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  1. Jul 2018
    1. On 2017 Jun 21, Gary Goldman commented:

      It is well established that in Japan, where only 1 in 5 children received varicella vaccination, that those vaccinated maintained protective immunity for 20 years. This was largely due to the vacinees' receiving exogenous exposures to children with natural or wild-type varicella that boosted cell-mediated immunity to varicella zoster virus. During the majority of the study by Kuter et al., varicella vaccine receipients were likewise being boosted through exposure to individuals with wild-type varicella--especially during annual epidemics of varicella. This had the effect of artifically elevating vaccine effectiveness because of the shedding of varicella zoster virus in the community. In communities with widespread varicella vaccination, once oppotunities for exogenous boosts became rare, single-dose varicella vaccination efficacy declined to less than 50% five years after vaccination.Goldman GS, 2005


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    1. On 2013 Nov 24, John Sotos commented:

      Dr. Schwartz dates the first description of hemoglobinuria (as black urine) to the 13th century AD (1).

      About 400 BC, however, Hippocrates described urinary quantity, color, consistency, or sediment in 41 of 42 case reports in his Book of Epidemics (2). Twelve case reports mention black urine, a frequency so high that one wonders if glucose-6-phosphate dehydrogenase deficiency (3) and/or fava bean ingestion could have predisposed this population to hemolysis.

      Inspection of the urine was important in ancient Greek medicine, but has been recently dismissed as “mostly nonsense” (4). Yet, the approach taken by Hippocrates was remarkably modern. In several patients having pigmented urine, Hippocrates checked for the appearance of a sediment after allowing the urine to sit — a maneuver that would have allowed him to distinguish hematuria from hemoglobinuria and myoglobinuria.

      Such insights from Hippocrates are not surprising. As Garrison has remarked, “All that a man of genius could do for internal medicine, with no other instrument of precision than his own open mind and keen senses, he accomplished” (5).

      (1) Schwartz RS. Black mornings, yellow sunsets — a day with paroxysmal nocturnal hemoglobinuria. N Engl J Med. 2004;350:537-538.

      (2) Adams F. The Genuine Works of Hippocrates. Huntington, NY: Robert E. Krieger, 1972; 110-141.

      (3) Tran TH, Day NP, Ly VC, Nguyen TH, Pham PL, Nguyen HP, Bethell DB, Dihn XS, Tran TH, White NJ. Blackwater fever in southern Vietnam: a prospective descriptive study of 50 cases. Clin Infect Dis. 1996;23:1274-1281.

      (4) Majno G. The Healing Hand: Man and Wound in the Ancient World. Cambridge, MA: Harvard University Press, 197; 494 note 159.

      (5) Garrison FH. An Introduction to the History of Medicine. 4th ed. Philadelphia: WB Saunders, 1929: 94.


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    1. On 2017 Jun 08, Egon Willighagen commented:

      Happy to see the PubMed record was updated :)


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    2. On 2017 Feb 13, Egon Willighagen commented:

      The correct DOI is 10.1042/bst0320083


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    1. On 2014 Oct 19, David Mage commented:

      The authors have done an outstanding and excellent study. However, they seem to have failed to notice here that, in Table 2, their reported male fraction of SIDS (0.612) in 260 cases (excluding matched sets) is identical to the male fraction of SIDS reported by Mage and Donner (PMID 9076695) of 41,238 male and 26,140 female in 36 SIDS data sets giving a male fraction of 0.6120. This is important to note because the consistancy of the male fraction of SIDS throughout time and among various countries supports a recessive X-linkage of susceptibility to SIDS that seems to be ignored inspite of the early conclusion of Naeye et al. in PMID 5129451, that male susceptibility to infant death "must" be X-linked.


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    1. 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


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    1. 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


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    1. On 2015 Jun 02, thomas samaras commented:

      Additional information on birthweight, 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.


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    1. On 2014 Feb 05, Tom Kindlon commented:

      A CFS study which raises questions about the use of the Role Emotional (RE) subscale of the SF-36 to define CFS

      (This was originally posted here: http://www.biomedcentral.com/1472-6963/3/25/comments but the formatting has been lost and some people may read the paper on PubMed Central)

      As I mentioned in the previous comment, this paper recommends, amongst other questionnaires, the use of the SF-36 questionnaire but does not specify which subscales should be used.

      One group of researchers[1] have decided to use the physical function, role physical, social function and role emotional subscales of the SF-36 to define disability, with a low score on just one of these subscales being sufficient to satisfy the criteria (i.e. there didn't need to be more than one low scores).

      Since then, this definition has gone on to be used in numerous papers (such as [2-5]) as the CDC are using it as the definition they're using for their CFS studies in the US, and they probably have the largest CFS research program in the world. It was used to give the prevalence rate of 2.54% for CFS in the adult population[6]. Most recently, it was used to investigate the prevalence of the reporting of childhoold trauma in this cohort[7].

      A study by Fulcher and White (2000)[8] raises questions about the use of the Role Emotional (RE) subscale of the SF-36 to select patients with CFS. The study involved 66 patients with CFS without a current psychiatric disorder, 30 healthy but sedentary controls, and 15 patients with a current major depressive disorder.

      It found, amongst other things, that "the two patient groups were significantly more incapacitated than the sedentary controls on all SF-36 measures (p<0.001), except that the patients with CFS were not significantly different in emotional or mental function." Also, "the depressed subjects were significantly more incapacitated in emotional and mental functioning than the patients with CFS p<0.001)."

      These results suggest that low scores on the emotional and mental functioning subscales of the SF-36 do not seem to be an intrinsic part of CFS (if they're found, they could be related to comorbid psychiatric issues). They also points out the risks of using the RE subscale alone [especially given CFS shares some characteristics with depression and so some people with depression (but not CFS) could potentially score the required 25 points on the Symptom Inventory] i.e. one could inadvertently include some people who have depression but not CFS, as CFS patients.

      References

      [1] Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C. Chronic Fatigue Syndrome – A clinically empirical approach to its definition and study. BMC Medicine 2005, 3:19<br><br>

      [2] Raison CL, Lin JM, Reeves WC. Association of peripheral inflammatory markers with chronic fatigue in a population-based sample. Brain Behav Immun. 2008 Dec 11.

      [3] Welberg LA, Capuron L, Miller AH, Pagnoni G, Reeves WC. Neuropsychological performance in persons with chronic fatigue syndrome: results from a population-based study.Majer M, Psychosom Med. 2008 Sep;70(7):829-36.

      [4] Nater UM, Youngblood LS, Jones JF, Unger ER, Miller AH, Reeves WC, Heim C. Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome. Psychosom Med. 2008 Apr;70(3):298-305.

      [5] Nater UM, Maloney E, Boneva RS, Gurbaxani BM, Lin JM, Jones JF, Reeves WC, Heim C. Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls. J Clin Endocrinol Metab. 2008 Mar;93(3):703-9.

      [6] Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Popul Health Metr. 2007 Jun 8;5:5.

      [7] Heim C, Nater UM, Maloney E, Boneva R, Jones JF, Reeves WC. Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction. Arch Gen Psychiatry. 2009 Jan;66(1):72-80.

      [8] Fulcher KY, White PD. Strength and physiological response to exercise in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 2000 Sep;69(3):302-7.


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    2. On 2014 Feb 03, Tom Kindlon commented:

      Which subscales of the SF-36 should be used? Results from a study in Fibromyalgia patients

      (This was originally posted here: http://www.biomedcentral.com/1472-6963/3/25/comments but the formatting has been lost and some people may read the paper on PubMed Central)

      This paper recommends, amongst other questionnaires, the use of the SF-36 questionnaire. But which subscales should be used? One group of researchers[1] decided to use the physical function, role physical, social function and role emotional subscales of the SF-36 to define disability, with a low score on just one of these subscales being sufficient to satisfy the criteria (i.e. there didn't need to be more than one low scores). Since then, this definition[1] has gone on to be used in numerous papers (for example, 2-5).

      But is this a good way of using the SF-36 given the Fukuda definition for CFS[6] requires that there be a "substantial reduction in previous levels of occupational, educational, social, or personal activities".

      Fibromyalgia patients share many similarities with CFS patients and many researchers use CFS and FMS patients together in their studies (for example [7-10]).

      One study[11] recently assessed Fibromyalgia Syndrome (FS) patients using the SF-36 questionnaire. It found that patients could be broken down into two groups using the SF-36 subscales looking at mental well-being (social functioning, role limitation due to emotional health problems, and mental health). "One group demonstrated psychological dysfunction, whereas the other showed normal psychological scores. Physical well-being scores (physical functioning, role limitation due to physical health problems, bodily pain, general health, and vitality) did not differ between FS patients but were altogether below the normal range."

      If this was found to be the same in other populations, it would suggest that perhaps including patients who solely have low scores on subscales assessing mental well-being such as the role emotional and social functioning subscales of SF-36, which is all the CFS definition prepared by Reeves[1] requires, would select a group of people with psychological dysfunction but not necessarily greater physical disability.

      References:

      [1] Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C. Chronic Fatigue Syndrome – A clinically empirical approach to its definition and study. BMC Medicine 2005, 3:19

      [2] Reeves WC, Heim C, Maloney EM, Youngblood LS, Unger ER, Decker MJ, Jones JF, Rye DB. Sleep characteristics of persons with chronic fatigue syndrome and non-fatigued controls: results from a population-based study. BMC Neurology 2006, 6:41

      [3] Majer M, Jones JF, Unger ER, Youngblood LS, Decker MJ, Gurbaxani B, Heim C, Reeves WC. Perception versus polysomnographic assessment of sleep in CFS and non-fatigued control subjects: results from a population-based study. BMC Neurology 2007, 7:40

      [4] Jones JF, Maloney EM, Boneva RS, Jones AB, Reeves WC. Complementary and alternative medical therapy utilization by people with chronic fatiguing illnesses in the United States. BMC Complementary and Alternative Medicine 2007, 7:12

      [5] Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R.Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Popul Health Metr. 2007 Jun 8;5:5.

      [6] Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A: The chronic fatigue syndrome; a comprehensive approach to its definition and study. Ann Int Med 1994, 121:953-959.

      [7] Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006 Nov;12(9):857-62.

      [8] Glass JM. Cognitive dysfunction in fibromyalgia and chronic fatigue syndrome: new trends and future directions. Curr Rheumatol Rep. 2006 Dec;8(6):425-9.

      [9] Zachrisson O, Regland B, Jahreskog M, Jonsson M, Kron M, Gottfries CG. Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome--a randomised controlled trial. Eur J Pain. 2002;6(6):455-66.

      [10] Zachrisson O, Regland B, Jahreskog M, Kron M, Gottfries CG. A rating scale for fibromyalgia and chronic fatigue syndrome (the FibroFatigue scale). J Psychosom Res. 2002 Jun;52(6):501-9.

      [11] Oswald J, Salemi S, Michel BA, Sprott H. Use of the Short-Form-36 Health Survey to detect a subgroup of fibromyalgia patients with psychological dysfunction. Clin Rheumatol. 2008 Apr 1


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    1. On 2015 Nov 25, S A Ostroumov commented:

      I have studied this species of plants also. It was also a factor to remove some metals from water. It is a useful paper, congratulations to the authors!


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    1. On 2013 Oct 28, DAVID SANDERS commented:

      See the earlier articles "Sulfhydryl involvement in fusion mechanisms" [2000]Sanders DA, 2000 and "Ancient viruses in the fight against HIV" [2003] Sanders DA, 2003 for the prediction of the results published here.


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    1. On 2014 Nov 02, Ivan Oransky commented:

      The first author of this paper, which was retracted in 2007, was found by the Office of Research Integrity to have falsely manipulated images: http://retractionwatch.com/2014/10/31/former-nih-lab-director-faked-findings-in-three-papers-ori/


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    1. On 2017 Apr 23, Md. Shahidul Islam commented:

      In human beta cells TRPM5 is almost absent while its closest relative TRPM4 is abundant. Marabita F, and Islam MS. Pancreas. 2017 Jan;46(1):97-101. Expression of Transient Receptor Potential Channels in the Purified Human Pancreatic β-Cells. PMID: 27464700 DOI: 10.1097/MPA.0000000000000685


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    1. On 2016 Aug 30, Stephen Strum commented:

      This is an excellent article providing an in-depth review of c-Met and its relation to hepatocyte growth factor (HGF). Authors discuss various targets of therapy (TOT) involving this receptor (c-Met) + ligand (HGF) pathway. I highly recommend spending the time to read this article.


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    1. On 2015 Dec 02, S A Ostroumov commented:

      This article was among TOP FULL-TEXT DOWNLOADS in 2014-2015. 67 downloads from ResearchGate, 669 views, 9 bookmarks by 26.01.2015. Full text online free: https://www.researchgate.net/publication/200594244; Full title of the journal: Rivista di Biologia / Biology Forum. 2003 (May). 96: 327-332. Abstracts in Eng. and Italian (p. 332).

      Additional KEY WORDS: priorities, fundamentals, environmental sciences, biospheric sciences, life sciences, biomedical sciences, geosciences, ecosystems, biosphere, organisms, levels of life systems, man-made impact, anthropogenic, effects, terrestrial, aquatic, research topics;


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    1. On 2013 Jul 17, Toby Gibson commented:

      Chk1 is an important DNA damage checkpoint protein kinase. Biochemical evidence suggests that the sites most vigorously phosphorylated by the Chk1/2 kinases match or are close to the pattern (LF)xRxx(pST)(LF). See, for example, these articles (PMID: 10648819; 10761933; 11821419; 12711320). If only one of the three specificity determining positions are lost, the kinases may still phosphorylate, but at reduced activity. This gradation in activity might have biological significance and also means that it is difficult to define motif patterns for Chk kinase substrate sites. Currently we are trying to do this for the ELM protein motif resource (http://elm.eu.org/).

      In the paper that I would like to comment on here, the reported phosphorylation site at Ser47 of p73 - VgGtd(pS)S - lacks all of the strong specificity determinants (capitalised positions). It has been confounding our attempt to define a Chk phosphorylation site pattern for ELM. However, based on a close examination of the figures in the paper, we have now decided to exclude this p73 site from further consideration.

      The MCB paper is open access and high resolution figures are available at both the MCB site and through PubMed.

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC262369/figure/f2/

      Fig. 2A lower left gel. Lanes 3-4 are the same as lanes 5-6. Note also the inconsistent gap length between band pairs. This gel appears to be a bounded grey box into which band pairs have been pasted.

      Fig. 2B upper left gel. This appears to be a bounded grey box in which the + lanes have been pasted in. These have vertical edges that do not correspond to the edges of the bands. The - lanes are just smooth, grey blanks.

      Fig. 2B lower left gel. The band in lane 4 is the same as in lane 5. Associated dots and shadows are diagnostic despite a slight size difference.

      Fig. 2B lower right gel. This is a bounded grey box into which three bands have been pasted. The band in lane 1 has been pasted over the edge line! The band in lane 3 has also been pasted over the edge line!

      Fig. 2C Lower left gel. The band in lane 2 has been pasted over the edge line! This is another grey box into which bands have been pasted.

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC262369/figure/f3/

      Fig. 3A upper gel. Bands in lanes 1-4, 6-7, 10 are identical. Maximum resolution is required to see this unambiguously.

      Fig. 3B upper gel. Bands in lanes 4, 6, 9-10 are identical. Maximum resolution is required to see this.

      Fig. 3B middle gel. Bands in lanes 2,4 and probably 3 are the same. Bands in lanes 6,7,9 are the same.

