate ELISA. One third of those who were thought by the investigators to have “active Lyme disease” had a negative Western blot. Thus, the two-tier test performed poorly even in patients whom expert physicians (Dr. Steere and colleagues) were sure had “active Lyme disease”.

In the retrospective study of Dressler et. two-tiered testing was performed on a highly-selected patient cohort. ELISA was negative in two of 25 with Lyme encephalopathy or polyneuropathy; two more patients’ ELISAs were read as indeterminate. Western blot testing in four of the 25 showed a minimal or absent response. Thus, the sensitivity of the test in these patients chosen because the authors were convinced they had Lyme disease reached only 84%.

On 2014 Jan 08, Brett Snodgrass commented:

Dear Reader,

This excellent study of quail embryos by Poelmann et al. also identified the vessels of Wearn.

The impression was that the vessels of Wearn are only connected to the right ventricle. However, Wearn identified the arteriosinusoidal and arterioluminal connecting to each of the four heart chambers. http://bit.ly/JTWearn

The vessels of Wearn may be appear less significant in healthy individuals, but in disease states such has PAIVS, or AA/MS, they appear more significant.

For additional commentary, please see.

https://twitter.com/BrettSnodgrass1/status/404941362908241920/

My interest is in accurate medical terminology, and I ask that others collaborate towards this end.

Comments and suggestions are welcome.

Thank you kindly.

On 2017 May 21, Kay Dickersin commented:

We need to make sure this article and others are archived properly so that they can be accessed by others. This journal was ahead of its time, and contains important articles.

On 2013 Oct 23, Pedro Mendes commented:

Gepasi is now hosted at http://www.gepasi.org . However this software has been succeeded by COPASI Hoops S, 2006 which is at http://www.copasi.org

On 2013 Nov 21, Gary Ward commented:

This report describes a simple yet elegant series of experiments demonstrating that the T. gondii parasitophorous vacuole membrane (PVM) acts as a sieve, allowing small molecules (up to ~1300 Da) to pass from the cytosol into the vacuolar space. The researchers microinjected a panel of fluorescent probes either into the cytosol of infected cells or into the parasitophorous vacuole and observed bi-directional, passive transport across the PVM. These experiments provided an important new insight into the interface between the intracellular parasite and the host cell. The likely presence of nonselective membrane channels in the PVM is analogous to the outer membrane of Gram-negative bacteria, in which membrane porins allow passive transport of nutrients and metabolites into the bacterial periplasmic space.

These results from these experiments are consistent with characterization of the vacuole membrane in host cells infected with the related apicomplexan parasites, Plasmodium falciparum [Desai et al, Nature 362 (1993); Desai and Rosenberg, PNAS 94 (1997)] and Eimeria nieschulzi [Werner-Meier and Entzeroth, Parasitol Res 83 (1997)]. The obligate intracellular microsporidian Encephalitozoon cuniculi also resides within an intracellular vacuole capable of passive transport of fluorescent peptides up to 1100 Da while 10 kDa fluorescently-labeled dextrans are excluded [Rönnebäumer et al, Eukaryot Cell 7 (2008)]. The presence of non-selective membrane channels and the non-fusogenic nature of the parasitic vacuoles established by these phylogenetically distant organisms point to a similar adaptation to an intracellular parasitic lifestyle.

Posted by Gary Ward on behalf of the University of Vermont Toxoplasma Journal Club (UVM ToxoJC); members include Jenna Foderaro, Anne Kelsen, Shruthi Krishnamurthy, Jacqueline Leung, Pramod Rompikuntal, Luke Tilley & Gary Ward

On 2017 Mar 03, Md. Shahidul Islam commented:

An extensively updated review on this topic is available: M. S. Islam. Calcium signaling in the islets. In: Islets of Langerhans, edited by M. S. Islam, Dordrecht, Heidelberg, New York, London:Springer, 2014, p. 605-632. ISBN 978-9400766853

On 2017 May 26, Israel Hanukoglu commented:

Originally we had named this protein as LL5.

This protein has been named as Pleckstrin homology-like domain family B member 1 (Phldb1).

The Uniprot link for this protein is http://www.uniprot.org/uniprot/Q63312

On 2016 Aug 17, Lydia Maniatis commented:

Short version:

The authors say: "We hypothesize that how our stimuli are perceived depends on spatial frequency. Our hypothesis is confirmed. (P.S. The effect is size invariant.)"

Translation: "We hypothesize that how our stimuli are perceived depends on spatial frequency. How our stimuli are perceived DOES NOT depend on spatial frequency. Our spatial frequency hypothesis is falsified."

a + (-a) = 0

(The discrete addition of the phrase "at one size" into the abstract, as though this did not upend the entire position, is really quite extraordinary.)

On 2016 Apr 11, Lydia Maniatis commented:

It is worth asking why, on the one hand, Solomon and Pelli (1994) seem to be asking questions about initial steps in vision - asking about "visual filters," and, on the other, referring, not to "perception" of letters, but to "identification" or "recognition." In order to identify or recognise, we have to first perceive, but this step is skipped over not only by these researchers but by those contemporary investigators who consider themselves "psychophysicists" in general.

The reason is this: These investigators insist on treating perception as a problem of detection, such that they can recycle the signal detection models first developed by radar researchers.

Thus, they assume that identification/recognition would be perfect if it were not for “internal noise” in the system, which produces uncertainty in the outcome. This noise is the random firing of neurons, base rates etc. This claim about internal noise and perception has never been tested, nor (to my knowledge) have these researchers proposed a way to test or measure the claim, but it is assumed.

It is also assumed that we can add “external noise” to a stimulus and thus counterbalance the “internal noise.” This “external noise” can take the form of variance of the stimulus pool, splotches superimposed on the stimulus (as here), etc. Anything that can be described as “unpredictable.”

If we do this, then there is an equation that we can use that allows us to measure “performance” regardless of the task, as long as we have a value to plug in for our “noise” term.

If we can assume that the “external noise” is much bigger than the “internal noise” then we can use this equation whose output is labelled “E” for efficiency, by plugging in our “external noise” value.

Clear so far?

What is wrong with this story is also the reason researchers adopting it don't refer to “perception.”

The stimulus, which consists of retinal photoreceptors excited by disconnected photons pouring in from the environment does not contain “letters” or any other objects to be “detected.” Only photons are detected by the system. It is the response of the nervous system that organizes these points, based on rules (instantiated in the system) that have been selected for over evolutionary time to produce a good enough match between the objects out there and the objects we perceive. We can understand the importance of sophisticated rules if we consider how easy it is for humans to read the letters of “captchas” used by websites to ensure you're not a robot, but which programmers have a hard time beating. (This is actually a crude and somewhat misleading example, because even seeing the entire captcha without being able to recognize the letters it “contains” is a feat of perceptual organization). So the visual system creates a percept by adding structure to structureless data, and the number of these potential structurings is infinite. The limiting factors are the rules.

