On 2013 Dec 24, Kenneth Witwer commented:

Following the link to the VMir download results in a "Seite nicht gefunden" (page not found) error. Is there a new site, or is there an error in the published URL?

On 2013 Oct 22, Jonathan Eisen commented:

I am the senior author of this paper and I wrote a detailed blog post about the "Story behind the paper" that may be of interest. See http://phylogenomics.blogspot.com/2011/03/story-behind-story-of-my-new-plosone.html.

On 2015 Aug 11, Lydia Maniatis commented:

The claim that this study controlled for shape is incorrect. The contour elements making up the "patterned rectangles" referred to in the abstract did have a shape, and this shape was perfectly confounded with the factor of "entropy." The elements in the "low entropy" figures had squared-off, rectangular, edges, while the elements in the "high-entropy" figures had non-rectangular, slanted edges. Inferring an occlusion allows their shape to be regularised.

On 2016 Apr 07, Dr. Kam Cheong Wong commented:

There are various methods that can be applied to generate inputs for an Ishikawa diagram such as focus group discussion, review of process-flow, survey, interview, literature review, brain storming, and failure mode and effects analysis (FMEA).

FMEA is an engineering methodology in origin. It can be modified and applied to provide inputs into an Ishikawa diagram via team work or self-directed learning. The human biliary system was used to illustrate a modified FMEA (in short, mFMEA) in an editorial paper which can be accessed via: http://jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-016-0850-6

On 2014 Jul 25, Jens Staal commented:

The VRPR experiment was unfortunately not the best verification that we could have done. In a later experiment, we silenced the uncleavable CYLD in our stable Jurkat cells with siRNA and could restore JNK activation to levels equal to that of normal Jurkats silenced for CYLD, providing further proof that the uncleavable CYLD is indeed causing the JNK inhibition and that it is not a clonal effect.

On the other hand, later results indicate that MALT1 protease activity is not required for JNK activation so the most likely explanation for our observations is that they are visible thanks to the overexpression of CYLD (both WT and R/A are overexpressed to the same extent so the difference is cleavage-dependent) whereas the effect is not visible when expressed at endogenous levels.

On 2015 Feb 19, Devon Ryan commented:

In the off-chance that someone else comes across this paper and wonders why exactly they chose a bonferroni-adjusted p-value threshold of 1.81e-6, it's presumably because that turns out to be a benjamini-hochberg adjusted p-value threshold of 0.05 for maternal age in their microarray dataset. I have no clue why they didn't just say that in their methods.

On 2014 Oct 10, Martin Turner commented:

Would the authors care to report the limits of agreement between the Tonosafe and standard Goldmann prisms? Thank you.

On 2014 May 05, Madhusudana Girija Sanal commented:

1) Provides evidence for the endosymbiotic theory on the origin of mitochondria 2) It says it is possible to make transgenic higher animals with photosynthetic ability (limited by the available body surface area) 3) It shows the adaptability of an organism to foreign genes and gene products through co-evolution 4) It shows the capability of embryonic cells to accept foreign genes and gene products and opens the possibility for wonderful 'compound organisms' Is there any evidence of genetic exchanges between the genomes of the salamander and the alga? It would be nice to do a whole genome sequencing of the salamander and alga and compare with the closest neighbors and relatives (species) to understand the depth of co-evolution.

On 2015 Jun 24, Spencer Bliven commented:

The URL for Mattbench has changed. The current (2015-06) URL is http://bcb.cs.tufts.edu/mattbench

On 2017 Oct 05, Jason Snyder commented:

Doesn't the majority of dentate granule cells express calbindin? And yet there are only ~20 calbindin+ cells per dentate gyrus slice (fig 4).

On 2017 Oct 11, Joe Herbert commented:

A recent paper (Hosp JA, Strüber M, Yanagawa Y, Obata K, Vida I, Jonas P, Bartos M.

Hippocampus. 2014 24:189-203.) says 24% . But I can't see this is very relevant to the major thrust of the paper.

On 2014 May 15, G L Francis commented:

In setting out to produce a simplified chemically defined culture medium for human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) the authors demonstrated removal of bovine serum albumin (BSA) and other constituents was possible. By judicious screening the resultant optimized medium (E8) was greatly simplified compared to the starting medium (TeSR) and provided comparable outcomes for long term undifferentiated proliferation of both human ESCs and iPSCs.