      Fig. 3D upper right gel slice. All eight bands are identical. Maximum resolution is required to see this (it is not clear from the pdf download of the whole paper). Also these bands might be elongated versions of the reused bands listed for Fig. 3A.

      Fig. 3 D lower left gel slice. Lanes 2-7 are identical to lanes labelled 8-13 of the lower right gel slice. According to the labelling above each lane, these are certainly to be understood as different experiments.

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC262369/figure/f4/

      Fig. 4A Upper right slice. Band pair in lanes 1-2 are the same as 7-8. Band in lane 4 is the same as band in lane 6.

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC262369/figure/f5/

      Fig. 5D lower panel. Bands 1-3 are the same as bands 6-8, except that they are the mirror image.

      The paper is ten years old. Therefore it is unlikely that the raw data used to assemble these figures still exists, though it would be fascinating to make comparisons if any original data can be found.


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    1. On 2017 Aug 05, Fernando Castro-Chavez commented:

      Dear Reader, This is where it all started, when I moved from Mexico to the U.S., at the Baylor College of Medicine (BCM), within the Texas Medical Center; we had Perilipin knock out mice able to eat as much fat and carbohydrates as they wanted, never getting obese, but remaining slender, so, we were able to determine the basic biochemical profile of these organisms, which had over expressed the pathways of Beta Oxidation, and of the Respiratory Chain, and also of the Krebs Cycle, while they had down regulated the pathways of the Unsaturation of Fats, and of the production of Cholesterol. Sincerely, Fernando Castro-Chavez.


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    1. On 2013 Nov 24, John Sotos commented:

      The discussion of how to manage Mrs. P, a 60 year old woman with atrial fibrillation (1), nicely reprised Sir William Osler’s 1907 advice: “Too much stress should not be laid upon arrhythmia per se in the absence of organic disease” (2).

      As presented, however, Mrs. P’s evaluation did not adequately exclude organic disease: neither her body mass index nor a general description of her habitus was provided. Although her physicians obviously had access to this information, its omission from the case record suggests that an emerging correlate of atrial fibrillation, obstructive sleep apnea (OSA), was not considered as a potential exacerbating factor in her illness.

      The prevalence of OSA in American adults is estimated as 20%, most of it undiagnosed, and most of it related to obesity (3). Hypothyroidism and alcohol ingestion, both of which Mrs. P had, are two of several additional risk factors.

      As recently reviewed in JAMA, the role of OSA in cardiac disorders is receiving increasing attention, in part because OSA “frequently coexists undiagnosed in patients with cardiovascular disease” (4). Several physiological mechanisms plausibly link OSA and atrial fibrillation (4), but few studies have examined their clinical links. Of highest relevance for Mrs. P, however, Kanagala et al (5) found that untreated sleep apnea doubles the likelihood of atrial fibrillation recurring within 12 months of cardioversion, when compared to OSA patients receiving positive pressure treatment.

      The effectiveness, and, therefore, cost-effectiveness, of testing for OSA in patients with atrial fibrillation is unknown. However, given that OSA is itself common, serious, and treatable, a case can be made for testing patients such as Mrs. P for sleep apnea, especially if they are obese, before consigning them to a lifetime of perhaps unnecessary warfarin therapy. Certainly a stronger case can be made for taking a sleep history in all patients with atrial fibrillation.

      (1) Singer DE. A 60-year-old woman with atrial fibrillation. JAMA. 2003;290:2182-9.

      (2) Osler W. The Principles and Practice of Medicine. 6th ed., revised. New York: D. Appleton, 1907;835.

      (3) Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165:1217-39.

      (4) Shamsuzzaman AS, Gersh BJ, Somers VK. Obstructive sleep apnea: implications for cardiac and vascular disease. JAMA. 2003;290:1906-14.

      (5) Kanagala R, Murali NS, Friedman PA, Ammash NM, Gersh BJ, Ballman KV, Shamsuzzaman AS, Somers VK. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation. 2003;107:2589-94.


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    1. On 2016 Jul 23, Lydia Maniatis commented:

      Part three: Here's an instant update: It seems that, a few years after this publication, the "merged models" were tested. They failed. This is to be expected with ad hoc models, but at least it shows that the authors were sincere in their attempts, though this doesn't excue sloppy reasoning at that level. They also seem inclined to continue in the same style ("adding components" to the failed models rather than rethinking their ideas). The transparency-requiring low-level channel assumptions are apparently untouchable, non-negotiable. I know it's a cliche, but it's a recipe for misguided Ptolemaic solar system-level complexity, as the authors demonstrate.

      The article is "Probed-sinewave paradigm: a test of models of light-adaptation dynamics. Hood DC1, Graham N, von Wiegand TE, Chase VM" and its authors frankly acknowledge the utter failure of their hypothesis:

      "Our purpose here was to explore a relatively unused paradigm, the probed-sinewave paradigm, as a vehicle for distinguishing among candidate models of light adaptation. The paradigm produced orderly data with clear features. The candidate light-adaptation models, however, were unable to predict these features and our attempts to rescue them by changing parameter values and the decision rule were unsuccessful. While it is plausible that other modifications would produce predictions closer to the data, it is hard to believe these models can be rescued without adding additional components. For discussion, we divide these possible components into those that seem to require an additional channel vs those components that can be added to the single-channel of the models in Fig. 6."

      "While this discussion suggests a number of plausible directions for future work, it is not at all clear which direction or model will ultimately prove most successful. We started with a paradigm we thought would be a strong test of existing models; the test turned out to be even stronger than we expected."

      So pretty much starting at zero, after all that. Performing a strong test was the right move. The wrong move was not realizing, on the basis of solid reasoning, that the theoretical foundation of the model was flimsy and that models with such flimsy foundations are bound to fail unless you are extraordinarily lucky.

      Let me add that all models eventually fail, but it is the case of well-reasoned ones that these failures are informative, and necessary.


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    2. On 2016 Jul 23, Lydia Maniatis commented:

      Part two: Popper has discussed traditions such as those described and illustrated above, and concluded that they are not the kind of traditions that endow scientific activity with its progressive character. He suggested that we choose not to immunize our hypotheses with the tactics discussed above, e.g. leaving problems for the future and piling ad hoc model on top of ad hoc model, and having tolerance for logical inconsistencies. But that's a harder way than the vagueness, sloppiness and special pleading masked in technical complexity that has come to dominate contemporary vision science and in fact almost the whole of science today.


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    3. On 2016 Jul 23, Lydia Maniatis commented:

      This article is illustrative of the degradation of theory and practice in vision science. The article is not new (but compare with, e.g. Graham, 2011), but many of its assumptions and the style of argument - tolerance for layers upon layers of uncorroborated assumptions and inadequate, ad hoc models - are still very current and underpin a broad swath of contemporary (arguably pseudoscientific) activity. Below are quotes from the article and my comments.

      The abstract: "Light adaptation has been studied using both aperiodic and periodic stimuli. Two well-documented phenomena are described: the background-onset effect (from an aperiodic-stimulus tradition) and high-temporal-frequency linearity (from the periodic-stimulus tradition). These phenomena have been explained within two different theoretical frameworks. Here we briefly review those frameworks. We then show that the models developed to predict the phenomenon from one tradition cannot predict the phenomenon from the other tradition, but that the models from the two traditions can be merged into a class of models that predicts both phenomena."

      Comment: One wonders whether the merger was ultimately successful, and whether falsifying phenomena from yet other traditions could be merged with these two, to expand the ever-expanding ad hoc circle of tradition.

      Note that the piecemeal "merger" philosophy expressed by Graham and Hood seems to preclude falsification. Falsifying phenomena from another "tradition" simply lead to the summing of individual ad hoc models into a compound ad hoc model, and so on. The complexity but not the information content of the models will thus increase. (This will also likely produce internal inconsistencies that not be noticed because they will not be looked for.) The question of whether these models correspond with the facts that they are supposedly trying to explain never really arises.

      All this can be garnered from the abstract: If anything, the text is even worse.

      "None of the parts of the merged models, however, is necessarily correct in detail. Many modifications or substitutes would clearly work just as well at this qualitative level. …Also, one could certainly expand the model to include more parts. …Similarly, the initial gain-controlling process might be composed of several processes having somewhat different properties"

      Comment: The models are arbitrary, ad hoc, incomplete on their own terms, and there is no rational criterion for choosing among an infinite number of alternatives.

      "No attempt was made to fine-tune either model to predict all the details in any one set of psychophysical data…much less in all the other psychophysical results that such a model might bear on…To attempt such a project in the future might be worthwhile...particularly if the experimental results were all collected on the same subjects..."

      Comment: In other words, because the models are ad hoc they may only explain the results to which they were tailored. It may (or may not??) be worth checking to see whether this is the case. I.e. testing models for correspondence with the phenomena is optional. The effects in question are too fragile and too little understood to be tested across subjects with varying methods.

      "The more vaguely-stated possibility suggested by this observation, however, is that any decision rule of the kind considered here may be in principle inadequate for the suprathreshold-discrimination case. It may be impossible to explain suprathreshold discriminations without more explicit modeling of higher-level of higher-level visual processes than is necessary to explain detection (where detection is a discrimination between a stimulus and a neutral stimulus.)... Thus a simple decision rule may be suitable in the detection case simply because all the higher-level processes are reduced to such simple action THAT THEY BECOME TRANSPARENT." [caps mine].

      Comment: The idea that there are certain experimental conditions in which the conscious percept consists in the reading off of the activity of "low-level" neurons (as though there was a direct qualitative correspondence between neural firing and seeing, e.g., a blank screen!) is patently absurd and has been criticized in depth and from different angles by Teller (1984).

      Pretending that we take it seriously, we could refute it by noting that the presumably simplest of all stimuli - a white surface free of any imperfections - produces the perception of a three-dimensional fog. Other experiments have also shown that organizational processes are engaged even at threshold conditions, and that, indeed, they influence thresholds.

      The "transparency theory" is repeated by Graham (2011) in an article in Vision Research: "It is as if the near-threshold experiments made all higher levels of visual processing transparent, therefore allowing the properties of the low-level analyzers to be seen."

      This casually proposed "transparency" theory of near-threshold stimulation is apparently the basis of the widespread belief in spatial frequency channels and the extraordinary elaboration of associated assumptions. Without the transparency theory, it is not clear that even cherry-picked evidence can support this popular field of research. (If you've ever wondered at the widespread use of "Gabor patches" in vision research, this is the root cause - they are considered elemental due to the transparency theory-supported low-level neuron spatial frequency sensitivity hypothesis. I suspect many of the people using then don't even know why).

      Graham and Hood (1992) also go into a little finer detail about the putative basis of transparency: " In the suprathreshold discrimination case, the observer is trying to discriminate between two sets of neural responses…both of which sets contain many non-baseline responses. In the detection case…the observer is simply trying to detect some non-baseline responses in either set (since that is the set most likely to be the non-blank stimulus). Thus a simple decision rule may be suitable in the detection case simply because all the higher-level processes are reduced to such simple action that they become transparent."

      Comment: The suggestion that investigators are managing to set their low-level visual neurons at baseline at the start of experiments also seems implausible. I certainly don't think this has been explicitly discussed from the point of view of method. "However, at this moment in time, we seem to be able to explain background onset with a subtractive process…Thus, we can just leave as a marker for the future – should troubles in fully explaining the data arise – the possibility that the background-onset effect in particular (and perhaps all the results) will not be explained in detail without including more about higher-level visual processing."

      Comment: Translation: We'll accept our ad hoc hypo thesis for now, but it's probably wrong. But we'll worry about that later, if and when anyone makes trouble by bothering with actual tests. Because there's always a (zero) chance that it will be corroborated.

      Finally, the article also provides a good example of misleading use of references: "Quantal noise exists in the visual stimulus, as is well known (see Pelli for a current discussion.)"

      Comment: From Pelli, 1990: "It will be important to test the model…For gratings in dynamic white noise, this [model] prediction has been confirmed by Pelli (1981), disconfirmed by Kersten (1984) and reconfirmed by Thomas (1985). More work is needed." But we don't need to wait for evidence to firmly believe in "quantal noise."


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    1. On 2016 Mar 15, Kristina Hanspers commented:

      The gene regulation depicted in Fig 2 is available as a pathway in the Open Access Publication Collection at WikiPathways: http://wikipathways.org/index.php/Pathway:WP410. These pathways can be downloaded in several formats and can be used for analysis and visualization in tools like PathVisio and Cytoscape.


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    1. On 2016 Sep 09, Pavel Nesmiyanov commented:

      That is an interesting observation. Oligofructose-enriched inulin however even increased acetaldehyde production by microbiota.

      1. Joossens M, de Preter V, Ballet V, Verbeke K, Rutgeerts P, Vermeire S. Effect of oligofructose-enriched inulin (OF-IN) on bacterial composition and disease activity of patients with Crohn's disease: results from a double-blinded randomised controlled trial. Gut 2012; 61: 958.
      2. Joossens M, de Preter V, Ballet V, Verbeke K, Rutgeerts P, Vermeire S. Effect of oligofructose-enriched inulin (OF-IN) on bacterial composition and disease activity of patients with Crohn's disease: results from a double-blinded randomised controlled trial. Gut 2012; 61: 958.


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    1. On 2014 Nov 23, Harri Hemila commented:

      A manuscript version of the comment is available at the University of Helsinki institutional repository: http://hdl.handle.net/10250/7977 and the final version from DOI


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    1. On 2014 Jan 08, Brett Snodgrass commented:

      Dear Reader,

      This article provides an image of a well-preserved section of the the heart that exhibits a vessel of Wearn.

      For additional commentary on the normal anatomy (http://bit.ly/JTWearn) and the presentation in pathologic conditions, please see https://twitter.com/BrettSnodgrass1/status/392016004928131072

      I would like to thank Elsevier for making the article by Wearn open access.

      Comments and suggestions are welcome.

      Thank you kindly.


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    1. On 2014 Jan 08, Brett Snodgrass commented:

      Dear Reader,

      The myocardial sinusoids connect to the vasa Wearn, which connect to a coronary artery.

      Please see http://bit.ly/JTWearn

      For additional commentary, please see. https://twitter.com/BrettSnodgrass1/status/412195032486014976

      Please share if you agree or disagree with the previously proposed nomenclature and why.

      Thank you kindly.


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    1. On 2015 Feb 20, Jaime A. Teixeira da Silva commented:

      The authors developed some alternative methods for cryopreserving a single chrysanthemum cultivar ‘Escort’ while developing an ultra-rapid freezing protocol for nine chrysanthemum cultivars. In the controlled rate freezing protocol, the authors do not indicate how many shoot tips are placed into each cryovial nor for how long explants are maintained in LN. The same lack of detailed information exists for the encapsulation-dehydration (ED) protocol. In the vitrification protocol, the authors claim that shoot tips were added to a small drop of PVS2 on a sheet of aluminium that was then placed in cryovials and then plunged into LN. However, what was the function of adding the aluminium foil to cryovials? Only for the vitrification protocol do the authors state that “The vials were cooled from underneath to liquid nitrogen temperature to prevent boiling of the liquid nitrogen in the vials.” But it is not clear if such caution was exercised in the other cryopreservation protocols. The density or ratio of explants to medium is never indicated for any protocol. The commercial source of the cryovials and the reagents and equipment is also not described thus the experiment cannot be reliably reproduced. Throughout the manuscript, the authors use two terms, shoot tips and apical shoots to describe the exact same experimental explant, which could be confusing to amateur readers. Much of the description of the protocols is very repetitive and poorly written, and most of the “noise” in the protocol caused by this overlapping information could have been considerably reduced had the authors used suitable acronyms, e.g., SIM for shoot induction medium rather than defining all constituents every time. Fig. 1 legend contains a mistake: it should indicate –1°C but instead it is written as –0.1°C. In Fig. 2 legend, the claim that “There were no statistically significant differences between the different preculture procedures” might be incorrect, considering the wide span between 31% and ~45%. No statistical analyses were conducted on data in Table 1 and Fig. 3, so there is an inconsistent use of statistics and thus interpretation of the data set. All data is represented as only shoot % regeneration, which is not very informative. Shoot numbers would have also been useful. Even though the authors claimed to assess shoot % regeneration from shoot tips after 4 weeks or from callus after 8 weeks, none of the figures or tables indicate the source of the shoots (i.e., from callus or from shoot tips?). Each figure represents different sample sizes, with no apparent explanation, and there is absolutely no discussion about shoot regeneration from callus, which is an undesirable form of clonal propagation for chrysanthemum and could result in somaclonal variation.