So to see a letter, even as a physical shape, implies an enormously complicated process of perceptual organization, based on inferences that constitute the output of the system. What we “identify” or “recognize” is the product of these processes. We are not “detecting” something that is there a priori, in the stimulus, the disconnected photons. Seeing splotches, or any other feature of the percept, is also the result of the same organizing processes. There's no principle justifying calling part of the percept “noise” and another part “signal” if what we are interested in are basic perceptual processes. It is relatedly a problem to overlook that some kinds of “noise” will, for organizational reasons, interfere more with the “signal” that we have in mind than other kinds, something that the makers of “captchas” know well.

But all of these facts are silently overlooked by investigators who choose to treat perception as a detection problem involving imaginary spatial filters and arbitrarily defined “noise”. Which is truly extraordinary.

On 2016 Mar 12, Lydia Maniatis commented:

Continuation of previous:

Translation: Forget everything we've assumed so far about spatial filters. We don't have special detectors sensitive to the frequency of light bands falling across the retina! Visual angle doesn't matter. The visual system has special detectors for detecting the number of light/dark cycles per (familiar) "letter" - (about 3), actually a range of cycles, since some letters are quite wide (e.g. m's) and others quite narrow (e.g. l's). The processes implicit in organizing points of light into letter shapes so that we can recruit the relevant letter-sensitive channels are not relevant. Our data plus assumptions prove it.

I think this front-page Nature article has zero credible content or face-validity.

On 2016 Mar 12, Lydia Maniatis commented:

The claims the authors make in this publication lack both empirical and logical support. To make what is perhaps the most clear point, the very tenuous assumptions underlying the project are themselves contradicted by the authors own statements. This is represented as a refinement of the fundamental assumption, but in fact it pulls the rug out from under it. Each step of the way, definite assertions are made which citations provided do not support.

The train of thought (with comments) is this:

Authors: “We hear periodic sounds, or tones, by means of parallel auditory filters, each tuned to a band of temporal frequency (Fletcher, 1940)”

From MIT online Encyclopedia of Cognitive Sciences: To account for the obtained data, Fletcher proposed a “critical band” that likened the ear to a bandpass filter (or, to encompass the entire frequency range, a set of contiguous, overlapping bandpass filters). The proposed “auditory filter” is a theoretical construct that reflects frequency selectivity present in the auditory system...”

Translation: The auditory system exhibits frequency selectivity. We could find no more convincing citations with respect to auditory filters between 1940 and 1994.

Authors: “...and we see periodic patterns, or gratings, by means of parallel visual filters (Campbell and Robson, 1968).”

From Robson and Campbell, 1968: “Thus, it seems that we cannot satisfactorily model the over-all visual system by a simple peak detector following a spatial filter...As a modification of this theory, we may assume...Thus, we may suppose that the visual system behaves not as a single detector mechanism preceded by a single broadband spatial filter but as a number of independent detector mechanisms each preceded by a relatively narrowband filter 'tuned' to a different frequency...Such a model could account for our findings...”

Translation: Robson and Cambell's (1968) results did not bear out their original predictions, and they speculated as to possible alternative accounts. Between 1968 and 1994, no firmer conclusions were apparently available.

Note also that the analogy between frequency of pressure waves and the “frequency of periodic patterns (gratings)” is very loose. What is being claimed, specifically, is that there is a class of visual neurons that are excited by stimuli with a specific, sine-wave-type luminance structure across a region of space (more specifically, across a region of the retina), and that they are sensitive to the frequency of these spatial luminance alterations. But frequency of pressure waves is a fundamental feature of the energy that interacts with our sensory system to initiate perception. Grating patterns, on the other hand, are just one of an infinite number of possible patterns of light impinging on our retinas. If assumptions about vision are to rest on analogy, then frequency of light waves would seem more appropriate.

Authors: “Do these visual filters participate in everyday tasks such as reading and object recognition?”

Translation: We assume the existence of special, “low-level” mechanisms for detecting grating patterns of light on the retina. (Campbell and Robson, 1968 specified visual angle, i.e. extent on the retina, in defining their patterns). We wonder if these exist exclusively to detect grating patterns, or whether they are engaged in seeing other things as well. We're particularly interested in the perception of familiar objects that we can name upon seeing. The possibility that the visual system may possess “low-level” neurons interested only in ecologically irrelevant grating patterns but not in objects seems to us to be not only credible but testable and worth testing...

Authors: “After all, grating visibility only requires the distinguishing of pattern from blank, whereas object recognition, for example letter identification, requires classification by the observer into one of many learned categories.”

Translation: It's possible that letter identification doesn't implicate mechanisms used for seeing “pattern from blank,” or for seeing unfamiliar letters. To the extent that such mechanisms might, in fact, be implicated in letter recognition, we presume they consist of spatial filters.

Authors: “Here, we make use of results from hearing research (Patterson, 1974).”

Translation: An ad hoc model constructed on the basis of hearing experiments is an appropriate model for testing our conceptually confused variant of an assumption about the visual system based on another analogy to audition. (From Patterson, 1974: From Patterson (1974): “Threshold for a pulsed tone was measured as a function of its distance in frequency from the edge of a broad band of noise with very sharp skirts. Tone frequency was held constant at 0.5, 1.0, 2.0, 4.0, or 8.0 kHz while the position of the noise edge was varied about the frequency of the tone. The spectrum level of the noise was 40 dB. As expected, tone threshold decreased as the distance between the tone and the noise edge increased, and the rate of decrease was inversely related to tone frequency. The data were used in conjunction with a simple model of masking to derive an estimate of the shape of the auditory filter. A mathematical expression was found to describe the filter, and subsequently, this expression was used to predict the results reported by several other investigators.”)

Authors: We find that letter-identification and grating detection filters are identical, showing that the recognition of these objects at one size is mediated and constrained by a single visual filter, or 'channel.'

Translation: Our “single visual filter” conclusions contradict the speculations of Campbell and Robson (1968) (the authors we cited as support for the existence of filters to begin with) i.e. that “we may suppose that the visual system behaves not as a single detector mechanism preceded by a single broadband spatial filter but as a number of independent detector mechanisms each preceded by a relatively narrowband filter 'tuned' to a different frequency.” We don't know if our results on "letters" apply to other shapes. The varied shapes and proportions of "letters" have no bearing on the issue. For the visual system, "letters" is a special category of its own.