The authors appear to show quite convincingly that in the original TeSR medium BSA serves the purpose of neutralizing the potential toxicity of β-mercaptoethanol (BME) (see Fig 1 : Title. ‘’Albumin is not required for hESC culture’’). The only question I raise is about the veracity of the overall conclusion is that albumin presence in the absence of BME does not enhance the proliferation (I assume equals combined survival of plated ESCs and subsequent proliferation) measured at 120h after plating in TeSR-based medium, as depicted in Fig.1 panel (f).The first bar in Fig.1 panel (f) representing the activity for ‘’complete TeSR medium (with BSA & BME)’’, is stimulated a further two- fold in the ‘’without BME’’ medium (presumably with BSA!) represented in the last bar of that panel (f). If that is the case, does that not indicate that addition of albumin significantly improves the performance of the medium in the long term proliferation of hESCs – apparently at odds with the conclusions argued in the Discussion of the paper?

Moreover, in Figure 2 titled “Essential medium components for human ESC survival and proliferation” in panel (c) the improvement in proliferation at 129 h for plated hESCs over the starting TeSR medium by a number of additions to a base E8 medium was only 40% (compare this to the improvement of TeSR by TeSR –BME+BSA above in Fig.1). Admittedly the further addition of other components, and finally Nodal, led to incremental improvement over the base components of E8.

I understand the importance of eliminating an animal or human sera sourced component (also what about the transferrin?) This still prompts the question as what would have been the result if albumin was added to the final E8 medium in terms of long term proliferation of hESCs in this study. For the experimental evaluation of this question the best performing batch of BSA would have been most appropriate, however, to address the issues raised about the use of this xenobiotic material, a human recombinant source of albumin could have been evaluated. Human recombinant albumin is now produced at scale under GMP conditions and I believe the price has become more acceptable - I agree the final acceptance of that would rely on a cost benefit analysis at the process level.

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT0094398. We believe the correct ID, which we have found by hand searching, is NCT00944398.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2015 Feb 04, Alberto Halabe Bucay commented:

In this article is cited in the references my work regarding treatment of cancer with citric acid (citrate) published in PubMed since March, 2007: PMID: 17368752.

On 2014 Jan 11, I-Chen Tsai commented:

Wow. PubMed now opens for comments!

On 2013 Oct 21, John Boothroyd commented:

I find this an extremely exciting paper and one of the most important in Toxoplasma epidemiology in the past decade. For years, there has been debate about what fraction of toxoplasmosis infections in humans stems from ingestion of oocysts (in drinking water or on soil-contaminated food) vs. tissue cysts (in under-cooked meat, etc.). But until this paper, there was no way to do more than guess. Here, the authors report very exciting data showing that antibodies to an oocyst (sporozoite) protein are elicited and detectable in oocyst-initiated infections in animals and humans. Further work will be needed to determine how reliable it is but all the indications are that it is, in fact, a good predictor of oocyst-initiated vs. tissue-cyst-initiated infections. The results to follow could alter the public health message in very important ways and allow advice to be targeted to the most risky activities.

On 2014 Jun 21, Ivan Oransky commented:

This paper has been retracted: http://retractionwatch.com/2014/06/20/if-it-smells-like-pig-sh-it-probably-is-pig-sh-a-stinky-retraction/

On 2014 Nov 23, Harri Hemila commented:

A comment is available at: https://helda.helsinki.fi/handle/10138/228058

On 2016 May 02, Riccardo Polosa commented:

Evidence that activation of the haemo-coagulative system occurs in COPD is accumulating with potential implications for cardiovascular disease (CVD)(1,2). Maclay and colleagues(3) have recently reported a significant but small increase in platelet activity by flow cytometric analysis of circulating platelet-monocyte aggregates in COPD patients. This does not seem to be strongly supportive of this view as the observed changes are well within test repeatability and mainly due to a handful of outliers. Moreover, no changes were reported for the well characterised platelet activation marker, P-selectin.

Although small sample size, co-morbidities and medications may have contributed to these largely negative findings, an important factor to be considered is smoking. Of note, the authors excluded active smokers from COPD patients and included a control group of smoking habit- (i.e. ≥10 pack/yrs; at least 6 months tobacco abstinence) and age-matched ex-smokers with no respiratory symptoms. However, as for several biomarkers of systemic inflammation (e.g. C-reactive protein)(4), airway inflammation (e.g. sputum neutrophilia)(5), and clotting activation (e.g. D-Dimer and prothrombin fragment 1+2)(6), elevation in markers of platelet activation may persist for many years after smoking cessation, reflecting that the underlying damage caused by smoking takes a protracted time to recover. Thus, the baseline level of platelet activation in the control group may not be truly representative. Future studies should recruit either lifetime non-smokers or ex-smokers who have been abstinent for 3-5 years as controls.