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    1. On 2015 Dec 21, Stephen Strum commented:

      This is a critical paper that has been lost in the shuffle of time.


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    1. On 2013 Oct 30, Jamie Horder commented:

      This 1957 paper contains the observations of Leo Kanner and his colleague Leon Eisenberg, based on 120 autistic children seen at John Hopkins since Kanner defined the syndrome of "autism" in 1943.

      Notably, the authors in this paper suggested that the emotional 'coldness' often seen in parents of autistic children played some causal role in the development of the disorder - though only in conjunction with an 'inborn disturbance of affective contact', i.e. what would today be called a gene x environment interaction.

      This idea, taken further, later became notorious as the 'refrigerator mother' psychodynamic theory of autism, associated with the now-discredited Bruno Bettelheim.

      By 1971, Kanner denied advocating any kind of psychogenic hypothesis of autism: Kanner L, 1971. However such ideas are certainly evident in this paper.


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    1. On 2014 Jan 13, Brett Snodgrass commented:

      Dear Reader,

      Please provide your kind consideration to the following excerpt from page 502

      "There were thrombi in the Thebesian vessels (including the Thebesian veins, the myocardial sinusoids, arterio-luminal and arteriosinusoidal vessels)"

      The authors astutely document the various connections in the heart that were described by 1. Thebesius (Thebesian veins) http://bit.ly/vasaThebesii

      and the structures described by Joseph T. Wearn

       1. myocardial sinusoids   and the
      

      vessels of Wearn:

       2. arterio-luminal (arterioluminal) 
      
      
      3. arteriosinusoidal vessels
      

      http://bit.ly/JTWearn

      Referring to the vessels of Wearn as Thebesian vessels is problematic as the former are strictly arterial in nature. The vessels described by Thebesius were venular in nature.

      Reportedly, Thebesius only studied the veins. In addition, Thebesius neither defined nor studied the "myocardial sinusoids," "arterio-luminal (arteioluminal)," or "arteriosinusoidal" vessels.

      Those were defined utilizing serial histologic sections by Wearn et al. The myocardial sinusoids have not been included as strict components of the "vessels of Wearn" as they have been noted to connect with many structures, and Wearn reported that they have a "meandering course."

      Therefore, the arterial-cameral connections that bypass the capillary bed are probably best referred to as vessels of Wearn.

      The venular-cameral connections that bypass the capillary bed are probably best referred to as any of the synonyms, 1. Thebesian veins (personally preferred term) 2. vessels of Thebesius 3. vasa Thebesii

      At least one article uses the terms "Thebesian vessels" and "Thebesian veins" synonymously, (please ask for reference), and I agree that they are synonyms.

      However, using the term "Thebesian vessels" to apply to all of the aformentioned connections is both inaccurate and has probably resulted in much confusion in the literature. Therefore, the use of the term "Thebesian vessels," as used in this article, is probably not accurate.

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

      Comments and suggestions are welcome.

      Thank you very much.


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    1. On 2017 Apr 25, Guy Plunkett commented:

      When this paper was published journals did not host supplementary material on their own servers, and those links in the paper are no longer valid, having suffered the consequences of site death as individuals retired or moved on. In January 2014, Dr. Gerdes reached out to me, and since then we have been hosting a full copy of the Supplemental Data at https://www.genome.wisc.edu/Gerdes2003/


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    1. On 2017 Nov 10, Thomas Heston commented:

      This concept has stood the test of time. More and more research is showing beneficial effects of sauna bathing. An update of this topic is Sauna Bathing and the Cardiovascular System Int J Sci Res. 2017 Nov; 6(11) 569-570.


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    1. On 2014 Jan 08, Brett Snodgrass commented:

      Dear Authors,

      Thank you for the excellent article.

      Might the pathogenesis of this case be explained by a vessel of Wearn that disrupted vasculogenesis?

      The following linked image contains notes and references related to the probable pathogenesis in this case. https://twitter.com/BrettSnodgrass1/status/415991920104452096

      Comments, disagreements, and suggestions are welcome.

      Thank you kindly.


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    1. On 2015 Aug 27, Bernard Friedenson commented:

      For more information please see the article entitled "Mutations in Breast Cancer Exome Sequences Predict Susceptibility to Infection and Converge on the Same Signaling Pathways" This article is available at http://la-press.com/article.php?article_id=5029


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    1. On 2016 Jan 04, S A Ostroumov commented:

      Rotifers: Rotifers are an important part of the freshwater zooplankton, being a major foodsource and with many species also contributing to the decomposition of soil organic matter. Most rotifers are around 0.1–0.5 mm long, and are common in freshwater environments throughout the world. The word "rotifer" is derived from a Latin word meaning "wheel-bearer", due to the corona around the mouth that in concerted sequential motion resembles a wheel (though the organ does not actually rotate). The coronal cilia create a current that sweeps food into the mouth. Rotifers eat particulate organic detritus, dead bacteria, algae, and protozoans. They eat particles up to 10 micrometres in size. Like crustaceans, rotifers contribute to nutrient recycling. For this reason, they are used in fish tanks to help clean the water, to prevent clouds of waste matter.(Wikipedia was used).


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    2. On 2016 Jan 04, S A Ostroumov commented:

      ABSTRACT: This paper discovered new type of toxicity of the cationic surfactant tetradecyltrimethylammonium bromide (TDTMA); a new toxic effect of this chemical was discovered: inhibition of water filtration by rotifers. This chemical exemplifies a new type of hazardous contaminants (pollutants) of water.


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    3. On 2016 Jan 04, S A Ostroumov commented:

      EXPLANATION of and comment on TERMINOLOGY: cationic amphiphilic compound = cationic surfactant, Surface-Active Agent, in this paper it is the cationic surfactant tetradecyltrimethylammonium bromide (TDTMA); surfactants are a new class of water-polluting chemicals.


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    4. On 2015 Dec 06, S A Ostroumov commented:

      FULL TEXT ONLINE FREE, ALSO, THE ABSTRACT: https://www.researchgate.net/publication/200578650


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    1. On 2015 Dec 16, Farrel Buchinsky commented:

      This study reports that HPV 16 or 18 was detected in 24 out of 35 papilloma specimens. Absent carcinoma, no other study has reported such a high incidence of HPV 16 or 18 in benign recurrent respiratory papillomatosis. Therefore such a claim would require extraordinary evidence. It is possible that their primers had non-specific binding to DNA from other HPV types.


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    1. On 2013 Jun 20, Robert Tibshirani commented:

      This is an important paper, introducing the RMA method for normalizing Affymetrix probe-level data. RMA is now widely used in the R package and other software environments.


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    1. 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


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    1. On 2015 Dec 15, S A Ostroumov commented:

      Review (WorldCatalog) of the paper: Synecological Approach to the Problem of Eutrophication (new solution to the problem) https://www.researchgate.net/publication/286921503


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    2. On 2015 Dec 04, S A Ostroumov commented:

      FULL TEXT ONLINE FREE: The synecological approach to the problem of eutrophication. https://www.researchgate.net/publication/10614405;


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    3. On 2015 Nov 30, S A Ostroumov commented:

      Abstract of this paper, with some comment. ** The content of the article in short: A new solution to eutrophication. New concept of eutrophication control. Rating of this paper: In the top 25% of all articles scored by Altmetric. ** A new way of eutrophication control was suggested in the paper. The author suggested a new component of the measures against eutrophication: reducing the input of the chemical pollutants that weaken the potential of the filter-feeders for removing planktonic algae. The suggested way of controlling eutrophication is applicable to both freshwater and marine ecosystems. The article proposed a new idea, a new way of controlling eutrophication. The article is based on a series of the author's experiments with aquatic organisms (filter-feeders) that discovered and quantified relevant toxic effects of organic pollutants at sublethal concetrations. This article presented some new data to continue this line of research that is essential to the new solution to eutrophication. Among new facts that were reported in the paper, in addition to a substantial amount of relevant, related data previously obtained by the author: The liquid detergent (exemplified by the dish washing liquid, Fairy) 2 mg/L inhibited filtration by the bivalve mollusks, marine mussels (Mytilus galloprovincialis) within 2-23 min after addition, at temperature 22.5 ºС. This species of bivalve mollusks is one of key species in marine benthic ecosystems; it is one of ecological engineers that make a great impact on water quality. This is only one new fact that adds to many other facts (on how chemical pollutants can inhibit water filtration) discovered and reported by the author in other publications (papers and the book, Biological Effects of Surfactants). The paper presents a new approach to combat eutrophication.


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    1. On 2016 Jan 09, S A Ostroumov commented:

      DOI: 10.1023/A:1012348127085; 'two-level synergism' is a new scientific term suggested by the author, it is explained in the text of the article.


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    2. On 2015 Dec 04, S A Ostroumov commented:

      Abstract: The author identified a new type of ecological hazard of anthropogenic impact (using chemical pollution as an example), which he proposed to term “synecological summation” or “synergistic summation” of anthropogenic effects on organisms of two adjacent trophic levels. ** NEW FACTS: in the study reported in the paper, the following new type of environmental hazards was found. It was shown that even some relatively mild influences on organisms of two adjacent trophic levels may eventually produce a synergistic, pronounced and definitely undesirable effect which will lead to an abnormal increase in the abundance of organisms of one of the trophic levels. The concrete examples of that type of synergism were found when anthropogenic impacts affected the organisms of two adjacent trophic levels (bivalves and algae). Some new bioeffects of the action of the synthetic detergent (exemplified by the laundry detergent, namely, the detergent 'Vesna') (1 mg/l) on the bivalves, oysters Crassostrea gigas were described. Also, some new effects of the detergent (exemplified by the laundry detergent, namely, the detegent 'IXI') (10 mg/l) on the marine mussels Mytilus galloprovincialis, were found; also, new effects of the detergent (exemplified by the laundry detergent, namely the detergent 'Tide-Lemon') (50 mg/l) on M. galloprovincialis were discovered. ** CONCLUSION: The hazard of simultaneous influence of contamination of environment (e.g., by detergents) on organisms of the two trophic levels may occur when the polluting chemicals produce effects on algae and bivalves that are filter-feeders. It means that a new type of environmental hazards was discovered. [MAIK Nauka/Interperiodica, distributed by Springer Science+Business Media LLC.; ISSN 0012-4966 (Print) 1608-3105 (Online)]; DOI 10.1023/A:1012348127085;


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    3. On 2015 Dec 04, S A Ostroumov commented:

      FULL TEXT OF THIS ARTICLE ONLINE FREE: (TITLE: The hazard of a two-level synergism of synecological summation of anthropogenic effects); https://www.researchgate.net/publication/10614388


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    1. On 2016 Apr 15, S A Ostroumov commented:

      Unio is one of the most common freshwater bivalve mollusks. This species has a huge importance to water quality in rivers.


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    2. On 2016 Jan 09, S A Ostroumov commented:

      DOI 10.1023/A:1012344026176. Full text is available on ResearchGate.


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    3. On 2015 Dec 04, S A Ostroumov commented:

      Abstract: Responses of the freshwater bivalve Unio tumidus to mixed chemical preparations and the hazard of synecological summation of anthropogenic effects. - Doklady Biological Sciences, 2001, Volume 380, p. 492-495. ISSN 0012-4966 (Print) 1608-3105 (Online). DOI 10.1023/A:1012344026176. The author introduced a new concept and term, “the synecological summation of the effects of anthropogenic factors on organisms”. In the new author’s experiments, the effects of commercial detergents, which are chemical mixtures, on bivalves (e.g. effects of the laundry detergent OMO on the freshwater mussels Unio tumidus) were discovered and studied. Detergents exert two types of hazardous effects on organisms and ecosystems: the phosphorus-induced stimulation of phytoplankton growth and surfactant-induced inhibition of filter-feeders. Because filter-feeders are an effective natural factor of control of unicellular plankton populations, the two types of the detergent-induced effects on ecosystem facilitate the growth of phytoplankton populations. Therefore, these effects sum together, thereby increasing the hazard of the man-made impact on the ecosystem. The results contribute to a better understanding of the potential ecological danger of pollutants for integral functions of ecosystems. It is the synecological summation of the effects of anthropogenic factors on plankton populations and filter-feeders that is of particular concern. The interaction between populations of plankton organisms and filter-feeders that feed on plankton should be taken into consideration in the studies on the ecological effects of synthetic detergents on these populations. Situations of man-made impact should be analyzed with using the synecological approach to the problem. http://sites.google.com/site/2001dbs380p492unio/; www.springerlink.com/index/L33309208H28L87R.pdf; DOI 10.1023/A:1012344026176;


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    4. On 2015 Dec 04, S A Ostroumov commented:

      ANOTHER LINK, THE FULL TEXT OF THIS ARTICLE ONLINE FREE: https://www.researchgate.net/publication/10614386 ; [Dokl. Biol. Sci. 2001;380:492-495. Responses of Unio tumidus to mixed chemical preparations and the hazard of synecological summation of anthropogenic effects.]


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    5. On 2015 Dec 04, S A Ostroumov commented:

      This article ranked 1st among all papers in the journal, Doklady Biological Sciences; (Altmetrics) (on 26.01.2015). Article was published in a peer reviewed journal.


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    6. On 2015 Dec 04, S A Ostroumov commented:

      FULL TEXT OF THIS ARTICLE FREE, AVAILABLE ONLINE (Responses of Unio tumidus to mixed chemical preparations and the hazard of synecological summation of anthropogenic effects): https://www.researchgate.net/publication/259579828


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    1. On 2015 Dec 14, S A Ostroumov commented:

      WorldCat review of the article: Pellets of Some Mollusks in the Biogeochemical Flows of C, N, P, Si, and Al. https://www.researchgate.net/publication/286780426


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    2. On 2015 Dec 13, S A Ostroumov commented:

      Explanation of methodology (some details on the choice of the biological species and chemicals to study). Why the great pond snail and freshwater mussels were studied in this reseach project: they are among the most common benthic species of invertebrates in water habitats of Eurasia. Their biomass is one of the biggest, or just the biggest, among aquatic invertebrates in Eurasia and other parts of the world. Why the plant species, Nuphar lutea (Yellow Water-lily) , was used in this research project: it is one of the most common aquatic plant species in the freshwater habitats of Eurasia. Why the plant species, Taraxacum officinale, was used in this research project: it is a common laboratory practice to feed the great pond snail with leaves of this higher plant. Why the synthetic surfactants ТDТМА (tetradecyltrimethylammonium bromide) and SDS (sodium dodecyl sulfate) were used: they are representatives of the two major classes of synthetic surfactants, namely, cationic surfactants, and anionic surfactants. These two chemicals were studied in many other publications of Dr. Sergei Ostroumov, so that lots of data to compare toxic effects of these chemicals on organisms are available. A detailed explanation of methodology was also published in the book Biological Effects of Surfactants (Ostroumov, 2005, https://www.researchgate.net/publication/200637626)


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    3. On 2015 Dec 13, S A Ostroumov commented:

      Comment on the biological species that were studied in this paper: the great pond snail is a species of large air-breathing freshwater snail, an aquatic pulmonate gastropod mollusk in the family Lymnaeidae. Range Description: A widespread species distributed in Asia (central, north and south and southeast), north America, north Africa and New Zealand. The great pond snail has a shiny yellowish brown shell.