Authors: Surprisingly, our noise-masking paradigm shows that the same channel performs both low-level detection of narrow-band gratings and high-level identification of broad-band letters.

Translation: Uncorroborated assumptions inspired by analogies to electrical circuits and sound systems, which ignore the fact of neural inhibition and the principles of perceptual organisation, allowed us to show that hypothetical grating-detectors are responsible for the processes involved not only in perceiving, but also in recognizing letters. (Clearly a breakthrough for memory research as well as perception.) Also, we are arbitrarily splitting the part of the pattern we are showing observers into “noise” and “signal” terms, and assume that the visual system agrees with our analysis and segregates letters from splotches, without recourse to any organizing constraints (e.g. figure-ground rules). (Also, see again comment above re: single channel.)

Authors: (Blurb to Figure 1): Note that changes in viewing distance, from 3 to 60cm, hardly affect the visibility of any given letter, indicating that the channel scales with letter size. (cont'd in next comment).

On 2014 Nov 23, Harri Hemila commented:

A manuscript version of the paper is available at the Helsinki University institutional repository: http://hdl.handle.net/10250/8077

On 2016 May 03, Hugues BEDOUELLE commented:

For an unknown reason, this article is absent from the archives of "Protein Engineering Design and Selection". A pdf file of the article can be found at URL: http://hugues.bedouelle.free.fr

On 2015 Apr 15, Mick Watson commented:

The authors have simply (re)invented integration, a mathematical procedure taught to most high school students. See https://fliptomato.wordpress.com/2007/03/19/medical-researcher-discovers-integration-gets-75-citations/

On 2014 Nov 30, Harri Hemila commented:

Believing that the 2% average effect of vitamin E on mortality is valid for all ATBC participants is an example of ecological fallacy.

The ATBC Study, Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group., 1994 reported that the average mortality in participants administered vitamin E was not different from the non-vitamin E group with RR = 1.02 (95% CI 0.95, 1.09).

However, a subsequent subgroup analysis found that the effect of vitamin E was not uniform over all the ATBC Study participants. The combination of age and dietary vitamin C modified the effect of vitamin E so that there was strong evidence of heterogeneity in the effect of vitamin E over 6 subgroups (P = 0.0005) Hemilä H, 2009. Furthermore, given that baseline age modified the effect of vitamin E, a further analysis by the participants’ follow-up age was done and a significant difference in the effect of vitamin E on mortality was observed before and after the age of 71 years (P = 0.03) Hemilä H, 2011.

Ecological fallacy occurs where data about a group is used to conclude information about an individual. Thus, assuming that the +2% average effect of vitamin E on mortality in the ATBC Study is valid for all ATBC participants is an example of ecological fallacy. A substantial proportion of the ATBC Study participants are inconsistent with the average effect.

On 2017 May 29, Israel Hanukoglu commented:

The DOI address for the article is: http://dx.doi.org/10.1016/0960-0760(94)90266-6

On 2016 Jul 23, Jonathan Eisen commented:

I am posting some notes and other materials relating to this paper on Figshare. See https://figshare.com/account/home#/projects/15032.

On 2014 Oct 26, EDWARD BERRY commented:

The potato hinge protein has a perfect CX9CX3C----CX3CX9C motif which by homology with vertebrate structures should form a helix hairpin with disulfides holding the two arms together. This is the motif recognized by the MIA40/CHCHD4 disulfide relay import system. And like other MIA40 substrates, the hinge protein ends up in the inter-membrane space (attached to cyt c1 of the bc1 complex). I wonder if anyone has checked whether Hinge is imported by the MIA40 system.

In vertebrates one of the middle cysteines is lost, some residues are inserted, spoiling the perfect cannonical MIA40 import sequence. Only two disulfides are formed, and there is a short leader sequence although it is not a typical mitochondrial targeting sequence.

In Saccharomyces, all but two of the cysteines are lost, and the hairpin is clamped by a single disulfide. Could this represent a switch from one import mechanism to another over the course of evolution?

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2014 Sep 20, Dr Yasmin Momin commented:

mucoepidermoid carcinoma of ovary arising in dermoid is a rare case we reported

On 2017 Mar 23, Misha Koksharov commented:

There is a later paper on this topic with important critical comments: Dworak M, 2011

On 2017 May 30, Thomas Heston commented:

The data presented in this study do not support ageism but rather illustrate a primary feature of statistics: as the sample size increases, you are more likely to find a statistically significant p-value. First of all, look at admission rates to the coronary care unit (CCU). If there was a gender bias, then a greater proportion of men (or women) without acute myocardial infarction would be admitted to the CCU compared to the other sex. This study shows clearly that sexism in CCU admission rates is not present. In 1990, 53% of men admitted to the CCU did not have an infarction compared to 52% of women, i.e. over half of the people admitted to the CCU did not have a myocardial infarction yet received CCU level care. This difference is not statistically significant. Then, in 1992 it was found that 48% of men admitted to the CCU did not have infarction compared to 54% of women. This difference was statistically significant, indicating that a greater proportion of women vs men admitted for suspected myocardial infarction received CCU level care. If anything, this represents sexism against men, not against women. But if we look at the data closer, we find that quite a few more people were admitted for suspected infarction in 1992 compared to 1990. This larger sample size means that we are more likely to find statistically significant differences. So while no statistically significant difference was found with the lower sample size (n=1473) in 1990, the higher sample size in 1992 (n=1967) resulted in a statistically significant difference. This is not surprising, this is just how statistical analysis works: large sample sizes are much more likely than small sample sizes to show statistically significant differences. To highlight this further, look at when the authors broke down their data by age (see Table 4). When broken down by age, no significant differences were found, but when all ages were combined, a statistically significant gender difference was found in 1990 and in 1992 in terms of thrombolytic therapy. This does not indicate that the differences are explained by age, but rather indicates that small sample sizes are less likely to show statistically significant differences compared to large sample sizes. The data does show a difference in rate of thrombolysis that is interesting, with an associated difference in mortality rates. My interpretation of this data is that a higher percentage of men vs women with confirmed infarction received thrombolytic therapy, and a lower percentage of men vs women with confirmed infarction died. Unlike the CCU admission rates which are not very illuminating and do clear show gender or age bias, the rate of thrombolysis suggests a bias towards more aggressive treatment of men with infarction (likely starting with differences in their emergency room care Heston TF, 1992). Furthermore, the data also suggest that thrombolysis works, as a lower in-hospital mortality rate was seen for men vs women. However, mortality was not broken down by whether or not the patient had received thrombolysis, so a meaningful analysis of mortality by gender and thrombolytic therapy is not possible.