Assuming that platelet activation is significant in COPD, it is highly speculative to suggest that such mechanisms are associated with increased risk of CVD in COPD. Firstly, measurements of platelet activation in smoking-related conditions may not be that efficient in predicting cardiovascular mortality and morbidity. Secondly, platelet activation is not disease specific (can occur in degenerative, inflammatory and smoking-related diseases) and may be due to immobilization during hospitalization. A control group for this confounder was not included in the exacerbation study. Thirdly, although systemic inflammation may be responsible for platelet activation, we cannot discount a role for the underlying tissue/cellular injury that persists for many years after smoking cessation(4-6). Specifically, the source of systemic inflammation (± platelet activation) in COPD may not necessarily be associated with activation/injury of the airway epithelium. Alternatively, direct spill-over of pro-inflammatory mediators and potent platelet activators in the bloodstream can be traced to the vascular endothelium, which are metabolically activated on smoke exposure(7,8). Lastly, it is unclear whether the low-grade systemic inflammation reported in COPD has an independent causal role in cardiovascular co-morbidities(9). CVD is known to occur long before the onset of COPD and is known to be strongly associated with cigarette smoking. Conclusive evidence of systemic inflammation contributing to greater risk of CVD requires large well-controlled long-term prospective studies normalized for intensity and duration of smoking.

References

1. Wedzicha JA, Syndercombe-Court D, Tan KC. Increased platelet aggregate formation in patients with chronic airflow obstruction and hypoxaemia. Thorax. 1991;46(7):504-7.
2. Polosa R, Malerba M, Cacciola RR, Morjaria JB, Maugeri C, Prosperini G, et al. Effect of acute exacerbations on circulating endothelial, clotting and fibrinolytic markers in COPD patients. Intern Emerg Med. 2011. Epub 2011/06/11.
3. Maclay JD, McAllister DA, Johnston S, Raftis J, McGuinnes C, Deans A, et al. Increased platelet activation in patients with stable and acute exacerbation of COPD. Thorax. 2011;66(9):769-74.
4. Yanbaeva DG, Dentener MA, Creutzberg EC, Wesseling G, Wouters EF. Systemic effects of smoking. Chest. 2007;131(5):1557-66.
5. Willemse BW, ten Hacken NH, Rutgers B, Lesman-Leegte IG, Postma DS, Timens W. Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers. Eur Respir J. 2005;26(5):835-45.
6. Caponnetto P, Russo C, Di Maria A, Morjaria JB, Barton S, Guarino F, et al. Circulating endothelial-coagulative activation markers after smoking cessation: a 12-month observational study. Eur J Clin Invest. 2011;41(6):616-26.
7. Cacciola RR, Guarino F, Polosa R. Relevance of endothelial-haemostatic dysfunction in cigarette smoking. Curr Med Chem. 2007;14(17):1887-92.
8. Guarino F, Cantarella G, Caruso M, Russo C, Mancuso S, Arcidiacono G, et al. Endothelial activation and injury by cigarette smoke exposure. J Biol Regul Homeost Agents. 2011;25(2):259-68.
9. Morjaria JB, Polosa, R. The holistic perspective of chronic obstructive pulmonary disease: doubt some more. Ther Adv Chronic Dis. 2010;1(2):37-41.

On 2014 Feb 27, George W Hinkal commented:

The National Cancer Institute has been investing in the development of an online webportal of curated cancer nanotechnology data called caNanoLab. The numerical data, nanomaterial characterizations and composition information for the two nanoparticles related to this publication have been added to the database and can be found at:

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=37191682&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=37191683&page=0&tab=ALL

The left navigation links on these pages provide information about each sample (under Navigation Tree).