      Nuphar lutea (Yellow Water-lily) is an aquatic plant of the family Nymphaeaceae, native to temperate regions of Europe, northwest Africa, and western Asia.

      Unio is a genus of medium-sized freshwater mussels, aquatic bivalve mollusks in the family Unionidae, the river mussels. Unio is the type genus of the family Unionidae. About this family: The range of distribution for this family is world-wide. It is at its most diverse in North America, with about 297 recognised taxa, but China and Southeast Asia also support very diverse faunas. Freshwater mussels occupy a wide range of habitats, but most often occupy lotic waters, i.e. flowing water such as rivers, streams and creeks.


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    4. On 2015 Dec 13, S A Ostroumov commented:

      Explanation of terminology: pellets are the particles of the undigested organic matter (mainly biomass of undigested food) that the aquatic mollusks (snails and freshwater mussels) excrete so that these mollusks function as engines that drive the transfer of a significant amount of the organic matter through aqautic ecosystems.


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    5. On 2015 Dec 05, S A Ostroumov commented:

      ABSTRACT AND FULL TEXT ONLINE FREE: https://www.researchgate.net/publication/259579605


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    1. On 2016 Jan 09, S A Ostroumov commented:

      DOI: 10.1023/a:1011600213221. This paper proved that even chemical pollutants that are not toxic to phytoplankton can influence abundance of the phytoplankton. It is intereting that some chemical pollutants (which are not nutrients) can finally stimulate the abundance of phytoplankton. How? See the article.


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    2. On 2015 Dec 18, S A Ostroumov commented:

      DOI of this article. DOI: 10.1023/a:1011600213221;


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    3. On 2015 Dec 18, S A Ostroumov commented:

      today: increase in rating of the article: Imbalance of Factors Providing Control of Unicellular Plankton Populations Exposed to Anthropogenic Impact; In the top 25% of all research publications; http://5bio5.blogspot.com/2015/12/today-increase-in-rating-of-article.html


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    4. On 2015 Dec 05, S A Ostroumov commented:

      ABSTRACT AND FULL TEXT ONLINE FREE: Imbalance of Factors Providing Control of Unicellular Plankton Populations Exposed to Anthropogenic Impact. https://www.researchgate.net/publication/10614342


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    1. On 2016 Jan 12, S A Ostroumov commented:

      Tags: surfactants, chemical mixtures, detergents, water, filtering, activity, oysters, Crassostrea gigas, aquaculture,


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    2. On 2016 Jan 12, S A Ostroumov commented:

      DOI: 10.1023/A:1019270825775


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    3. On 2015 Dec 05, S A Ostroumov commented:

      Full text of this ARTICLE free, and ABSTRACT: https://www.researchgate.net/publication/10614314; Explanation of some technical terminology: amphiphilic chemicals = synthetic surfactants, detergents that are potential pollutants;


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    1. On 2016 Feb 01, Morten Oksvold commented:

      Please note that this article is 1 out of 15 publications for which an independent investigation initiated by the University of Copenhagen has found suspicion of scientific dishonesty. The conclusion from the report was published July 23, 2012:

      http://news.ku.dk/all_news/2012/2012.8/indications_of_fraud_in_penkowas_early_research/

      This articles should therefore not be cited.


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    1. 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


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    1. On 2015 Dec 02, S A Ostroumov commented:

      Availability online of this article: Ostroumov S. A. Anthropogenic effects on the biota: towards a new system of principles and criteria for analysis of ecological hazards. Rivista di Biologia / Biology Forum. 2003. 96: 159-170. [ISSN 0035-6050] The full text: https://www.researchgate.net/publication/200581960; and: https://www.researchgate.net/publication/10669691;

      https://www.researchgate.net/publication/10669691_Anthropogenic_effects_on_the_biota_towards_a_new_system_of_principles_and_criteria_for_analysis_of_ecological_hazards;


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    1. On 2013 Nov 18, Lior Pachter commented:

      This software and server is no longer being supported. I recommend using FSA instead http://orangutan.math.berkeley.edu/fsa/


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    1. On 2013 Nov 18, Lior Pachter commented:

      The SLAM software is no longer being supported or maintained.


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    1. On 2015 Jan 19, Paul Korir commented:

      This paper claims that in about half (49%) of transcription units with multiple splice forms it appeared that usage of an alternative TSS was accompanied by alternative splicing of the initial exon. The authors therefore conclude that this might imply that alternative TSS may induce alternative splicing. However, if a transcription unit has a 50-50 chance of exhibiting this behaviour that would be the last conclusion that one could make. There are no positive epistemic implications that can be derived from a 50-50 chance; in fact, this is state with the maximal entropy and by extension the most uncertainty.


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    1. On 2014 Nov 24, Ivan Oransky commented:

      The first author of this paper has agreed to retract it and five others following a finding of misconduct by the Office of Research Integrity: http://retractionwatch.com/2014/11/20/former-vanderbilt-scientist-faked-nearly-70-images-will-retract-6-papers-ori/


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    1. On 2015 Oct 28, Peter Gøtzsche commented:

      The authors write that "approximately 50-60% of patients are thought to improve clinically as a consequence of antidepressant treatment." This is not correct. About 50% of the patients get better on an antidepressant and 40% on placebo, ie. only a 10% difference, and according to the patients’ own judgments, the drugs don’t work (1,2). Furthermore, these trials were not effectively blinded, and if atropine is put in the placebo to blind the trials better, even the psychiatrists cannot find any effect (3).

      The authors write that, "Currently there is no evidence to suggest that ECT causes any kind of brain damage, although temporary cognitive impairment is frequently reported" and that "ECT seems to be a safe procedure". This is not the case. ECT is highly controversial (4), patients report permanent memory problems (5), and there seems to be a death rate of about 1 per 1000 (6).

      Only one RCT met the inclusion criteria and that trial was a post-hoc analysis of data in elderly people who participated in the Nottingham trial. It would be of interest to readers to know what the Nottingham trial showed.

      1 Laughren TP. Overview for December 13 Meeting of Psychopharmacologic Drugs Advisory Committee (PDAC). 2006 Nov 16. Available online at: www.fda.gov/ohrms/dockets/ac/06/briefi ng/2006-4272b1-01-FDA.pdf (accessed 22 October 2012).

      2 Gøtzsche PC. Deadly psychiatry and organised denial. Copenhagen: People’s Press; 2015.

      3 Moncrieff J, Wessely S, Hardy R. Active placebos versus antidepressants for depression. Cochrane Database Systematic Reviews 2004;1:CD003012.

      4 Carney S, Geddes J. Electroconvulsive therapy. BMJ 2003;326:1343-4.

      5 Rose D, Wykes T, Leese M, Bindman J, Fleischmann P. Patients perspectives on electroconvulsive therapy: systematic review. BMJ 2003;326:1363-5.

      6 Read J, Bentall R. The effectiveness of electroconvulsive therapy: a literature review. Epidemiol Psichiatr Soc 2010 Oct-Dec;19:333-47.


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    1. On 2016 Feb 01, Morten Oksvold commented:

      Please note that this article is 1 out of 15 publications for which an independent investigation initiated by the University of Copenhagen has found suspicion of scientific dishonesty. The conclusion from the report was published July 23, 2012:

      http://news.ku.dk/all_news/2012/2012.8/indications_of_fraud_in_penkowas_early_research/

      This articles should therefore not be cited.


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    1. On 2017 May 23, Morten Oksvold commented:

      This article was retracted April 27 2017 together with eight other articles from the same group due to data manipulations.

      Please note that the retraction notice is visible in the PDF document only.

      http://www.jbc.org/content/278/35/32618.full.pdf?sid=a8d5dc2c-dd64-4b19-bf5e-c46f7deb9f49

      "This article has been withdrawn by the authors. Lanes 1-4 and lanes 7-10 of the G-JNK immunoblot in Fig. 1B were duplicated. In Fig. 2A, the DP-JNK immunoblots on the left were inappropriately manipulated. In Fig. 2A, the G-JNK immunoblots in the middle row were duplicated. In Fig. 3B, lanes 2 and 7 of the phosphorylated MBP panel were duplicated. In Fig. 5A, lane 1 of the Ras-GTP panel was inappropriately manipulated. Lanes 7 and 11 were duplicated. Because the original data are no longer available, in the interest of maintaining accuracy in the published scientific literature, the authors wish to withdraw this article. However, the authors have full confidence in the findings and conclusions of this paper."


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    1. On 2016 Feb 01, Morten Oksvold commented:

      Please note that this article is 1 out of 15 publications for which an independent investigation initiated by the University of Copenhagen has found suspicion of scientific dishonesty. The conclusion from the report was published July 23, 2012:

      http://news.ku.dk/all_news/2012/2012.8/indications_of_fraud_in_penkowas_early_research/

      This articles should therefore not be cited.


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    1. On 2013 Jun 15, Wolfgang Huber commented:

      We performed a re-analysis of the same data using a variety of other, more standard classification procedures and could not reproduce the reported prediction accuracy. It is possible that the reported prediction accuracy was measured in a way that is sensitive to over-fitting, due to the high-dimensionality of the data and the choices that can be made for data "pre-processing". Our analysis was summarised in Ruschhaupt M, 2004 (pdf: http://www-huber.embl.de/pub/pdf/sagmb_2004.pdf).


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    1. On 2015 Nov 30, S A Ostroumov commented:

      The results of this study are really interesting and innovative. I had some experience of studying phytoremediation with this plant species, Myriophyllum aquaticum (parrot feather). It has a high potential for decontamination of aquatic environment. This paper provided new facts in support of good prospects of using this plant species. The test system with rotifers (Brachionus calyciflorus) feeding on an algal species (Nannochloropsis spp.) is also an interesting feachure of this paper. This test system was successfully used also in this paper: www.researchgate.net/publication/200578650;


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    1. On 2016 May 26, Jeff Kiefer commented:

      It looks like DAVID has been updated May 2016 https://david-d.ncifcrf.gov/content.jsp?file=release.html.


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    2. On 2016 Mar 17, Jonathan Wren commented:

      URL relocated to: https://david.ncifcrf.gov/


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    3. On 2015 May 07, Jeff Kiefer commented:

      DAVID is continuously being used as evidenced by its numerous citations in current biomedical literature http://bit.ly/1FS1JgT. However, the data resources used by DAVID appear to not have been updated since 2009 http://david.abcc.ncifcrf.gov/helps/update.html. The fact that DAVID has not been updated going on 5 years calls into question the current utility of using this tool.


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    1. On 2014 May 15, Andrea Messori commented:

      Half-life of Factor VIII in patients with haemophilia A: comparison between B-domain deleted recombinant Factor VIII and full-length recombinant Factor VIII.

      The study by Gruppo et al. [1] has described an analysis in which the half-life of Factor VIII was compared among plasma-derived concentrates , B-domain deleted recombinant products (BDD-rFVIII), and full-length recombinant products (FL-rFVIII). While the issue of the differences between plasma-derived concentrates and recombinant products has been debated in very numerous papers, the difference in the half-life between BDD-rFVIII and FL-rFVIII is a quite original finding, particularly because the authors conducted a pooled analysis based on a specific meta-analytical model (random-effect model). In their meta-analysis, however, Gruppo et al. [1] did not present any Forest plot; furthermore, some details were missing concerning the methods (e.g. the statistical software used for the analysis) and the results (e.g. the evaluation of heterogeneity). For this reason, we have re-analyzed the half-life data reported by Gruppo et al. [1] in their Table 3 and Figure 2 for BDD-rFVIII and FL-rFVIII. Our analysis was based on the Open Meta-analyst software (Open Meta-Analyst, version 4.16.12, Tufts University, url http://tuftscaes.org/open_meta/) and included the assessment of heterogeneity. The results of our re-analysis (study-specific and meta-analytic values of half-life with Forest plot and estimates of confidence intervals and heterogeneity) are available at the following Internet link: http://www.osservatorioinnovazione.net/papers/gruppo2003-reanalysis.pdf Our estimates of half-life for BDD-rFVIII and FL-rFVIII are nearly identical to those found by Gruppo et al.[1]. As expected, our results have also confirmed that the half-life of BDD-rFVIII is significantly shorter than that of FL-rFVIII

      References

      1. Gruppo RA, Brown D, Wilkes MM, Navickis RJ. Comparative effectiveness of full-length and B-domain deleted factor VIII for prophylaxis--a meta-analysis. Haemophilia. 2003 May;9(3):251-60.


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    1. On 2016 Feb 01, Morten Oksvold commented:

      Please note that this article is 1 out of 15 publications for which an independent investigation initiated by the University of Copenhagen has found suspicion of scientific dishonesty. The conclusion from the report was published July 23, 2012:

      http://news.ku.dk/all_news/2012/2012.8/indications_of_fraud_in_penkowas_early_research/

      This articles should therefore not be cited.


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    1. On 2017 Jun 06, Egon Willighagen commented:

      A third paper about the CDK was published today in the J. Cheminform.: https://doi.org/10.1186/s13321-017-0220-4


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    2. On 2015 May 20, Egon Willighagen commented:

      This paper was recently made gold Open Access (CC-BY): http://chem-bla-ics.blogspot.nl/2015/04/cc-by-with-acs-author-choice-cdk-and.html


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    1. On 2017 Aug 19, thomas samaras commented:

      Forsen studied 165,000 military recruits and found that blood pressure increased with height. In addition, he found that birth weight correlated with height and weight at 18 years of age.


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    1. On 2014 Jan 14, Alex Lancaster commented:

      The link in the PubMed Central article is outdated, the current URL of the project is: http://www.pypop.org/


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    1. On 2015 Jun 02, thomas samaras commented:

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

      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.


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    1. On 2016 Feb 01, Morten Oksvold commented:

      Please note that this article is based on earlier research data by J. Sudbø, which again originate from data which has been shown to be manipulated and partly fabricated. An independent investigation at Oslo University Hospital concluded that this article should be retracted:

      http://www.ous-research.no/general/?k=general%2Fnews_articles&aid=5473

      (in Norwegian, please use link at the end of the article to get the full report)

      This article should therefore not be cited.


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    1. On 2013 Nov 24, John Sotos commented:

      The Journal‘s editorial oversight of Mack’s analysis of smallpox (1) was so flawed that the article should have been presented as medical history, not as a contribution to biodefense policy.

      Mack describes “average” smallpox characteristics in naturally occurring outbreaks. This represents a best-case scenario. The next outbreak will not be natural, and it may not be average.

      The Soviets, for example, weaponized a highly virulent variola strain (2) and treated their variola “with plastics and resins to increase its potency and longevity in the air” (3). Responsible policy cannot, therefore, assume that attacks will use an average strain and natural delivery of variola.

      Mack’s suggestion that “the media should provide more information about the dangers of vaccination” is exactly opposite the true need. In the same issue, Blendon et al (4) report that 25% of Americans believe death is a “likely” outcome of smallpox vaccination. The Journal should have caught the contradiction, and should have used its bully pulpit with lay readers and journalists to provide reminders of the safety of vaccination in appropriate populations.