On 2013 Jun 13, Karl Broman commented:

The idea is obvious in retrospect, but it wasn't at the time; this paper made a big difference.

On 2017 Aug 31, Santosh Kondekar commented:

I request the authors to comment on the link below: https://www.ncbi.nlm.nih.gov/pubmed/511337#cm511337_73741 Please share your experience if you had come across any accidental single heavy dose of amikacin. Thank you.

On 2013 Jun 14, Michael Schatz commented:

This is a seminal paper in genome assembly, precisely defining the unitigging algorithm that forms the basis of all overlap-layout-consensus assemblers since.

On 2016 Jan 04, S A Ostroumov commented:

New theory is formulated: the role of membrane potential as a multi-functional regulator of membrane proteins, in biomembranes of various types.

On 2014 Nov 25, Harri Hemila commented:

A secondary analysis of this study has been published in Hemilä H, 2013, DOI. The secondary analysis calculated that the incidence of all asthma attacks was reduced by RR = 0.22 (95% CI 0.06 to 0.81), and the incidence of severe and moderate asthma attacks was reduced by RR = 0.11 (95% CI 0.02 to 0.48).

On 2015 Apr 02, Harri Hemila commented:

Secondary analyses of Schachter EN, 1982 have been published in Hemilä H, 2013 and Hemilä H, 2014.

On 2014 Aug 08, PubMed Commons Moderator commented:

NCBI system test

On 2014 Jan 08, Brett Snodgrass commented:

Thank you for the excellent article. Please provide your kind attention to the distinction between the Thebesian veins and the vessels of Wearn.

http://bit.ly/Thebesius http://bit.ly/JTWearn

The Thebesian veins may indeed be involved in drainage of the "dye/contrast" into the ventricles. The authors report what is presumably the vessels of Wearn “direct pathways of drainage into the right ventricle from the septal artery.” That depends on the definition of the term “direct.” If it means before the capillary beds, then it is the vessels of Wearn. If it means all connections excluding the coronary sinus, then it may include both the vessels of Wearn and the Thebesian veins.

For additional commentary on the subject, please see the subsequent link. https://twitter.com/BrettSnodgrass1/status/419196829339639808

http://bit.ly/vasaThebesii

Comments or suggestions are welcome.

Thank you very much.

On 2014 Dec 03, Harri Hemila commented:

Fulltext is available at http://jap.physiology.org/content/54/1/208

On 2018 Jan 07, Misha Koksharov commented:

A missing link to the pdf of this paper (on ScienceDirect): https://doi.org/10.1016/0020-711X(83)90066-6

On 2018 Jan 09, Misha Koksharov commented:

A link to pdf (which is missing here): http://dx.doi.org/10.1203/00006450-198010000-00008

On 2014 Nov 23, Harri Hemila commented:

A manuscript version of the paper is available at the Helsinki University institutional repository: http://hdl.handle.net/10250/135149

On 2016 Feb 17, Ben Ewen-Campen commented:

Fascinating!

On 2014 Nov 25, Harri Hemila commented:

A secondary analysis of this study has been published in Hemilä H, 2013. In the tetanus patients aged 1 to 12 years, vitamin C treatment was associated with a 100% reduction in case fatality rate (95% CI from -100% to -94%). In tetanus patients aged 13 to 30 years, vitamin C treatment was associated with a 45% reduction in case fatality rate (95% CI from -69% to -5%).

On 2014 Dec 03, Harri Hemila commented:

Fulltext is available at http://dx.doi.org/10.1016/0262-1746(83)90077-X

On 2014 Oct 28, Harri Hemila commented:

English translation of this paper is available at: http://www.mv.helsinki.fi/home/hemila/T6.pdf

On 2016 Feb 16, Lydia Maniatis commented:

Another example of the problem discussed by Teller can be found in Pelli (1990), who is proposing a model of perception:

"In order to make the model as general as possible, yet still be able to measure its parameters, we need threeassumptions,or constraints. First we assume that the observer's level of performance increases monotonically with the contrast of the signal (when everything else is fixed). This guarantees that there will be a unique threshold. Secondly, as indicated on the diagram by the prefix contrast-invariant we assume that the calculation performed is independent of the contrast of the effective stimulus, which is its immedi- ate input. Together, assumptions 1 and 2 are a linking hypothesis. They imply that the observer's squared contrast threshold (which we can measure) is pro- portional to the effective noise level (which is inaccessible). Thirdly, we assume that the equivalent input noise is independent of the amplitude of the input noise and signal, or at least that it too is contrast- invariant, independent of the contrast of the effective image. These assumptions allow us to use two threshold measurements at different external noise levels to estimate the equivalent noise level. In effect, the assumptions state that the proportionality con- stant and the equivalent noise Neq are indeed constant, independent of the contrast of the effective image. These three assumptions are just enough to allow us to make psychophysical measurements that uniquely determine the parameters of our black-box model. Our model makes several testable predictions, as will be discussed below."

It's worth noting that the main function of the rationale seems to be one of practical convenience.

Theoretically, Pelli (1990) is proposing to make the case that: "the idea of equivalent input noise and a simplify- ing assumption called 'contrast invariance' allow the observer's overall quantum efficiency (as defined by Barlow, 1962a) to be factored into two components: transduction efficiency (called 'quantum efficiency of the eye' by Rose, 1948) and calculation efficiency..."

Although he claims his model makes testable predictions, he also states that they had not, as of publication been tested.

Pelli and Farrell (1999) seem to be referencing the untested, two-component model when they state that: "it is not widely appreciated that visual sensitivity is a product of two factors. By measuring an additional threshold, on a background of visual noise, one can partition visual sensitivity into two compo- nents representing the observer鳠efficiency and equivalent noise. Although they require an extra threshold measurement, these factors turn out to be invariant with respect to many visual parameters and are thus more easily characterized and understood than their product, the traditional contrast threshold."

No references are provided to suggest the proposal has been corroborated. This problem is not remedied by the subsequent statement that: "Previous authors have presented compelling theoreti- cal reasons for isolating these two quantities in order to understand particular aspects of visual function (refs. 3 㠱3)," since all of the references predate the Pelli (1990) claims. Conveniently, the authors "ignore theory, to focus on the empirical properties of the two factors, especially their remarkable invari- ances, which make them more useful than sensitivity"). Ignoring theory unfortunately seems to be a hallmark of modern vision science.

In this way, Pelli papers over a theoretical vacuum via technical elaboration of an untested model.