For general information on how to use caNanoLab, please visit https://cananolab.nci.nih.gov/caNanoLab/home.jsp

On 2014 Mar 12, George W Hinkal commented:

None

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT0083283. We believe the correct ID, which we have found by hand searching, is NCT00832832.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2013 Oct 31, John Cannell commented:

The authors stated that markers of oxidative stress are present in autism spectrum disorder (ASD). I wonder if the authors are aware that the genes for the antioxidants superoxide dismutase and thioredoxin reductase are directly up-regulated by the secosteroid 1,25 di-hydroxy vitamin D3 (calcitriol). I believe both genes also harbor a vitamin D response element.

Peehl DM, Shinghal R, Nonn L, Seto E, Krishnan AV, Brooks JD, Feldman D. Molecular activity of 1,25‐dihydroxyvitamin D3 in primary cultures of human prostatic epithelial cells revealed by cDNA microarray analysis. J. Steroid Biochem Mol. Biol 2004;92:131–141. PMID:15555907>

Calcitriol also directly up-regulates glutathione reductase and increases glutathione levels.

Jain SK, et alo. Vitamin D upregulates glutamate cysteine ligase and glutathione reductase, and GSH formation, and decreases ROS and MCP-1 and IL-8 secretion in high-glucose exposed U937 monocytes. Biochem Biophys Res Commun. 2013 Jul 19;437(1):7-11. doi: 10.1016/j.bbrc.2013.06.004. Jain SK, 2013

Also, supplemental vitamin D significantly reduces oxidative stress in humans.

Nikooyeh B, et al. Daily intake of vitamin D- or calcium-vitamin D-fortified Persian yogurt drink (doogh) attenuates diabetes-induced oxidative stress: evidence for antioxidative properties of vitamin D.J Hum Nutr Diet. 2013 Jul 5. doi: 10.1111/jhn.12142. Nikooyeh B, 2014

Asemi Z, et al. Vitamin D supplementation affects serum high-sensitivity C-reactive protein, insulin resistance, and biomarkers of oxidative stress in pregnant women. J Nutr. 2013 Sep;143(9):1432-8. doi: 10.3945/jn.113.177550. Asemi Z, 2013

Thus the vitamin D theory of ASD (vitamin D deficiency being the environmental risk factor for this highly heritable disorder) is consistent with the authors work. Three recent studies, using community controls, have found 25(OH)D levels are significantly lower in children with ASD. Two of the studies below (Mostafa et al and Gong et al) also found ASD severity, as rated on standard ASD rating scales, is inversely correlated with 25(OH)D levels. Mostafa et al found an R value of -.86 for the association of serum 25(OH)D with ASD severity.

Gong ZL, Luo CM, Wang L, Shen L, Wei F, Tong RJ, Liu Y. Serum 25-hydroxyvitamin D levels in Chinese children with autism spectrum disorders. Neuroreport. 2013 Oct 1. Gong ZL, 2014

Meguid NA, Hashish AF, Anwar M, Sidhom G. Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in Egyptian children with autism. J Altern Complement Med. 2010 Jun;16(6):641-5. Meguid NA, 2010

Mostafa GA, Al-Ayadhi LY.Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity. J Neuroinflammation. 2012 Aug 17;9:201. Mostafa GA, 2012

There is a plethora of basic science explaining why low gestational or early childhood 25(OH)D levels would adversely effect brain development.

Eyles DW, Feron F, Cui X, Kesby JP, Harms LH, Ko P, McGrath JJ, Burne TH. Developmental vitamin D deficiency causes abnormal brain development. Psychoneuroendocrinology. 2009 Dec;34 Suppl 1:S247-57. doi: 10.1016/j.psyneuen.2009.04.015. Epub . Review. Eyles DW, 2009

DeLuca GC, Kimball SM, Kolasinski J, Ramagopalan SV, Ebers GC. Review: the role of vitamin D in nervous system health and disease. Neuropathol Appl Neurobiol. 2013 Aug;39(5):458-84. doi: 10.1111/nan.12020. DeLuca GC, 2013

Eyles DW, Burne TH, McGrath JJ. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol. 2013 Jan;34(1):47-64. doi: 10.1016/j.yfrne.2012.07.001. Epub 2012 Jul 11. Review. Eyles DW, 2013

Furthermore, the vitamin D theory of autism explains most of the epidemiological facts of ASD.