      (1) Mack T. A different view of smallpox and vaccination. N Engl J Med 2003;348:460-3.

      (2) Alibek K. Biohazard. New York: Dell Publishing, 1999. Page 112

      (3) Statement for the Record by Richard Preston Before The Senate Judiciary Subcommittee on Technology, Terrorism & Government Information and the Senate Select Committee on Intelligence. Chemical and Biological Weapons Threats to America: Are We Prepared? April 22, 1998. Available at: http://judiciary.senate.gov/oldsite/preston.htm

      (4) Blendon RJ, DesRoches CM, Benson JM, Herrmann MJ, Taylor-Clark K, Weldon KJ. The public and the smallpox threat. N Engl J Med 2003;348:426-32.


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    1. On 2013 Nov 24, John Sotos commented:

      Using a mortality-only model of smallpox vaccination policies, Bozzette et al (1) calculate that pre-emptively vaccinating the general population saves lives if the probability of a high-impact airport attack is greater than 0.01.

      However, vaccine-related mortality generally occurs almost immediately, while vaccine-related protection fully lasts, it is thought, 3 to 5 years (2)(3). Thus, pre-emptive vaccination saves lives if the probability of attack is greater than 0.01 over 3 to 5 years, i.e. if the annual probability is 0.002 to 0.003 or higher. The 482 deaths predicted to result from a policy of pre-emptively vaccinating the population approximately equal the deaths from lightning strikes in the United States during a 5-year period (4).

      Furthermore, although the attack scenarios used in the model were developed in consultation with experts, the evil ingenuity of some humans should not be underestimated. Attack plans targeting entire cities certainly exist (5). Prudent policy-making would, therefore, model an “Attack Scenario X” which is more lethal than the worst attack experts can publicly discuss.

      These considerations make a policy of pre-attack population vaccination more attractive.

      1. Bozzette SA, Boer R, Bhatnagar V, et al. A model for a smallpox-vaccination policy. New Engl J Med 2003;348:416-25.

      2. http://www.bt.cdc.gov/agent/smallpox/overview/faq.asp, viewed on 9 Feb 2003.

      3. Arita I. Duration of immunity after smallpox vaccination: a study on vaccination policy against smallpox bioterrorism in Japan. Jpn J Infect Dis 2002;55:112-6.

      4. Lightning-Associated Injuries and Deaths Among Military Personnel — United States, 1998-2001. MMWR 2002;51:859-862.

      5. Alibek K. Biohazard: The Chilling True Story of the Largest Covert Weapons Program in the World — Told from the Inside by the Man Who Ran It. New York: Delta, 2000; 21.


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    1. On 2014 Jul 24, DATTATRAY PAWAR commented:

      An incorrect link has been provided for the full text. Kindly correct it. Regards.


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    1. On 2013 Dec 30, Tom Kindlon commented:

      My response, published in BMJ USA, "The need for history (and epistemology) lessons"

      My response, "The need for history (and epistemology) lessons", can be read at: http://www.bmj.com/rapid-response/2011/10/29/need-history-and-epistemology-lessons

      A version of this was published in BMJ USA(1)

      References:

      [1]. Kindlon TP. The need for history (and epistemology) lessons. BMJ USA 01/2003; BMJ:E190-191. doi:10.1136/bmjusa.03020004


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    1. On 2013 Nov 10, GianCarlo Panzica commented:

      The conclusions of this study have been partially corrected by the results of a following study (Pierman S, 2008), where we demonstrated that the administration of estradiol and dihydrotestosterone to adult ArKO males restored AVP-immunoreactivity in the lateral septum of ArKO males to levels observed in intact wild type males. Therefore the decrease of AVP immunoreactivity described in the present study is due to a lack of activational effects of estradiol, rather than to an organizational effect.


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    1. On 2016 Jan 06, S A Ostroumov commented:

      In the top 25% of all research outputs scored by Altmetric. https://www.researchgate.net/publication/259402820; Article titled: Identification of a New Type of Ecological Hazard of Chemicals: Inhibition of Processes of Ecological Remediation. DOI 10.1023/A:1019929305267; www.ncbi.nlm.nih.gov/pubmed/12469618; http://www.altmetric.com/details/3052799


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    2. On 2015 Dec 03, S A Ostroumov commented:

      Full text of this article is available, online free: https://www.researchgate.net/publication/259402820


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    3. On 2015 Dec 03, S A Ostroumov commented:

      ABSTRACT: Identification of a New Type of Ecological Hazard of Chemicals: Inhibition of Processes of Ecological Remediation. - Doklady Biological Sciences, Vol. 385, 2002, pp. 377–379. Translated from Doklady Akademii Nauk, Vol. 385, No. 4, 2002, pp. 571–573. The author (Moscow University) discovered and quantitatively characterized a new type of ecological hazard of chemical pollution of water, which involves inhibition of important processes of ecological remediation of ecosystems (water filtration by aquatic bivalves). Experiments were performed using mollusks (oysters), Crassostrea gigas Thunberg, and a cell suspension in the seawater. The cell suspension was a model of suspended matter in aquatic ecosystem; this species of one-cell organisms was taken just for convenience, as a model of suspended particles. The laundry detergent Lanza-Automat inhibited water filtration by oysters (Crassostrea gigas). As a result, the removal of the suspended particles from water was inhibited. This demonstrated a new type of ecological hazard caused by water pollution with chemical pollutants at sublethal concentrations. This hazard is associated with the fact that chemical pollution of water causes inhibition of the physiological activity of filter-feeders, thereby inhibiting the important ecological processes of water filtration. These ecological processes contribute significantly to improving water quality, water purification and the related remediation of aquatic ecosystems (their ecological repair).


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    1. On 2014 Nov 24, Ivan Oransky commented:

      The first author of this paper has agreed to retract it and five others following a finding of misconduct by the Office of Research Integrity: http://retractionwatch.com/2014/11/20/former-vanderbilt-scientist-faked-nearly-70-images-will-retract-6-papers-ori/


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    1. On 2016 Feb 19, E M Martínez-Cáceres commented:

      In the light of the recent PubMed comment by Morten Oksvold, the referenced research study was performed entirely in our research centre by the research team led by Dr. Martínez-Cáceres at the time with Dr. Espejo as predoctoral researcher. Hence, the EAE in vivo experiments were performed in Barcelona with no involvement from Dr. Penkowa, who was engaged as an expert histopathologist. Dr. Penkowa received processed and encoded samples with which she performed some of the histopathological studies. The results were returned to us for overall analysis and submission for publication. It was agreed that Dr. Penkowa would be co-author of the published work.


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    2. On 2016 Feb 01, Morten Oksvold commented:

      Please note that this article is 1 out of 15 publications for which an independent investigation initiated by the University of Copenhagen has found suspicion of scientific dishonesty. The conclusion from the report was published July 23, 2012:

      http://news.ku.dk/all_news/2012/2012.8/indications_of_fraud_in_penkowas_early_research/

      This articles should therefore not be cited.


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    1. On 2014 Oct 30, induprabha yadev commented:

      the only one prospective study included in the recent systematic review by Goh et all


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    1. On 2013 Oct 21, Gary Ward commented:

      This is a seminal paper in the field, for two reasons:

      1) It reported the development of a new, Tet-transactivator-based system for controlling gene expression in T. gondii. This system has since been widely adopted as a way to make conditional knockout parasites and is particularly useful for studying the function of essential genes in this haploid organism. For a powerful extension of this system based on promoter replacement, see Sheiner et al PLOS Pathogens 7 (2011) e1002392.

      2) In the first application of the new system, the authors demonstrated directly the importance of the parasite’s Class XIV myosin, TgMyoA, for gliding motility, host cell invasion and host cell egress. This observation led to a great deal of subsequent work on the myosin motor complex and its role in the biology of T. gondii and other apicomplexan parasites.

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


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    1. On 2014 Aug 01, Amanda Capes-Davis commented:

      Please be aware that this article has been retracted. Cell line TEC61 is not a thyroid cell line; it is actually JEG3, which is a choriocarcinoma cell line. Many thanks to the authors for providing this information.


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    1. 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


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    1. On 2016 Nov 07, David Juurlink commented:

      The primary outcome reported in this study differs considerably from the originally intended outcome. Readers are directed to our Cochrane Review Buckley NA, 2011 and an earlier related review Buckley NA, 2005 for details.


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    1. On 2017 May 10, Misha Koksharov commented:

      Could a Neuroscientist Understand a Microprocessor? http://biorxiv.org/content/early/2016/05/26/055624 - Jonas E, 2017 (This one also has several other interesting references, e.g. Marom S, 2009, Brown JW, 2014)

      And another one to the collection: "Can a Systems Biologist Fix a Tamagotchi?"


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    2. On 2017 May 09, Sophien Kamoun commented:

      Can a biologist fix a smartphone? https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-017-0378-2


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    1. On 2015 Mar 03, Ivan Oransky commented:

      The journal has issued an Expression of Concern: http://retractionwatch.com/2015/03/03/heart-journal-issues-expression-of-concern-after-fraud-report/


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    2. On 2014 Nov 24, Ivan Oransky commented:

      The fourth author of this paper has agreed to retract it and five others following a finding of misconduct by the Office of Research Integrity: http://retractionwatch.com/2014/11/20/former-vanderbilt-scientist-faked-nearly-70-images-will-retract-6-papers-ori/


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    1. 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.


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    2. On 2015 Jun 02, thomas samaras commented:

      None


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    1. On 2014 Feb 12, Diana Frame commented:

      A note for researchers, MESH indexing terms on this article erroneously tag it as non-small cell lung cancer (NSCLC). It should be under Small Cell Lung Carcinoma[MeSH].


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    1. On 2017 Sep 09, Michael Allen commented:

      The equations for disease impact number (DIN) and population impact number (PIN) are confusing according to the following examples in which the proportion with the diseased exposed to the treatment and the proportion of the population with the disease are both 0.1

      In example 1 NNT=100; DIN=1000; PIN=10000 In example 2 NNT=10; DIN=100; PIN=1000

      In these examples the only difference is the NNT (100 in example 1; 10 in example 2). A smaller NNT indicates a larger effect.

      However changing the NNT from 100 to 10 leads to a smaller DIN and PIN indicating a smaller effect.

      I have checked the way I calculated DIN and PIN against the authors' examples and they are correct.

      It seems the authors' equations for the DIN and PIN may be incorrect. Or am I missing something?


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    1. 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


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    1. On 2013 Oct 21, Hilda Bastian commented:

      The two ongoing studies discussed in this review have since been published. They are Ishikawa H, 2005 and Burn J, 2011, as discussed in this blog post.


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    1. On 2013 Oct 21, Hilda Bastian commented:

      The predominant weight for safety concerns about single-session debriefing in this systematic review are carried by a single trial, at high risk of bias. See discussion in my comment here: Bisson JI, 1997. The method of imputation of adverse events in this trial does not appear to be described in this review.

      A critical quality assessment of that trial was in part made by a systematic review author who was also an author of the trial. A more recent systematic review conducted by others (Gartlehner G, 2013), found the evidence on this intervention to be generally weak. There is further discussion in this blog post.


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    1. On 2016 Jan 06, S A Ostroumov commented:

      In the top 25% of all research outputs scored by Altmetric. https://www.researchgate.net/publication/259579921 DOI: 10.1023/A:1015398125876; PMID: 12053567 [PubMed - indexed for MEDLINE]; www.ncbi.nlm.nih.gov/pubmed/12053567;

      http://www.altmetric.com/details/3046537


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    2. On 2015 Dec 03, S A Ostroumov commented:

      ABSTRACT: System of principles for conservation of the biogeocenotic function and the biodiversity of filter-feeders.- Doklady Biological Sciences. 2002. Vol. 383: 147-150. Bibliogr. 15 refs. ISSN 0012-4966 (Print) 1608-3105 (Online). Distributed by Springer, orderdept@springer-sbm.com. ** Text of the ABSTRACT: As a result of the author’s studies of filter-feeders (previous publications in Russian: Doklady akademii nauk [DAN], 1998, Vol. 362, P. 574-576; Doklady akademii nauk [DAN], 2001, Vol. 378, P. 283-285), it is clear that the filtering activity of populations of filter-feeders in natural habitats might be significantly reduced if the concentrations of some pollutants reach certain levels. The role of filter-feeders as factors of water purification in ecosystems is so important that their inhibition is a danger for the entire ecosystem. The author emphasizes that not only the biodiversity of filter-feeders but also their level of functional (filtration) activity is to be protected. In order to do so, the author suggested establishing a new type of protected areas whose main purpose is to protect functionally active populations of filter-feeders, including bivalves and other organisms. Those protected areas could be named hydrobiological (some variants: biofiltering, or malacological) reserves (some variants: refuges, sanctuaries, etc.). The author formulated 5 principles of nature conservation requirements in malacological and hydrobiological reserves (Tabl. 3). Among them is principle 2, "conservation of filtration activity of organisms and populations". The paper contains data on how 5 detergents (1-50 mg/L) inhibited the filtration activity of Unio tumidus, Mytilus galloprovincialis, Crassostrea gigas (Tabl. 2); on effects on the efficiency of elimination (EEE) of suspended matter from water were measured (Tabl. 2); on the number of days (0.3 – 10) needed to filter the volume of aquatic (freshwater and marine) ecosystem by the local bivalves (a review of data from literature) (Tabl. 1). "I suggest that the existing system of protected terrestrial and water areas should be supplemented with special sites intended to conserve populations of filter-feeders. In addition to biodiversity conservation, these populations should be conserved because they fulfill a very important biogeocenotic function of water filtration and purification" (p.149). "The system of five principles…is proposed to provide an ecological basis of the environment conservation conditions at these sites (malacological and hydrobiological reserves)" (p.149).]. DOI 10.1023/A:1015398125876; www.springerlink.com/index/1MNVLNAYW36TC92R.pdf


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    3. On 2015 Dec 03, S A Ostroumov commented:

      Full text, free, available online: https://www.researchgate.net/publication/259579921


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    1. On 2016 Jan 12, S A Ostroumov commented:

      This article has also its Russian version, published in the journal of Russian Academy of Sciences. The Russian version of this article is cited here: Rozenberg G.S. Idealizing object and fundamental notions of the modern ecology (with examples from vegetation ecology). ПОВОЛЖСКИЙ ЭКОЛОГИЧЕСКИЙ ЖУРНАЛ. 2002. № 3. С. 246 – 256.


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    2. On 2016 Jan 12, S A Ostroumov commented:

      DOI: 10.1023/a:1015393924967


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    3. On 2016 Jan 12, S A Ostroumov commented:

      In the top 25% of all research outputs scored by Altmetric


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    4. On 2016 Jan 12, S A Ostroumov commented:

      At World Catalog, the paper was reviewed and rated as excellent.