Both Pelli (1990) and Pelli and Farrell (1999) are referenced by more recent papers as a support for the use of the "Equivalent noise" model.

Pelli (1990) is cited by Solomon, May & Tyler (2016), without a further rationale for adopting the model (I've commented on that article here: https://pubpeer.com/publications/62E7CB814BC0299FBD4726BE07EA69).

Dakin, Bex, Cass and Watt (2009) cite Pelli and Farrell (1999), their rationale being that the model "has been widely used elsewhere."

I feel inclined to describe that what is going on here (it is not uncommon) as a kind of "theory-laundering," where ideas are proposed uncritically, then uncritically repeated, then become popular, and their popularity acts as a substitute for the missing rationale. Is this science?

On 2016 Feb 15, Lydia Maniatis commented:

In reading a number of papers in visual perception, I repeatedly noticed authors using the term "linking hypothesis." "Linking hypotheses" - or assertions about how some experimental effect was linked to some cause -would be "introduced" without any ado, i.e. casually, without a rationale. It seemed as though we were supposed to take these "hypotheses" as givens in the interpretation of data, which didn't seem right. I googled the term "linking hypothesis" looking for some kind of formal definition, but didn't find anything of that kind. I did, however, find this article, which confirmed all my worst suspicions. I've only looked over as yet, but here is the final, jaw-dropping paragraph:

"Perhaps we should include more often in our publications a paragraph or two making our linking propositions explicit. It will be important to define the ranges of intended applicability of individual linking propositions, the kinds of support they receive from prior experiments, their consistency with other broadly accepted linking propositions, the constraints they place on the composite map, the ancil- lary assumptions involved and the overall fit of the linking propositions into the current theoretical net- work of visual science. Within a few years, enough such descriptions should become available that it would be possible to refer to and build upon earlier explications, rather than starting from scratch each time. Similarly, perhaps reviewers could be encouraged to use the explicitness and potential values of linking propositions as one of the criteria of excellence for papers in which arguments containing link- ing propositions are explicitly or implicitly made."

Essentially, this paragraph reveals that, at least as of the time the article was written, vision "scientists" were basing research on arbitrary claims for which they did NOT define ranges of intended applicability; defend with respect to previous research findings; ensure that they were consistent with accepted ideas (or at least how they challenged these); explain their general implications and connection to the current theoretical framework. They were, rather, "starting from scratch" on the basis of arbitrary assertions. This is not a recognisable picture of the scientific method.

It doesn't appear that Teller's hopes for correction of these problems were realised. As I read the literature, the culture of "linking hypotheses" and all that that entails has become normalised. In fact, it may have gotten worse, as it has combined with the fashion for model-fitting in vision science. Thus, data collected is arbitrarily assumed to be "linked" to underlying processes, and the data are fitted to an algorithm, which, due to the high degree of predictability of the general outcomes (e.g. that attention will limit performance) and large number of free parameters, will always be achieved "more or less," without, of course, having general applicability.

I've criticised a number of articles from this unfortunate new (maybe not so new) tradition (a few examples below):

https://pubpeer.com/publications/90941136CC181AFE4896477BF5BB44

https://pubpeer.com/publications/62E7CB814BC0299FBD4726BE07EA69

https://pubpeer.com/publications/F0FDE1805AE5BDE583E3883A8AF39C

A particularly devilish aspect of this approach is that the absence of intellectual/theoretical rigor is masked not only by incoherence but also by mathematics, which may confuse or scare off potential critics. But the same thing applies to math as to computing: Garbage in, garbage out. The rationale is the thing.

On 2014 Nov 30, Harri Hemila commented:

The paper is available at: http://www.mv.helsinki.fi/home/hemila/CP/Hunt_1984_ch.pdf

On 2014 Oct 20, David Mage commented:

This is an excellent review. However, it seems to have overlooked the paper "Neonatal mortality, the male disadvantage" by Naeye RL, Burt LS, Wright DL, Blanc WA, Tatter D, in Pediatrics. 1971 Dec;48(6):902-6, PMID: 5129451, that concluded that the male excess in infant mortality "must" be X-linked. Naeye et al.'s conclusion that an X-linkage is involved has been supported by work following this 1983 paper as shown in the following:

Is excess male infant mortality from sudden infant death syndrome and other respiratory diseases X-linked? Mage DT, Donner EM. Acta Paediatr. 2014 Feb;103(2):188-93. doi: 10.1111/apa.12482. Epub 2013 Dec 20. PMID: 24164639

The X-linkage hypotheses for SIDS and the male excess in infant mortality. Mage DT, Donner M. Med Hypotheses. 2004;62(4):564-7. PMID: 15050108

The fifty percent male excess of infant respiratory mortality. Mage DT, Donner EM. Acta Paediatr. 2004 Sep;93(9):1210-5. PMID: 15384886

A genetic basis for the sudden infant death syndrome sex ratio. Mage DT, Donner M. Med Hypotheses. 1997 Feb;48(2):137-42.PMID: 9076695

Female resistance to hypoxia: does it explain the sex difference in mortality rates? Mage DT, Donner M. J Womens Health (Larchmt). 2006 Jul-Aug;15(6):786-94. Review. PMID: 16910910

On 2015 Jun 15, Salzman Lab Journal Club commented:

This of course is a landmark paper, clearly and concisely demonstrating that RNA alone can catalyze reactions. A finding that is a bit obscure here is that nicked circle IVS has mobility similar to linear IVS minus 15 nt. A later paper by the Cech group showed that this is because the autocyclization reaction cleaves off the 5'-most 15 nt of the linear IVS; they posit that this may limit the reversibility of the splicing reaction. This paper introduced the term "ribozyme", which the authors used in distinction to "enzyme" since the RNA reaction was not multiple-turnover; however these days it has expanded to include any RNA catalysts.

On 2015 Dec 05, S A Ostroumov commented:

Full text online free: Reconstitution of biological molecular generators of electric current. J Biol Chem 251: 7059-7065. https://www.researchgate.net/publication/23071084

On 2013 Oct 29, Jamie Horder commented:

This 1981 report of 5 cases was the first published description of the syndrome that was soon to be known as AIDS. It concluded:

"The above observations suggest the possibility of a cellular-immune dysfunction related to a common exposure that predisposes individuals to opportunistic infections."