Cannell JJ. On the aetiology of autism. Acta Paediatr. 2010 Aug;99(8):1128-30. Cannell JJ, 2010

Cannell JJ. Autism and vitamin D. Med Hypotheses. 2008;70(4):750-9. Cannell JJ, 2008

70% of American toddlers do not take

On 2017 Jul 07, Wei Wang commented:

Several issues have been raised about this paper on PubPeer. Below are some of the comments:

Comment #1: "Jonathan Warner and colleagues failed to reproduce results reported in this paper. In their paper (PMID: 24860015), Warner et al. state:

"These results are at significant odds with the report that there can be 100-fold differences in the levels of the various RP mRNAs in several tissues of the developing mouse embryo (Kondrashov et al. 2011)."

Comment #3: "The authors wrote:

"Strikingly, we observed tremendous heterogeneity in RP expression among different RPs and within different tissues over a 250-fold range, expressed in log2 space (Figure 7D and Table S3)."

As Jon Warner and colleagues noted, this strikingly tremendous heterogeneity is at odds with any other dataset that we have seen. We downloaded the data from Table S3 and could not reproduce the 250-fold range either. Can the authors explain how they analyzed the data to find the 250-fold range ?

Hopefully, the authors can provide the raw data used for Figure 7D and Table S3.

Maybe some tissues express the mRNAs for all ribosomal proteins at higher levels because they need more ribosomes. Were the transcript data normalized for different global levels of ribosomal protein in different tissues ? "

Comment #4: "In addition to the mentioned issues with this paper, I would like to note some further points. I don't want to discredit the authors, they are certainly working on a very exciting topic, however, this paper makes conclusions and over interpretations, which are by no means proven by the data that they present. The authors claim to "uncover an important role for RPL38 in transcript-specific translational control". However, there are several important concerns with that claim:

(1) The authors don't provide any evidence that the ribosomes in the tissues/cells they are using are lacking RPL38, hence any assumptions about RPL38 specifically regulating the translation of these certain Hox mRNAs are purely speculative.

(2) As "evidence" that the translational defect of these mRNAs is specific to RPL38 deficiency, the authors present figure 4Q, where they are using additional mouse mutants. However, no data are provided to present how much the levels of the respectively affected ribosomal protein in the mutants are actually affected in the used tissues. Furthermore, out of the 8 Hox mRNAs, whose translation is impaired with RPL38 deficiency, the authors test the protein levels only for one (HoxA5) of these 8 transcripts in the additional mouse mutants, this seems like this was picked on purpose. And even for that 1 Hox protein, the data seem questionable. The RPS19 mutant seems to have also reduced HoxA5 protein levels when I look at the western, suggesting that the translational defect is not specific to RPL38 deficiency. The westerns for the other mutants seem to be slightly overloaded in the mutant samples compared to controls, hard to make a conclusion there.

(3) The polysome profiles in figure 3b are more than questionable. The polysomes are basically just a flat line, any quantitative data from RT-qPCR from isolated RNA of these polysomes don’t seem really reliable in terms of translation. Also, it appears hard to believe that the authors were able to dissect selectively the somites without including non-affected tissue material. "

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT00314575. We believe the correct ID, which we have found by hand searching, is NCT00314574.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2014 Jul 25, Prof.Dr.Jogenananda Pramanik commented:

The effects of noise on sleep and their potential harmful repercussions on cardiac patients in hospitals"

Invited Co-Authors: Dr.Saurabh Kole, MBBS.Dip Card.MD.Cardiologist,Belle Vue Clinic, Kolkata,India;and Tanu Pramanik, Lecturer (Clin.Psychology), Allianze University College of Medical Sciences, 13200-Penang, Malaysia.

The author of the current paper (1) deserve applause for timely evaluation of the effects of sound pollution on hospitalized cardiac patients. The World Health Organization guidelines say that for a good sleep, sound level should not exceed 30 dB(A) for continuous background noise, and 45 dB(A) for individual noise events.(2,3) The effect of noise on sleep, however, not only depends on the acoustical parameters of noise but also on the individual as there is large variance in the experience of a person with a particular noise. Personal characteristics such as personality traits, diurnal type, age and self-estimated sensitivity to noise are important individual factors.(4) These autonomic responses to noise during sleep can be obtained for much lower peak noise intensities as during wake states. These effects, mainly involving increased heart rate and vasoconstriction, have been found to habituate over successive noise-exposed nights as opposed to long exposure times. This could indicate an effect on cardiovascular response over the long term exposure. (5) During sleep, heart rate is related to changes in the parasympathetic-sympathetic balance with an increase in sympathetic tone associated with activation and with electroencephalogram (EEG) arousal. Catecholamine levels and sympathetic activity decrease during sleep. So, as one might assume that decreased sleep is associated with increased sympathetic activity and as a result increased blood pressure and heart rate. This association has been observed not only with sleep deprivation but also with regard to sleep disruption. Brief awakenings from sleep for only a few seconds are associated with temporary elevation in blood pressure and heart rate that results from an autonomic reflex.(6) Noise that prevents or interrupts sleep is a nearly universal complaint of patients who are hospitalized (1,2) However, no previous record of systematic research or published report from developing countries like ours is available till date.