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    5. On 2015 Dec 14, S A Ostroumov commented:

      Full text of a review (with favorable evaluation) of this paper: https://www.researchgate.net/publication/286865472


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    6. On 2015 Dec 12, S A Ostroumov commented:

      Review (favorable) of this article was published. See: https://www.researchgate.net/publication/286625953


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    7. On 2015 Dec 03, S A Ostroumov commented:

      Full text of this article, free, is available online: https://www.researchgate.net/publication/200577836


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    8. On 2015 Dec 03, S A Ostroumov commented:

      ABSTRACT: Ostroumov S.A. New definitions of the concepts and terms ecosystem and biogeocenosis. - Doklady Biological Sciences, 2002, Volume 383, p. 141-143. [MAIK Nauka/Interperiodica distributed by Springer Science+Business Media LLC. ISSN 0012-4966 (Print) 1608-3105 (Online)]. In 1935, the term 'ecosystem' was coined by Prof.A. Tansley. In the 1940s, another important term 'biogeocoenosis' was introduced by Prof. V. N. Sukachev. Since that time, a significant amount of new facts was accumulated in ecology. It is necessary to revisit the formulation of the basic concepts and terms in ecology, including the two terms mentioned above. The author proposed some new variants of the definition of the two terms that (1) reflect the modern understanding of the basics of ecology; and (2) avoid the vicious circle of using other terms that in turn request their definitions. The author realizes that the new variants of the terms cannot be ideal and some other variants of the definitions are also possible. 5 specific features of the proposed definition of ecosystem (Table 1). 8 specific features of the proposed definition of biogeocenosis, and 8 distinctions between the proposed definition and the classical definition by V.N.Sukachev (Table 2)].


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    1. On 2015 Dec 03, S A Ostroumov commented:

      ABSTRACT of this article: A new type of effect of potentially hazardous substances: uncouplers of pelagial–benthal coupling. - Doklady Biological Sciences. 2002. Vol. 383 (1-6): 127-130. Bibliogr.15. ISSN 0012-4966. Discovery of a new type of negative impact of pollutants on the biosphere, as a result of inhibition of water filtration by filter-feeders / suspension feeders. The water filtration and associated removal of suspended matter from water is part of migration of matter. As V.I. Vernadsky stressed, organisms are mediators or driving force of “biogenic migration of atoms in the biosphere”. This migration is partly implemented in the framework of pelagial–benthal coupling via the activity of filter-feeders, which remove the organic suspended matter from water and excrete pellets. The tables contains the following data: the average percentage of assimilated (16-90%) and non-assimilated (10-84%) food matter for 15 large taxa of invertebrates (Table 1); potassium bichromate inhibited water filtration by mussels Mytilus galloprovincialis (Table 2); surfactants, detergents, pesticides inhibited filtration by filter-feeders, marine and freshwater bivalves and rotifers (Table 3). A prediction is made: "Further research and experimental studies are expected to provide new evidence that sublethal concentrations of chemical pollutants induce a significant decrease in the filtration capacity of freshwater and marine filter feeders" (p.129). "The uncoupling process considered above is an anthropogenic violation of two basic laws (empirical rules or biogeochemical principles) of the biosphere functioning: (1) biogenic migration of atoms of chemical elements in the biosphere always tends toward its maximum expression; (2) on the geological time scale, the evolution of species gives rise to the forms of life that are stable in the biosphere, and is so directed that the biogenic migration of atoms in the biosphere increases" (p.129).]; DOI 10.1023/A:1015385723150;


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    2. On 2015 Dec 03, S A Ostroumov commented:

      Full text of this paper is available online free: A new type of effect of potentially hazardous substances: uncouplers of pelagial–benthal coupling. https://www.researchgate.net/publication/200576296


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    1. On 2015 Sep 04, Lydia Maniatis commented:

      Lower region was not a new cue in 2002. Rubin discussed it in his article "Visual wahrgenommene Figuren" (1921). I haven't read it, but Kohler mentions it in a book called "Dynamics in Psychology" ((1940): "Rubin found that in such cases certain rules decide which part will preferably acquire the figure-character. One of these rules says that, if two adjacent areas appear one above the other, and if no other principle interferes, the lower part rather than the upper will be seen as shaped and as substantial" (p. 23).

      It might be worth translating Rubin's original work into English.


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    1. On 2017 Jul 07, Morten Oksvold commented:

      This article should have been retracted after an investigation by The University of Maryland found this article to contain "compromised" data (a total of 26 articles in 11 journals were affected). The journal Cancer Research was informed in August 2016, according to Retraction Watch.

      http://retractionwatch.com/2017/04/26/university-asked-numerous-retractions-eight-months-later-three-journals-done-nothing/


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    1. On 2017 Sep 10, Erik Gotfredsen commented:

      The name "Turpinia ternata" is misspelled in the abstract


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    1. 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.


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    1. On 2016 Jan 06, S A Ostroumov commented:

      In the top 25% of all research outputs scored by Altmetric. https://www.researchgate.net/publication/11371556; DOI 10.1023/A:1014465220673.

      http://www.altmetric.com/details/3041761;


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    2. On 2015 Dec 03, S A Ostroumov commented:

      Full text, free, is available online, of this article: Biodiversity protection and water quality: the role of feedbacks in ecosystems. https://www.researchgate.net/publication/259497389;


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    3. On 2015 Dec 03, S A Ostroumov commented:

      ABSTRACT: The article presents a new fundamental concept of how biodiversity helps towards a better environmental stability and water quality. The author made an innovative analysis of his experimental data and formulated the following fundamental principle: to maintain water quality, it is vital to protect the functionally active biodiversity of water ecosystems. In other words, according to the author’s new concept, the protection of functionally active biodiversity, including filter-feeders, is a key to maintenance of water quality. This concept was supported by many facts obtained in experiments of the author and reported in his previous publications. This article presents new facts in support of his concepts. Among new facts obtained and reported in the paper: a chemical pollutant (exemplified by the laundry detergent IXI, at a sublethal concentration 20 mg/L) inhibited water filtration by the aquatic bivalve mollusks, marine mussels Mytilus galloprovincialis (3-25 min, 18 pro mille, 22.8ºC). Another synthetic detergent (exemplified by the laundry detergent Deni-Automat), at a sublethal concentration 30 mg/L, also inhibited the water filtration by the marine bivalves oysters Crassostrea gigas (2-40 min, 25.2ºC).]. These new data as well as the other related data obtained by the same author and reported in his other publications, supported the author’s fundamental concept.


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    1. On 2017 Jan 20, Eric Yarnell commented:

      The authors family and given names have been thoroughly mixed up. The author citation should be (from the original article directly): Ho YK, Kim SH, Lee WJ, Byrne HK


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    1. On 2016 Jan 09, Chao Liu commented:

      There are also a good body of evidence, both from animal and human, shows that glucocorticoids could promote renal water and sodium excretion. Thus, patients with decompensated heart failure may benefit from glucocorticoids.

      1. Hunter RW, Ivy JR, Bailey MA. Glucocorticoids and renal Na+ transport: implications for hypertension and salt sensitivity. J Physiol. 2014 Apr 15;592(Pt8):1731-44.

      2. Landínez RAS, Romero MFL, Maurice EH (2014). Efectos de la prednisona sobre la función renal a corto plazo en pacientes con Insuficiencia Cardíaca Descompensada. Venezolana de Medicina Interna 30(3): 176-192.

      3. Liu C, Chen Y, Kang Y, Ni Z, Xiu H, Guan J, et al. (2011). Glucocorticoids Improve Renal Responsiveness to Atrial Natriuretic Peptide by Up-Regulating Natriuretic Peptide Receptor-A Expression in the Renal Inner Medullary Collecting Duct in Decompensated Heart Failure. J Pharmacol Exp Ther 339(1): 203-209.

      4. Liu C, Liu G, Zhou C, Ji Z, Zhen Y, Liu K (2007). Potent diuretic effects of prednisone in heart failure patients with refractory diuretic resistance. Can J Cardiol 23(11): 865-868.

      5. Liu C, Liu K (2014a). Effects of glucocorticoids in potentiating diuresis in heart failure patients with diuretic resistance. Journal of cardiac failure 20(9): 625-629.

      6. Liu C, Liu K (2014b). Reply to Day et al.--hypouricemic effect of prednisone in heart failure: possible mechanisms. Can J Cardiol 30(3): 376 e373.

      7. Liu C, Zhao Q, Zhen Y, Gao Y, Tian L, Wang L, et al. (2013). Prednisone in Uric Acid lowering in Symptomatic Heart Failure Patients With Hyperuricemia (PUSH-PATH) study. Can J Cardiol 29(9): 1048-1054.

      8. Liu C, Zhao Q, Zhen Y, Zhai J, Liu G, Zheng M, et al. (2015). Effect of Corticosteroid on Renal Water and Sodium Excretion in Symptomatic Heart Failure: Prednisone for Renal Function Improvement Evaluation Study. J Cardiovasc Pharmacol 66(3): 316-322.

      9. Meng H, Liu G, Zhai J, Zhen Y, Zhao Q, Zheng M, et al. (2015). Prednisone in Uric Acid Lowering in Symptomatic Heart Failure Patients with Hyperuricemia - The PUSH-PATH3 Study. The Journal of rheumatology 42(5): 866-869.


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    1. On 2016 Mar 12, Mark Milton commented:

      This article contains the following statement "Recombinant proteins with a molecular weight of greater than 60 kd may be taken up by the reticuloendothelial system and catabolized by the liver." No reference was provided to substantiate this statement and is in conflict with "conventional wisdom" regarding the clearance of proteins, including therapeutic IgG antibodies. I would encourage readers not to cite this article when describing how therapeutic proteins and antibodies are cleared from the body.


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    1. 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


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    1. On 2016 Feb 01, Morten Oksvold commented:

      Please note that this article is 1 out of 15 publications for which an independent investigation initiated by the University of Copenhagen has found suspicion of scientific dishonesty. The conclusion from the report was published July 23, 2012:

      http://news.ku.dk/all_news/2012/2012.8/indications_of_fraud_in_penkowas_early_research/

      This articles should therefore not be cited.


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    1. On 2015 Oct 15, Lydia Maniatis commented:

      There was absolutely no reason for this study, which tests two highly-flammable straw men. That it was deemed worth doing indicates either ignorance of fundamental principles of perception or an inexplicable failure to take them into account.

      What is supposedly being tested is the impossible notion that we are able to estimate the physical illumination of a scene directly. Nobody believes this, because a. it is logically impossible and b. there are mountains of evidence against it. The authors don't suggest that any believes it, saying only that a “natural expression of the illumination-estimation hypothesis is that perceived illumination is determined by [actual illumination].” But there is nothing natural about such a claim, logically or empirically. First, there is no conceivable mechanism by which direction and intensity of (often partially-obstructed and/or multiple) light sources (which, furthermore, we never look at directly) falling on each local surface could be estimated. (This applies to the conditions of this experiment as well). Second, if illumination could be directly evaluated, then interpretation of the lightness of surfaces would not require a global, ratio-based approach, but could be estimated based on local luminance info only, by factoring out the independently-estimated illumination. If illumination could be directly evaluated, then a photograph of sunlight and shadow would completely lack this character if placed under a visible light-bulb evenly-illuminating the entire surface. In general, graphic representations of shadows, transparencies, etc. would be impossible. It is a fundamental fact of visual perception that the visual system uses the light reflected from a scene, not the light impinging on it, to estimate reflectance, illumination and everything else. The authors are, naturally aware of this, as reflected in their casual acknowledgment that “good constancy” under changing illumination “depends critically on the scene manipulations (Kraft and Brainard, 1999)” and when they say that the “poor constancy” they found in this experiment might be to the lack of a “number of [stimulus] cues often taken to support constancy.” Direct estimation of the illuminant would not need the support of such “cues” coming from the stimulus itself. No surprise, then, that the proposed “hypothesis” is falsified. Furthermore, the authors are unable to suggest any plausible interpretation of their results.

      A second pseudo-hypothesis tested is that simultaneous contrast is a consequence of perceived illumination differences, even though we know that it arises when illumination appears homogeneous. This was also falsified.

      A strange suggestion made (and rejected) in the conclusion of the paper is that “one could attempt to understand our results while preserving the elegance of the [our version of the] illumination estimation hypothesis by replacing the physical luminance ...with a perceived quantity.” I'm not sure what this means, but luminance is not perceived. If it is, then what does it look like? On what info would this evaluation be based?


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    1. On 2013 Nov 25, Colleen Doherty commented:

      One interesting thing I discovered after this publication. To achieve the observed difference in CBF2 induction levels between wild type and camta3 mutant plants, these experiments had to be performed at the same time of day relative to imbibition, even in constant light. This time seems to correspond with dawn as it is the highest point of CBF2 induction in wild type plants.

      Some critical citations were missing from this article:

      The following papers were critical in our focus on this family of transcription factors. They were essential for our investigation into the CAMTA family. I believe the citations were omitted when we were rewriting the intro and the sentences referencing these early works were cut or reworded.

      YANG, T. and POOVAIAH, B.W. 2002. A Calmodulin-binding CGCG box DNA-binding protein family involved in multiple signaling pathways in plants. J. Biol. Chem. 277: 45049-45058.

      YANG, T. and POOVAIAH, B.W. 2000. An early ethylene up-regulated gene encoding a calmodulin-binding protein involved in plant senescence and death. J. Biol. Chem. 275: 38467-38473

      The position of the T-DNA insertions were overlaid on a figure taken from this paper. Although we do cite this paper elsewhere in the article, this is not properly cited as the source in the supplemental figure.

      Bouché, N., Scharlat, A., Snedden, W., Bouchez, D., and Fromm, H. (2002). A novel family of calmodulin-binding transcription activators in multicellular organisms. J. Biol. Chem. 277 21851–21861.


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    1. 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


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    1. On 2013 Oct 23, ANDREW SU commented:

      !MOVED http://biogps.org

      The URL in the original abstract has now been retired. This data set (together with other gene expression data sets) are now hosted at http://biogps.org.


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    1. On 2013 Dec 11, Gary Ward commented:

      This paper is a classic in the field of parasite cell biology. The stunning electron micrographs provide the first high-resolution look at the substructure of the conoid, a unique cytoskeletal structure found in a variety of apicomplexan parasites. The paper shows that the fibers of the conoid are composed of tubulin, but the protofilament arrangement within the individual fibers is unlike that of any other known tubulin-based structure: rather than a closed tube, the 9 protofilaments are arranged into a “comma” shape. This unique structure may enable the high degree of curvature required of these filaments within the thimble-shaped conoid (diameter 380 nm). FRAP experiments revealed the tubulin subunits are incorporated into the conoid during the early stages of daughter formation, but not in mature parasites. Remarkably, the authors also show that the pitch of the filaments changes as the conoid extends and retracts during parasite motility and host cell invasion.

      In the years since this paper was published, additional isoforms of α- and β-tubulin have been discovered for a total of three each (Hu et al. PLOS Pathog [2006] 2(2): e13). It would be interesting to see whether any of these isoforms localize specifically to the conoid or to the other tubulin-based structures within the parasite.

      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


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    1. On 2016 Sep 13, Gerhard Nebe-von-Caron commented:

      the paper states I claimed problems with the sorting of gram positive bacteria which is factually incorrect as I never made such statement, and definitively not in the cited paper.


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    1. 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.


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    1. On 2016 Feb 03, Daniel Schwartz commented:

      The SLEDAI-2K can easily be calculated using an online tool or mobile app: http://qxmd.com/calculate/sledai-2k

      Conflict of interest: Medical Director, QxMD


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    1. On 2015 Jun 02, thomas samaras commented:

      Additional information on height, CHD, longevity the environment 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.


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    1. On 2013 Oct 24, Tom Kindlon commented:

      (contd.)

      5 Van Houdenhove B, Onghena P, Neerinckx E, Hellin J: Does high "action-proneness" make people more vulnerable to chronic fatigue syndrome? A controlled psychometric study. J Psychosom Res 1995, 39:633-40.