On 2017 Jul 25, Richard Sauerheber commented:

We now know that both calcium and magnesium ions at millimolar concentrations decrease the fluidity of biologic membranes. Inside cells, where calcium is at only micromolar concentrations and magnesium at millimolar concentrations, magnesium ion would be involved, particularly since the inner half bilayer phospholipids have negatively charged groups even at slightly acidic pH (6.9) inside cells. The outer half of the bilayer is also susceptible to effects of both calcium and magnesium at millimolar concentrations in extracellular fluid, where phosphate groups on phospholipids would be negatively charged at alkaline pH (7.3) of extracelluluar fluid. The detailed control of the lipid fluidity of membranes in vivo appears to be quite sophisticated.

On 2014 Dec 03, Harri Hemila commented:

Fulltext is available at DOI

On 2017 Jun 09, Israel Hanukoglu commented:

This article is the second in the series of first keratin sequences. The first one, https://www.ncbi.nlm.nih.gov/pubmed/6186381 reported the first sequence of a type I keratin.

This second article reported for the first time the sequence of a type II keratin and predicted the secondary structural domains of the protein by computerized analysis. These predictions were confirmed by an analysis of the crystal structure of a segment of this keratin in coiled-coil form (Lee et al., PMID:22705788).

The coiled-coiled structure of keratins is presented in an article (http://dx.doi.org/10.1002/bmb.20746 ) that also presents a model that can be viewed in Proteopedia.

http://proteopedia.org/wiki/index.php/Keratin

On 2014 Dec 03, Harri Hemila commented:

Fulltext is available at http://dx.doi.org/10.1016/0014-4827(80)90521-2

On 2014 Dec 02, Harri Hemila commented:

Fulltext is available at DOI

On 2014 Dec 03, Harri Hemila commented:

Fulltext is available at DOI

On 2014 Jan 11, Brett Snodgrass commented:

Dear Reader,

Please provide your kind consideration to the following reasons that some of the described "lymphatic structures" may be "myocardial sinusoids."

Quoted from the article: “The subepicardial and subendocardial systems in dogs and pigs communicate via transmyocardial channels” … "in humans these communications have not been identified with certainty." The subendocardial network of lymphatics described in both animals and humans in this study have many similarities to the myocardial sinusoids described by Wearn.

http://bit.ly/JTWearn

Tracing to subepicardial lymphatics was possible in dogs/pigs, but not in humans. This may be explained by the hypothesis that some of the observed “lymphatics” in both animals and humans were “myocardial sinusoids.” Caution should be exercised before assuming that all the irregular subendocardial channels reported in this study were lymphatics. Presumably, many of them were myocardial sinusoids and not lymphatics.

Whether these myocardial sinusoids communicate with subendocardial lymphatics may be a reasonable area for further study.

My opinion is that accurate anatomic terminology is a basic principle underlying good medical science, and I ask others to consider whether the aforementioned definitions are appropriate. If this comment is not helpful, please let me know how it might be improved. Comments and suggestions are welcome.

Thank you very much.

On 2014 Jan 07, Brett Snodgrass commented:

Dear Reader,

Please see an annotated image from the article. https://twitter.com/BrettSnodgrass1/status/419272033118085120

Comments and suggestions are welcome.

Thank you kindly.

On 2014 Oct 28, Harri Hemila commented:

English translation of this paper is available at: http://www.mv.helsinki.fi/home/hemila/T4.pdf

On 2014 Dec 05, Harri Hemila commented:

English translation is available at: http://www.mv.helsinki.fi/home/hemila/T5.pdf

On 2014 Jan 08, Brett Snodgrass commented:

Thank you for the excellent article.

The authors write “intramyocardial channels normally joining the coronary arteries to the ventricular chambers.” Wearn described these ventriculocoronary arterial connections in addition to atriocoronary arterial connections. The eponym and only pronoun applied to these connections is the vessels of Wearn.

http://bit.ly/JTWearn

Finegold et al. astutely acknowledged the vessels of Wearn (connections) as a possible etiology for their findings. For further information related to PAIVS and the connections, please see:

http://www.ncbi.nlm.nih.gov/pubmed/23332812 https://twitter.com/BrettSnodgrass1/status/419317173689909248

Comments or suggestions are welcome.

Thank you kindly.

On 2017 Aug 31, Santosh Kondekar commented:

Though amikacin is known to be toxic at non therapeutic doses; I feel the toxicity with single high dose is questionable.

A fourteen month old child of a hospital staff nurse had presented to us with loose motions. Injection amikacin was advised along with routine supportive therapy for hydration. The dose of amikacin was advised as 7.5mg/kg/dose. The child had oliguria since last 12 hours. The amikacin injection was supposed to be kept on hold in view of same. Due to some miscommunication and advise being followed by a junior staff nurse and being unsuperwised; the child received an accidental overdose of intravenous amikacin bolus as 750 mg instead of 75.0 mg. The mishap was immediately noted by the mother. Mother being a staff nurse alerted the consultant and nephrologist. Immediately, blood was collected for renal profile, blood gas and amikacin levels. There was no acidosis on ABG and BUN was 24g/dl and Cr was 0.9. The child showed no worsening of symptoms nor any new symptoms like irritability,cry or seizures. A collective decision of consultant and parents was made to wait and watch. parents were informed all toxicities of amikacin in details. Child passed urine in subsequent hour. A repeat renal profile was sent after 6 hours and 24 hours. BUN was 22 and Serum Creatinine was 0.8. An audiometry was done after three months. A decision to perform dialysis was averted. Serum amikacin levels couldnot be done.

I do feel that; in normal renal profile, an accidental overdose upto ten times therapeutic dose in a child should not be a reason to panic and an apprehensive decision to perform hemodialysis can be avoided.

On 2015 Dec 05, S A Ostroumov commented:

Full text online free : Electrogenesis by bacteriorhodopsin incorporated in a planar phospholipid membrane. https://www.researchgate.net/publication/18316493

On 2014 Nov 25, Harri Hemila commented:

A secondary analysis of this study has been published in Hemilä H, 2008, which is available also as a manuscript version, Handle. There is statistically highly significant interaction between gender and vitamin C effect on common cold incidence (P = 0.0001), so that vitamin C reduced cold incidence in males with RR = 0.63 (95% CI 0.50 to 0.78), but not in females (95% CI 0.95 to 1.61).

On 2014 Mar 19, Nigam Shah commented:

The first paper to propose the idea of building a cohort of 'patients like mine'.

On 2015 Dec 11, Harri Hemila commented:

Translation available at: http://www.mv.helsinki.fi/home/hemila/T11.pdf

On 2014 Jan 07, Brett Snodgrass commented:

Excellent question: What Has Happened To The Myocardial Sinusoids? http://www.ncbi.nlm.nih.gov/pubmed/444059/ See http://bit.ly/JTWearn

https://twitter.com/BrettSnodgrass1/status/420517248508252160

Comments or suggestions welcome. Thank you.

On 2015 Jun 02, thomas samaras commented:

Additional information on height, CHD, and longevity is available from these recent publications.

Samaras TT. Shorter height is related to lower cardiovascular disease risk—A narrative review. Indian Heart Journal 2013; 65: 66-71.

Samaras, TT. Is short height really a risk factor for coronary heart disease and stroke mortality? A review. Med Sci Monit 2004; 10(4): RA63-76.

Samaras TT. Evidence from eight different types of studies showing that smaller body size is related to greater longevity. Journal of Scientific Research & Reports. 2014: 3 (16): 2150-2160, 2014; article no. JSRR.2014.16.003.

Samaras TT. Human Scaling and Body Mass Index. In: Samaras TT (ed): Human Body Size and the Laws of Scaling: Physiological Performance, Growth, Longevity and Ecological Ramifications. New York: Nova Science Pub; 2007: pp 17-32.

He Q, Morris BJ, Grove JS, Petrovitch H, Ross W, Masaki KH, et al. Shorter men live longer: Association of height with longevity and FOXO3 genotype in American men of Japanese ancestry. Plos ONE 9(5): e94385. doi:10.1371/journal.pone.0094385.

Salaris L, Poulain M, Samaras TT. Height and survival at older ages among men born in an inland village in Sardinia (Italy), 1866-2006. Biodemography and Social Biology, 58:1, 1-13.

Bartke A. Healthy Aging: Is Smaller better? A mini-review. Gerontology 2012; 58:337-43.

On 2018 Jan 31, Denise N Slenter commented:

The pathway outlined in Figure 1, is available as free machine readable data in WP4210 in WikiPathways: https://www.wikipathways.org/index.php/Pathway:WP4210 . This pathway can be used for data analysis with e.g. Pathvisio and Cytoscape!

On 2014 Dec 03, Harri Hemila commented:

Fulltext is available at DOI

On 2015 Dec 05, S A Ostroumov commented:

Full text online free: https://www.researchgate.net/publication/19019216

On 2014 Jun 25, Jacques Barbet commented:

This is an incredibly useful paper to calculate multiple equilibria in solution based on the mass action law.

The method uses a partition function that should be used to teach students.

On 2014 Jul 03, Arnaud Chiolero MD PhD commented:

A must-read in public health

On 2017 Jul 27, Richard Sauerheber commented:

(from the author) Many have argued that insulin stimulates glucose transport in sensitive cells by recruiting already pre-synthesized glucose transport molecules that are inside the cell waiting to be inserted after insulin binds to cell surface receptors. This however would be an energy-requiring and relatively slow process, to insert water soluble transport protein sections through the hydrophobic lipid bilayer. The function of insulin is to conserve energy after eating a meal, storing glucose for future energy needs in the form of glycogen, as well as other foodstuffs, and to quickly react to meal eating, and then to quickly deactivate energy storage between meals. So energy use, such as that required to insert transporters into an already-formed membrane would be wasteful and a contradiction in function. Also, the insulin stimulation of glucose transport is very rapid, finished within a minute, and the reverse, the deactivation of the transport rate, occurs quickly after insulin washes away, as when insulin levels are miniscule between meals. Removal of transporters from a membrane, to be stored inside the cell for later use again when the next meal is consumed, is a cumbersome notion. The data here point to a much more sophisticated and efficient design, where allosteric conformational changes can cause rapid activation and deactivation cycles in transporter activity when insulin is present and then absent, as during and then between meals throughout the day in the in vivo setting. For all the published data suggesting to investigators this is not a proper view, understand that such presented evidence is not compelling or beyond reasonable doubt, including microscopic observations of what are thought to be widespread intracellular transporters waiting for repeated, rapid re-insertion into, and re-removal from, the plasma membrane. The view described here caused my NIH grant renewal in the 1980's to be rejected. My research position eventually was terminated and I went into teaching (which I fortunately dearly love). Meanwhile, I stand by these observations and continue to teach them.

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2014 Aug 09, Matthew Katz commented:

This is a seminal article in cancer care. NSABP B-06 demonstrated the safety of organ-preserving surgery in breast cancer and established a role for radiation therapy in early breast cancer. At the time there were questions about whether radiation was even necessary, but the segmental mastectomy alone arm fared worse. There results have held up at 20 years, also published the NEJM. Fisher B, 2002

We still have more to refine on patient selection, treatment approach and other factors. But NSABP B-06 remains an example of how clinical trials can give patients treatment options without compromising cure rates.

On 2015 Jan 21, David Keller commented:

Vitamin C was administered orally in this study

When vitamin C is ingested orally, the serum concentration is regulated to a maximum of about 300 microM/L. Intravenous administration of vitamin C bypasses enteric control mechanisms, allowing plasma concentrations of up to 20,000 microM/L to be achieved. Alternative practitioners claim special benefits at the supra-physiologic concentrations which can only be achieved with IV administration. This comment is not meant to support or dispute their claims, it is placed here for the reference of researchers who do not have access to the NEJM archives, since the route of administration is not mentioned in the PubMed abstract.

On 2016 Jan 04, S A Ostroumov commented:

Keywords (additional): Halobacterium halobium, Rhodospirillum rubrum, membrane potential, bioenergetics, bacterial photosynthesis,

On 2016 Jan 04, S A Ostroumov commented:

ABSTRACT: A unique short review of innovative landmark articles that discovered and proved the membrane potential across the membranes of the bacteria that use light as a source of energy, namely, the bacteria with traditional type of photosynthesis with bacteriochlorophyll and the bacteria with a new type of energetics that is based on bacteriorhodopsin.

On 2015 Dec 10, S A Ostroumov commented:

Abstract is available, as well as the list of cited publications: https://www.researchgate.net/publication/22754808

On 2013 Nov 24, John Sotos commented:

In a recent letter to the Journal Guarino describes an apparently novel method of detecting ascites: the diaphragm of the stethoscope is placed just superior to the pubic crest of a patient who has been standing for three minutes or more, and the physician determines by auscultation the level where the timbre of the “finger-flicking” percussion note changes from dull to loud (1). A similar technique, alas, was described in the 1930s by two French physicians (2) (3). Without mentioning the three-minute caveat, they found that if the physician auscultated in the iliac fossa of a standing patient with ascites, and percussed the abdomen from superior to inferior, the percussion note had a brusque augmentation at the top of the zone liquidienne (2).