      6 MacDonald KL, Osterholm MT, LeDell KH, White KE, Schenck CH, Chao CC, Persing DH, Johnson RC, Barker JM, Peterson PK: A case-control study to assess possible triggers and cofactors in chronic fatigue syndrome. Am J Med 1996, 100:548-54.

      7 Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006 Sep 16;333(7568):575. Epub 2006 Sep 1.

      8 White PD. "Overview of post-viral fatigue: CFS or what?". International Symposium on Viruses in CFS & Post-viral Fatigue - A satellite meeting of the 6th International Conference on HHV-6 & 7 in Baltimore (2008). http://scivee.tv/node/6895


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    2. On 2013 Oct 24, Tom Kindlon commented:

      This study did not have information on the physical fitness of the patients before becoming ill. The authors suggest that the patients may have been more inactive before becoming ill. However the evidence is stacking up that this is not generally the case and indeed that patients who develop CFS may, on average, be a little more active or fitter than the general population.

      A recent prospective population study<sup>1</sup> on the illness 4779 people from birth for the first 53 years of their lives. At age 53, 34 reported a diagnosis of CFS. Amongst other things, it found that "increased levels of exercise throughout childhood and early adult life and a lower body mass index were associated with an increased risk of later CFS." As it was a prospective study, there was no issue of recall bias. It also wasn't simply self-rated, as it also involved reporting by a teacher at age 13. Also they used the subject's BMI index - patients who went on to have CFS at age 53 had a (statistically significant) lower BMI than those who did not go on to develop CFS at ages 36 and 43 (before they had CFS). The authors say this "this may provide some indirect but objective evidence of increased levels of activity at these ages, especially as this difference had resolved by the age of 53 years" (when the people with CFS were no longer more active).

      A study involving the corresponding author<sup>2</sup> found that, compared to healthy controls, patients with chronic, unexplained fatigue rated themselves as more active before their illness. In this study, they also reported that "the high levels of physical activity reported by patients have been corroborated by their spouses, partners, or parents" (in another study<sup>3</sup> ). At least three other retrospective studies reporting that CFS patients perceived themselves as more active before their illness began than healthy controls.<sup>4-6</sup>

      In 2006, a CDC-funded prospective cohort study following patients from the time of acute infection with Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever), or Ross River virus (epidemic polyarthritis) was published.<sup>7</sup> 253 patients were enrolled and followed at regular intervals over 12 months by self report, structured interview, and clinical assessment. It found that prolonged illness was "characterised by disabling fatigue, musculoskeletal pain, neurocognitive difficulties, and mood disturbance was evident in 29 (12%) of 253 participants at six months, of whom 28 (11%) met the diagnostic criteria for chronic fatigue syndrome. This post-infective fatigue syndrome phenotype was stereotyped and occurred at a similar incidence after each infection. The syndrome was predicted largely by the severity of the acute illness".

      Given only a correlation was found and that no intervention was tested in the current study, along with the preceeding information, I believe the authors' suggestion that "prevention of postinfectious fatigue by an early return to physical activity may be possible" is highly speculative (this claim was recently re-iterated by the corresponding author at a conference on CFS when presenting data from this study<sup>8</sup> ).

      1 Harvey SB, Wadsworth M, Wessely S, Hotopf M: Etiology of Chronic Fatigue Syndrome: Testing Popular Hypotheses Using a National Birth Cohort Study. Psychosom Med. 2008 Mar 31

      2 Smith WR, White PD, Buchwald D. A case control study of premorbid and currently reported physical activity levels in chronic fatigue syndrome. BMC Psychiatry. 2006 Nov 13;6:53.

      3 Van Houdenhove B, Neerinckx E, Onghena P, Lysens R, Vertommnen H: Premorbid "overactive" lifestyle in chronic fatigue syndrome and fibromyalgia: an etiological relationship or proof of good citizenship? J Psychosom Res 2001, 51:571-6.

      4 Riley MS, O'Brien CJ, McCluskey DR, Bell NP, Nicholls DP: Aerobic work capacity in patients with chronic fatigue syndrome. BMJ 1990, 301:953-6.

      (contd.)


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    3. On 2013 Oct 24, Tom Kindlon commented:

      Test of "physical fitness" used seems far from ideal for this cohort

      The authors state in the abstract that "an empirically defined fatigue syndrome 6 months after onset" was associated with "lower physical fitness". "Lower physical fitness" is a term that is regularly used throughout this paper. However, has it been properly defined especially for this post-viral group? And what can be inferred from the correlation?

      Firstly it should be remembered that the study used two measures of physical fitness from the exercise test: What they called "exercise power" was calculated as "the number of stairs climbed, multiplied by the height of each stair, and the participant's weight." A measure of "physical fitness" was calculated by "dividing the number of stairs climbed by the exercise pulse-rate difference". It seems rather arbitrary to ignore the first when mentioning "physical fitness" in the study and abstract.

      It also needs to be pointed out that this is an unusual way to define fitness and may not be suitable for people with CFS and related post-viral syndromes. For example, Postural Orthostatic Tachycardia Syndrome (POTS) has found to be more common in this sort of population than in other populations. A recent study<sup>1</sup> using a standing test of 2 minutes duration found a prevalence rate of POTS of 27% compared to 9% in a control group (p=0.006). A previous case control study of orthostatic intolerance in children/adolescents with chronic fatigue syndrome had found a significant higher rate (p=0.01) POTS without hypotension in the patients with CFS compared to the controls (but no difference of the rate of POTS with hypotension).<sup>2</sup> Other researchers in the field feel POTS is an important issue in the area of CFS, ME and related syndromes.<sup>3</sup> So in the light of these findings it seems questionable that this is a suitable test to test for "physical fitness".

      It should also be remembered that it is not easy to test somebody's fitness when they have an infection - a "fit" person such as (say) a sportsperson can seem unfit if one tests them when they are ill but within a short period of time could be playing sport competitively and generally showing better physical fitness than could be explained by any physical training in the interim.

      References:

      [1] Hoad A, Spickett G, Elliott J, Newton J. Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome. QJM. 2008 Sep 19.

      [2] Galland BC, Jackson PM, Sayers RM, Taylor BJ. A matched case control study of orthostatic intolerance in children/adolescents with chronic fatigue syndrome. Pediatr Res. 2008 Feb;63(2):196-202.

      [3] Spence V & Stewart J (2004) Standing up for ME, Biologist 51(2): 65-70.


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    1. On 2016 Feb 19, E M Martínez-Cáceres commented:

      In the light of the recent PubMed comment by Morten Oksvold, the referenced research study was performed entirely in our research centre by the research team led by Dr. Martínez-Cáceres at the time with Dr. Espejo as predoctoral researcher. Hence, the EAE in vivo experiments were performed in Barcelona with no involvement from Dr. Penkowa, who was engaged as an expert histopathologist. Dr. Penkowa received processed and encoded samples with which she performed some of the histopathological studies. The results were returned to us for overall analysis and submission for publication. It was agreed that Dr. Penkowa would be co-author of the published work.


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    2. On 2016 Feb 01, Morten Oksvold commented:

      Please note that this article is 1 out of 15 publications for which an independent investigation initiated by the University of Copenhagen has found suspicion of scientific dishonesty. The conclusion from the report was published July 23, 2012:

      http://news.ku.dk/all_news/2012/2012.8/indications_of_fraud_in_penkowas_early_research/

      This articles should therefore not be cited.


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    1. On 2016 Jan 23, Daniel Schwartz commented:

      This paper addresses a practical consideration when providing dialysis to a patient with a toxic alcohol ingestion - the need to plan the nursing hours likely needed to run dialysis, which is often in the on-call/overnight period.

      The model has been converted to a web and mobile app based tool to support easier usage: http://qxmd.com/calculate/dialysis-duration-needed-for-methanol-ingestion

      Conflict of interest: Medical Director, QxMD


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    1. On 2014 Jan 08, Brett Snodgrass commented:

      Dear Authors,

      Thank you for the excellent report.

      Is it possible that the fistula might alternatively be described as an unusually prominent vessel of Wearn? These vessels are unusually prominent in PAIVS, probably due to the hypertensive right ventricle.

      http://www.ncbi.nlm.nih.gov/pubmed/23332812

      For additional commentary, please see

      https://twitter.com/BrettSnodgrass1/status/412868120508788736/

      Comments and suggestions are welcome.

      Thank you kindly.


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    1. On 2015 Apr 02, Harri Hemila commented:

      Cochrane review (2001) on vitamin C and asthma by Kaur B, 2001 misled readers for a decade due to the errors in the extraction and analysis of data.

      The Cochrane review (2001) on vitamin C and asthma by Kaur B, 2001 has substantial errors. I found errors in the 2009 update of that review by Kaur B, 2009. My comments of the 2009 update are available as a separate document. Then I found that the errors originated in the first version by Kaur B, 2001, and they were repeated in the updates by Ram FS, 2004 and by Kaur B, 2009, until the review was withdrawn by Kaur B, 2013. Thus the Cochrane review (2001) on vitamin C and asthma misled readers for over a decade due to the errors in the extraction and analysis of data. Here I briefly describe the errors in the first version of the Cochrane review (2001) on vitamin C and asthma by Kaur B, 2001.

      As relevant background knowledge, it was known long before Kaur B, 2001 that exercise can cause exercise-induced bronchoconstriction (EIB or EIA, exercise-induced asthma), eg Mahler DA, 1993, and that respiratory virus infections can cause exacerbations of asthma, eg Nicholson KG, 1993. Thus, if vitamin C influences bronchoconstriction, the effects might be most pronounced during exercise and/or viral infections.

      Errors in the extraction of data

      Kaur B, 2001 wrote in the Results section (p.4): “there were two studies where the protective effects of vitamin C were investigated using exercise challenge. Both these studies reported pulmonary function outcomes, but one (Cohen 1997) reported absolute mean value post-exercise, while the other (Schachter 1982) reported absolute change post-exercise .”

      In Comparison 01: Outcomes 01 and 02 (p. 10), Kaur B, 2001 presented the results of those two studies. However, Cohen HA, 1997 had 20 participants, yet Kaur B, 2001 showed data for only 11 participants, without revealing to the reader that data for 9 of Cohen's participants are missing from their review. Cohen showed the data of 11 participants on the basis that vitamin C was beneficial for them. However, it is inappropriate and violates the ITT principle to show such a biased subgroup in the Cochrane review by Kaur B, 2001, without explaining that another 9 participants were excluded. Cohen HA, 1997 also reported that on the placebo day, 20/20 of the participants had EIB, whereas on the vitamin C day, 10/20 had EIB. This comparison does not need any imputations, but these data were not extracted for the Cochrane review by Kaur B, 2001.

      A decade before the Kaur B, 2001 review, papers reported that “EIA symptoms start after exercise, peak 8 to 15 minutes after exercise” so that there is a delay between the end of exercise and the peak of FEV1 decline, and “a fall of 10% or more in the FEV1 after exercise is diagnostic” so that the relative change in FEV1 (in %) is the most reasonable outcome when assessing EIB, eg Mahler DA, 1993. Such facts are relevant when analyzing EIB trials.

      Kaur B, 2001 considered that “exercise challenge” was a particular issue in the Cohen HA, 1997 and Schachter EN, 1982 studies, see the above extract. However, in Outcome 01 (p.10) the Cochrane review showed data on the pre-exercise FEV1 levels, which is not an outcome influenced by exercise. In Outcome 02 (p.10) the Cochrane review extracted data on the absolute post-exercise FEV1 level for Cohen HA, 1997 and absolute FEV1 change for Schachter EN, 1982. These outcomes are not relevant, since the standard outcome for EIB is the relative change in FEV1 (in %), see above.

      Furthermore, the greatest decline in FEV1 occurs about 8 to 15 min after the end of exercise, above. However, in Outcome 02 (p.10), Kaur B, 2001 shows Schachter's FEV1 changes immediately after exercise in Schachter's Table II, instead of FEV1 changes 5 min after exercise which Schachter reported in Table III. The latter is much more relevant in a study on EIB, since “EIA symptoms ... peak 8 to 15 minutes after exercise”, Mahler DA, 1993.

      Kaur B, 2001 (p.4) write that “Anah did not report data in a manner that permitted further analysis”. However, in the following paragraph, Kaur B, 2001 wrote that, in the Anah study, “there were 9 exacerbations in the intervention group which had 22 patients and 35 exacerbations in the placebo group which had 19 patients ”. Thus, Anah CO, 1980 did report data that can be statistically analyzed, see below.

      Errors in the analysis of data

      Schachter EN, 1982 and Cohen HA, 1997 were cross-over studies so that the same participants were randomly administered vitamin C or the placebo. Such data should be analyzed by the paired t-test.

      In Outcomes 01 and 02 (p.10), Kaur B, 2001 analyzed Schachter and Cohen data by the unpaired t-test, which is unsound for paired data. Kaur B, 2001 reported no difference between the vitamin C and placebo days for 11 of Cohen's participants with P=0.4 (unpaired t-test), whereas the correct paired t-test yields P=0.003.

      Furthermore, given that the goal was to examine the effect of vitamin C on EIB, Kaur B, 2001 should have calculated the relative changes in FEV1 (in %), see above.

      Schachter EN, 1982 published the data for all their 12 participants, and Kaur B, 2001 could have used the paired t-test to analyze the relative changes.

      Similarly, Kaur B, 2001 could have calculated the relative changes for the 11 participants published by Cohen HA, 1997, and could have imputed eg “no effect” for the 9 participants who had missing data.

      Nevertheless, using the paired t-test is a simplistic analysis of FEV1 changes, since it is possible that the effect of vitamin C depends on the severity of EIB. Hemilä H, 2013 analyzed the two studies using linear regression. Schachter EN, 1982 showed a 55% reduction in the postexercise FEV1 decline (95%CI 32% to 78%) with vitamin C. Imputation of “no effect” to the 9 participants with missing data of Cohen HA, 1997 yielded an estimated 42% reduction in the postexercise FEV1 decline (19% to 64%) with vitamin C. Finally, Cohen HA, 1997 also published the EIB status, which has no missing data. On the placebo day, 100% (20/20) of participants suffered from EIB, whereas on the vitamin C day, only 50% (10/20) suffered from EIB. Thus vitamin C caused a 50 percentage point decrease (23 to 68) in the occurrence of EIB, see Hemilä H, 2013.

      Kaur B, 2001 (p. 4) claimed that “Anah did not report data in a manner that permitted further analysis,” which is incorrect. Anah CO, 1980 reported that in the placebo group (n=19), there were 35 asthma attacks, but in the vitamin C group (n=22), only 9 attacks. By using the standard Poisson approach, these data give RR=0.22 (0.09 to 0.47). Anah did not publish the individual level data and it might be over-dispersed, see Glynn RJ, 1996. Nevertheless, Anah published partial descriptions of the asthma attack distributions which can be used to impute more realistic distributions for the treatment groups, yielding a 95%CI of 0.06 to 0.81, which is still far from the null effect, see Hemilä H, 2013. Furthermore, the exact distribution of severe and moderate asthma attacks in the vitamin C group can be inferred from Anah CO, 1980 and this outcome needs few imputations. Vitamin C reduced the incidence of severe and moderate asthma attacks by RR=0.11 (0.02 to 0.48).

      In conclusion, had Kaur B, 2001 extracted data correctly, and had they properly carried out the statistical analysis, they could have concluded in 2001 that there was strong evidence that vitamin C was beneficial against EIB in Cohen HA, 1997 and in Schachter EN, 1982, and against common cold-induced asthma exacerbations in Anah CO, 1980.