More interestingly, however, the thrust of their articles is directed at a technique they considered far more sensitive and convenient in detecting ascites: listening with the stethoscope bell in one iliac fossa while percussing the contralateral fossa with a “finger pulled back like a hammer” (doigt recourbé en marteau) (3). The presence of ascites is indicated by a distinctive double note in response to percussion (le double bruit ascitique), whereas a single note is heard in normal patients. Abdominal distention due to large ovarian cysts (3) or “enormous urinary retention” (2), the authors say, yields a single sound, while, in cases of hydatidiform cyst, a second sound is present, but of a different character (l’echo hydatique) (2). The authors further claim that, with the patient standing, their method is capable of demonstrating ascites of volume small enough to have otherwise escaped clinical detection. We have ourselves heard the ascitic double note, which the French authors considered the sonic manifestation of a fluid wave (3).

Two hundred years ago, Marie Antoinette’s milliner is reported to have said, “There is nothing new except what is forgotten” (4). The advent of computer-based bibliographic retrieval systems has dramatically improved mankind’s scientific “memory,” but has not perfected it. Thus, there still is (and, most likely, always will be) a vast corpus of pre-electronic knowledge, searchable only by means that are both painful and tedious. Unfortunately, when dealing with an art as ancient as the physical examination, the scrutiny of this literature demands added attention (5).

John G. Sotos, MD

Iredell W. Iglehart III, MD

(1) Guarino JR. Auscultatory percussion to detect ascites. N Engl J Med. 1986 Dec 11;315(24):1555-6. Pubmed 3785320

(2) Lian C, Odinet J. De l’existence d’un double bruit par la percussion abdominale dans l’ascite. Societé Medicale des Hospitaux de Paris. 1931; 55: 1402-1408.

(3) Lian C, Odinet J. Le double bruit ascitique et le signe de la matité horizontale dans la station debout. Presse Medicale. 1934; 42: 1337-1338.

(4) Bartlett J (comp.). Familiar Quotations. 13th ed. Boston: Little, Brown, 1955; 1002.

(5) Sotos JG. Diagnosis of fractures of the hip and pelvis (continued). N Engl J Med. 1983 Apr 21;308(16):971. Pubmed 6835304

On 2013 Jun 19, Robert Tibshirani commented:

This paper, along with

Kung-Yee Liang and Scott Zeger (1986). "Longitudinal data analysis using generalized linear models". Biometrika 73 (1): 13–22.

introduced the Generalized Estimating equation (GEE) approach for modelling repeated or grouped observations. Full probability models for such data are often hard to specify, so GEEs finesse the issue by including a within subject or group correlation matrix in the usual score equations for a generalized linear model. The GEE is an important advance that has had much impact on statistical practice.

On 2017 Jan 27, Guillaume Filion commented:

This study reports that the sex-determining factor is the transcription factor ZFY. The claims were later shown to be erroneous and the sex-determining factor was identified as the transcription factor SRY (https://www.ncbi.nlm.nih.gov/pubmed/1695712). Expressing SRY in the XX mouse "Randy" made it develop as a phenotypic male (https://www.ncbi.nlm.nih.gov/pubmed/2030730), confirming that SRY is indeed the sex-determining factor. A historical summary of the events was published 25 years after the birth of Randy (https://www.ncbi.nlm.nih.gov/pubmed/27190031).

On 2014 Nov 23, Harri Hemila commented:

A manuscript version of the paper is available at the Helsinki University institutional repository: http://hdl.handle.net/10250/135150

On 2014 Jan 08, Brett Snodgrass commented:

Dear Reader,

These diffuse (minute, aka fine) connections may be consistent with the vessels of Wearn. Since we cannot definitively exclude an arteriosinusoidal vessel, using the term "vessels of Wearn" is appropriate.

It is also possible that some of the connections enter the capillary bed before entering the heart chamber. If that is the case, then it is possible that some of the connections are Thebesian connections.

For serial histologic sections, Wearn studied the arteriosinusoidal and arterioluminal vessels utilizing cold celloidin that was too thick to enter the capillaries. Wearn did note that when India ink was injected into the coronary arteries it would enter the heart chambers through numerous minute connections. Since, the ink would not permit serial histologic sections with 3D reconstruction as was used for the arteriosinusoidal and arterioluminal vessels, we may not have sufficient information to specify whether the connections are Arterio-capillary-cameral, or Arterio-capillary-venule-cameral (The venule-cameral connection would be a Thebesian vein).

Thus, when the diffuse connections are identified, we do not have sufficient data to determine whether they are arteriosinusoidal only, or whether some are arteriosinusoidal and some enter the capillary bed before entering the heart chamber. In addition, if some of the connections were arterioluminal vessels, then we would have an even more difficult time naming the radiographic finding. Thus, the term vessel of Wearn has been proposed. For additional commentary, please see. https://twitter.com/BrettSnodgrass1/status/404825015771619328 and https://twitter.com/BrettSnodgrass1/status/413860163033247744

Comments, disagreements, and suggestions are welcome.

Thank you kindly.

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2014 Jan 08, Brett Snodgrass commented:

Dear Reader,

Please consider that approximately 37 years after Wearn's distinguished Harvey lecture, the arterioluminal and arteriosinusoidal vessels (vessels of Wearn), are reported as veins.

Morphological and Functional Alterations of the Coronary Circulation. Harvey Lecture, 1940 - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933738/

Annotations, commentary, and links to additional related references are found at the following Twitter link:

https://twitter.com/BrettSnodgrass1/status/419530221927141376

Comments and suggestions are welcome.

Thank you kindly.

On 2013 Jun 18, Jill Barnholz-Sloan commented:

One of the seminal papers in population stratification bias and admixture effects. This paper was one of the first to describe individual admixture testing and its potential effects and linkage disequilibrium.

On 2015 Dec 11, Harri Hemila commented:

Available at DOI

On 2014 Nov 24, Guillaume Filion commented:

For a retrospective of the ideas behind BALST together with some comments by David Lipman, you can check out the blog post "Once upon a BLAST" at the following link. http://blog.thegrandlocus.com/2014/06/once-upon-a-blast

On 2018 Feb 02, Jim Woodgett commented:

Probably shouldn't comment on a co-authored paper, but I regrettably missed this Drosophila homologue of ZesteWhite3/Shaggy that is involved in fruitfly male fertility and has the (great) name mojoless: https://www.ncbi.nlm.nih.gov/pubmed/17179138

On 2018 Jan 31, Varshil Mehta commented:

If there are any new treatment options available, please mail me on varshil91@gmail.com, since we are actively trying to find new therapies as the older ones are getting exhaustive. Regards, Varshil Mehta

On 2018 Jan 31, Natalie Clairoux commented:

Free version of this article available at http://hdl.handle.net/1866/19710