      Secondary analysis of the Cohen HA, 1997, Schachter EN, 1982 and Anah CO, 1980 studies has been carried out by Hemilä H, 2013, Hemilä H, 2013, and Hemilä H, 2014.


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    1. On 2015 Jan 08, David Mage commented:

      Jack Finklea, first Director of the EPA Health Effects Research Laboratory, RTP/NC, wrote here as follows: "We should use what we know in preventive programs and in directing future research. We will make some mistakes when we apply incomplete knowledge, but I think that our need for an excellent scientific information base should not mask the need for society to act on what we do know to clean-up the workplace, and environmental pollution."

      The five major mistakes EPA made in setting the first Particulate Matter (PM) National Ambient Air Quality Standard were as follows:

      1) The PM standard was for Total Suspended Particulate (TSP) as measured by a highvol sampler that collected all PM with aerodynamic diameters (AD) ranging up to 40 microns. This included PM too large to be inhaled. It was later revised to reflect only respirable PM that were < 10 um and < 2.5 um AD.

      2) The first PM NAAQS was 75 ug/m3 TSP as a 1-year geometric mean (GM) based on PMID 6017082. This was a major mistake because two values 5 and 5 have an arithmatic mean (AM) of 5 and a GM of 5 but 0 and 10 have an AM of 5 and a GM of 0! But note, the health effect of {0,10} is greater than the health effect of {5,5}. In addition the GM is not relatable to the dose of inhaled PM even if the total volume of air inhaled during the year were known.

      3) The PM NAAQS were, and still are now, based upon the collected mass of the PM, not its molecular composition. From first principles, the cardio-pulmonary toxicity of any PM molecule depends upon its molecular structure and not its molecular weight. Thus if two PM samplers collect the identical number of molecules of the same AD in the same amount of time, EPA would consider the PM collection with the higher average molecular weight to produce more of a health effect (e.g., it is more toxic) than the other collection. This mistake has not been corrected and still underlies virtually all PM studies.

      4) All PM NAAQS are based upon the PM concentration measured at an ambient PM monitoring station location meeting various siting and location criteria. Given that no subject spends 24-hours continuously breathing only the ambient air at the station location, the personal PM exposure of all people living in the area will not be numerically equal to the official ambient PM concentration that EPA compares to the NAAQS.

      5) The PM NAAQS and all PM epidemiology studies upon which it is based assume the PM health effects follow an ambient PM concentration response relation or a personal PM exposure response relation. They follow neither! They must follow a dose response relation with dose given a value with units specific to the health effect under consideration. For instance: i) if the health effect is systemic, then the dose should be reported as mg/kg-day; ii) if the health effect is related to pulmonary airway surface irritation, then the dose should be reported as mg/m2-day where the mg might, for example, refer to the mass of PM deposited on the non-ciliated sensitive area of alveoli of the pulmonary tract, and m2 refers to that area (not the entire area of the pulmonary tract).


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    1. On 2014 Nov 19, Wei Liu commented:

      After a long 20 years, the results are confirmed by another scientist Michael Bailey.


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    1. On 2017 Jun 08, Monica Green commented:

      There is a typographical error in this entry (PMID: 11624264). The title of the study should correctly read: In search of an "Authentic" women's medicine: the strange fates of Trota of Salerno and Hildegard of Bingen.


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    1. On 2017 Feb 10, Romain Brette commented:

      Dear authors,

      I am very disappointed and rather surprised by the tone of your reply, and even more surprised by your final reflections. You consider that one should not post comments publicly. But to post comments and let authors reply is the whole point of PubMed Commons. It is not clear to me what harm is done to science since the authors's responses are published; on the contrary. There is no reason to be aggressive when discussing with a peer.

      Best regards, Romain Brette


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    2. On 2017 Feb 10, David Attwell commented:

      The answers to Dr Brette’s new points are as follows.

      (1a) Ohmic vs Goldman dependence of current on voltage

      For a cell as assumed in Attwell & Laughlin (2001) (i.e. 200 Megohm membrane measured with a 10mV hyperpolarizing step, VNa=+50mV, VK=-100mV, Vrp=-70mV, [Na]o=[K]i=140mM, T=37C), assuming a Goldman voltage dependence for the Na<sup>+</sup> and K<sup>+</sup> fluxes through ion channels leads to PNa/PK=0.0746 and a Na<sup>+</sup> influx at the resting potential of 130pA, corresponding to an ATP consumption of 2.7x10<sup>8</sup> molecules/sec. This is 21% less than the 3.42x10<sup>8</sup> molecules/sec we calculated using an ohmic dependence of the currents on voltage. This difference is negligible given the variation of measured input resistances and the range of other assumptions that we needed to make. Furthermore, there are no data establishing whether the voltage-dependence of Na+ influx is better described by an ohmic or a Goldman equation.

      (In a later post Dr Brette claims that the error arising is 40%. We suspect that his value arises from forgetting the contribution of the Na/K pump current to setting the resting potential, which leads erroneously to PNa/PK=0.05, and a 41.3% lower value than the ohmic dependence predicts.)

      (1b) Cl<sup>-</sup> permeability

      Our point was that the Cl<sup>-</sup> permeability was negligible. Which equation was used to derive that fact is therefore irrelevant.

      (2) Pumps

      We still disagree with the notion that, for a membrane with just Na<sup>+</sup> and K<sup>+</sup> fluxes, the system is unstable if it only has a Na/K pump. The Na pump rate is adjusted to match activity via its dependence on [Na<sup>+</sup> ]i and by the insertion of more pumps when needed.

      (3) Cost of Na<sup>+</sup> extrusion at the mean potential

      Tonic synaptic activity may depolarize cells by a mean value of ~4-8mV (Paré et al., 1998, J Neurophysiol 79, 1450). This will affect the calculation of “resting” Na+ influx negligibly (e.g. by ~6mV/120mV = 5% for a 6mV depolarization with Vrp=-70mV and VNa=+50mV). As stated in our earlier comment, this depolarization does not affect the ATP used per Na<sup>+</sup> pumped by the Na/K pump. Finally the ATP used on extruding synaptic ion entry is considered separately in the calculations.

      (4) What input resistance tells us

      For cortical L2/3 pyramidal cells the majority of the membrane area is in the basal dendrites, which have an electrotonic length of ~0.24 space constants, while the apical dendrites have an electrotonic length of ~0.69 space constants (mean data at body temperature from Trevelyan & Jack, 2002, J Physiol 539, 623). Larkman et al. (1992, J Comp Neurol 323, 137) similarly concluded that most of the dendrites of L2/3 and L5 pyramidal cells were within 0.5 space constants of the soma.

      Elementary cable theory shows that, for a cable (dendrite or local axon) with a sealed end, with current injection at one end, the ratio of the apparent conductance to the real conductance, and thus the ratio of our calculated ATP usage (on Na<sup>+</sup> pumping to maintain the cable’s resting potential) to the real ATP usage, is given by (1/L).(exp(2L) - 1)/(exp(2L) + 1) where L is the electrotonic length (cable length/space constant). For L=0.24, 0.5 and 0.69, respectively, this predicts errors in the calculated ATP use of 1.9%, 7.6% and 13.3%, which are all completely negligible in the context of the other assumptions that we had to make.

      For the axon collaterals near the soma, there is less information on electrotonic length, but the few measurements of axon space constant that exist (Alle & Geiger, 2006, Science 311, 1290; Shu et al., 2006, Nature 441, 761) suggest that the axon collaterals near the soma will similarly be electrically compact and thus that their conductance will be largely reflected in measurements of input resistance at the soma. We excluded the part of the axon in the white matter from our analysis, but did include the terminal axon segments in the grey matter (where the white matter axon rises back into a different cortical area. Re-reading after 16 years the source (Braitenberg & Schüz, 1991, Anatomy of the Cortex, Chapter 17) of the dimensions of these axons, it is clear that those authors were uncertain about the contribution of the terminal axon segments to the total axon length, but assumed that they contributed a similar length to that found near the soma in order to account for the total axon length they observed in cortex. It is unlikely that these distant axon segments will contribute much to the conductance of the cell measured at the soma but, partly compensating for this, part of the axon in the white matter will. This, along with the electrical compactness of the dendrites and proximal axons discussed above, implies that our calculated ATP use on the resting potential is likely to be correct to within a factor of 1/f = 1.57 (where f=0.64 is the fraction of the cell area that is electrically compact [ignoring the minor voltage non-uniformity quantified above], i.e. the soma, dendrites and proximal axons, calculated from the capacitances in Attwell & Laughlin and assuming that the proximal axons provide half of the total axon capacitance in the grey matter).

      In fact the situation is likely to be better than this, because this estimate is based on membrane area, but ATP use is proportional to membrane conductance. Estimated values of the conductance of axons (Alle & Geiger, 2006, Science 311, 1290) suggest that the specific membrane conductance per unit area in axons is significantly lower than that in the soma and dendrites (see the Supplementary Information section on Granule Cells in Howarth et al. (2010) JCBFM 30, 403), which reduces the ATP used on maintaining the resting potential of axons.

      General reflections on what people expect from the Attwell & Laughlin paper

      Our paper tried to introduce a new way of thinking about the brain, based on energetics. Given the large number of assumptions involved it would be a mistake to expect individual values of ATP consumption to be highly accurate. Remarkably, the total energy use that we predicted for the grey matter turned out to be pretty well exactly what is measured experimentally. Nevertheless, constant updating of the assumptions and values is, of course, essential. It is interesting that the value we derived for the ATP used per cell on the action potential (3.84x10<sup>8</sup> ATP) was initially revised downwards nearly 4-fold in the light of papers showing less temporal overlap of the voltage-gated Na<sup>+</sup> and K<sup>+</sup> currents than occurs in squid axon (Alle et al., 2009, Science 325, 1405), but has increased with more recent estimates back to be close to our original estimate (3.77-8.00x10<sup>8</sup> ATP, Hallermann et al., 2012, Nature Neuroscience 15, 1007).

      The most important assumption that we made was that all cells were identical, which immediately implies that this can only be an approximate analysis. We were very happy that the total energy use that we predicted from measured ionic currents, cell anatomy and cell densities was so close to the correct value.

      General reflections on post-publication peer comments

      We believe that if someone has questions about a paper then the most productive way to get them answered is: (i) to think about the issues; if that fails (ii) to write to the authors and ask them about the questions, rather than posting some vague and erroneous comments that will forever be linked to the paper, regardless of their validity; and if that fails (iii) to write a paper or review which goes through peer review, pointing out the problems. Peer review is crucial for determining whether the points are valid or not - it potentially saves many readers the time needed to read possibly erroneous comments.

      It takes a long time to reply to such comments, and we feel that Dr Brette could have done the calculations that we have provided in our two sets of responses. We will not be posting further responses therefore.

      David Attwell & Simon Laughlin, 09-02-17


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    3. On 2017 Feb 08, Romain Brette commented:

      A qualification about point (2): I agree it is theoretically possible to use a single 3:2 Na/K pump and have a stable system, if firing rate is lower than a limit set by the minimum voltage at which the pump can work (from thermodynamic considerations). In this case, it is probably ok to neglect the other pumps (assuming chloride does not play a role); at least the model is consistent. As I wrote in my initial comment, point (4) seems to be the more problematic point. Point (1a) leads to a correction of about 40%.


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    4. On 2017 Feb 01, Romain Brette commented:

      Thank you very much for your detailed reply. I obviously sympathize with the idea that theoretical work requires simplifying assumptions. The question is to what extent these simplifications lead to accurate estimates, and I disagree that the number of citations is a good indicator of this point.

      Here is a more detailed analysis. I will respond starting from the last point, as it will hopefully be clearer.

      (4) What input resistance tells us

      Thank you for pointing to your more recent studies. It still remains that the assumption “that input resistance measured at the soma can give us a rough estimate of ATP use on the resting potential” cannot be correct here. I am simply using the numbers given in the paper (Attwell & Laughlin 2001), in particular in section “Energy needed for action potentials”, where it is considered that the typical unmyelinated axon has length 4 cm and diameter 0.3 µm. This means that most of the axon’s length is beyond the characteristic length of voltage attenuation (not more than a few hundred µm) and so the input resistance at the soma does not include the axon. But the membrane area of the axon is many times that of the soma, again according to the numbers used in this paper. One can simply divide the charge needed to depolarize the axon by the charge needed to depolarize the soma, as given in the text: 3.77 x 10<sup>-11</sup> / 1.96 x 10<sup>-12</sup> = about 20. So the membrane resistance (1/total conductance) should be about 20 times lower than measured at the soma. One may argue that the input resistance at the soma also includes part of that of the dendrites. But the total dendritic area is (following the numbers given in the paper) 1/3 of that of the axon, so even if we include all of it (very conservative), we still find that the membrane resistance is overestimated by a factor 3. So one needs to apply a correction factor of 3-20 (3 being very conservative).

      (3) Cost of Na+ extrusion at the mean potential

      I am afraid I was not clear enough. I was referring to a much more elementary point, which is that the fluxes of Na+ and K+ depend on the membrane potential, since the ionic currents depend on the membrane potential (at least through the driving force). With synaptic activity, the membrane potential is typically depolarized because of the mean synaptic current. So the balance of currents used in the methods should include the total current Isyn + INa + IK, in addition to the pump current. Unfortunately we have now three unknowns for two observables (input resistance and mean potential).

      (2) Pumps

      Again I apologize that my comment was apparently not clear. In a system with a single pump with 3:2 stoechiometry, equilibrium can only be achieved if the mean flux of Na+ through the channels exactly equals 3/2 of the mean flux of K+. This can only happen at a very specific potential; so the pump can only do its job around one particular membrane potential value. If the neuron is depolarized by synaptic activity, for example, the pump fails to maintain equilibrium (too much K+ leaking out). Finally it can also be seen that, because each action potential produces an equivalent flux of Na+ and K+ (electroneutrality), i.e. with 1:1 stoechiometry, a single 3:2 pump cannot maintain equilibrium at high activity.

      To compensate for arbitrary fluxes of n ions, one needs to modulate the activity of at least n pumps. In a Na/K system, theoretically a second Na/K pump with a different stoechiometry would work. Alternatively, one can use two additional cotransporters which carry Cl- in opposite directions together with K+ and/or Na+ (eg NKCC1 + KCC2). In such a system, the Na/K pump is used not only to compensate for Na+ flowing into the ionic channels, but also to provide energy for the other pumps in the form of the Na+ gradient. In any case, ensuring ionic equilibrium independently of activity (input or output) requires at least two pumps, and unfortunately this makes it impossible to estimate their activity from just the knowledge of input resistance and mean/resting potential.

      (1a) Ohmic vs Goldman-Hodgkin-Katz dependence of current on voltage.

      I agree that using a linear model is more convenient. My point was rather that it is not accurate. It should be recalled that the linear (or “ohmic”) model of ionic currents has no biophysical basis (in contrast with GHK, which is based on a biophysical model, although indeed a simple one). It was derived empirically by Hodgkin & Huxley in the squid axon. However in the same preparation, Hodgkin and Katz (HODGKIN AL, 1949) have shown that the resting potential is better predicted by the GHK equation.

      (1b) Cl- permeability.

      Thank you for these references, it is very helpful. Note however that to show that chloride permeability is low, Xu and Adams used indeed the GHK equation, not the ohmic equation. Note also that all the points I have made above still apply to a Na/K system.

      Summary

      In summary, these different points make it unlikely that it is possible to estimate Na+ fluxes from just the knowledge of input resistance (especially at the soma) and resting (or mean) potential. One would rather need estimates of K+ and Na+ currents at the mean potential (eg from patch-clamp measurements).


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