The causal relationships between noise exposure, effects on sleep, and contribution to health disturbances, both behavioral and physical, are not firmly established yet. Therefore, we designed current research proposal with a well-defined objective to study noise induced repercussions on cardiac patients in a hospital setting. During our study, we will use EEG, EKG, polysomnogram and other monitoring systems for the patients selected under stringent criteria set by the clinical research committee and University ethical committee. Our research may reveal adequate experimental data to substantiate noise induced repercussions on cardiac patients which may enlighten hospital authorities to be more cautious to protect vulnerable patients from sound pollution.

References: 1. Babisch W.: Cardiovascular effect of noise :Noise Health. 2011 May-Jun;13(52):201-4. doi: 10.4103/1463-1741.80148.

2.Sleep Disruption due to Hospital Noises: Ann Intern Med. 7 August 2012;157(3):1-32 3. Berglund B, Lindvall T, Schwela DH. Guidelines for Community Noise. World Health Organization 1999. Available from: http://www.who.int/docstore/peh/noise/guidelines2.html . [Accessed on 2010 March 28].<br> 4.Muzet A, Weber LD, Di Nisi J, Ehrhart J. Comparison of cardiovascular reactivity to noise during waking and sleep. National Center for Scientific Research Center for Bioclimatic studies. Convention No 82243, 1985.

5.Muzet A, Ehrhart J, Eschenlauer R, Lienhard JP. Habituation and age differences of cardiovascular responses to noise during sleep. In Sleep 1980;212-5.<br> 6.Sforza E, Chapotot F, Lavoie S, Roche F, Pigeau R, Buguet A. Heart rate activation during spontaneous arousals from sleep: Effect of sleep deprivation. Clin Neurophysiol 2004;115:2442-51.

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT0110743. We believe the correct ID, which we have found by hand searching, is NCT01107431.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2016 Sep 21, Morten Oksvold commented:

There is an interesting Brief Communication letter which is questioning the role of BID in NOD signaling (Nachbur U et al., 2012). Please see link:

http://www.nature.com/nature/journal/v488/n7412/full/nature11366.html

In the communications arising, Yeretssian et al., have a reply:

http://www.nature.com/nature/journal/v488/n7412/full/nature11367.html

Yeretssian et al. have even a correction to their reply, due to the fact that they removed several data points from a figure generated by the authors of the original Brief Communication (Nachbur U et al., 2012). Please see link:

http://www.nature.com/nature/journal/v491/n7426/full/nature11668.html

On 2015 Mar 30, University of Kansas School of Nursing Journal Club commented:

University of Kansas School of Nursing Undergraduate Program Team 12: Stacy Hanson, Chelsi Puskas, Shannan Orpin, Sami Johnson, Chandler Schoen, Jen Huynh, and Valerie Melin

Introduction:<br> The purpose of this Journal Club Literature Review was to take a closer look at shared governance by evaluating the functionality Unit Practice Councils through a study by Beverly Fray (2011). Not only did the article create a credible tool for rating this specific hospital’s system, it also obtained important qualitative data that the hospital can use to identify weaknesses in their Unit Practice Councils. This information is crucial for the hospital that this survey serves because this hospital system is on their Magnet journey. This survey is working to fill the gap in knowledge of a credible survey to access functionality of Unit Practice Councils. Our team chose this article after listening to two presentations about Shared Governance from the University of Kansas Hospital and Children’s Mercy Hospital, we were interested on how effectiveness of Shared Governance, specifically Unity Practice Councils, can be measured. We were also interested in this article because it was looking at a hospital system that had not yet achieved Magnet status, unlike the University of Kansas Hospital and Children’s Mercy Hospital. We were interested in a non-magnet status hospital because according to Clavelle, O’Grady, and Drenkard (2013), magnet hospitals have shown to have higher rates of shared governance, resulting in higher levels of nurse-physician relationships and greater positive work environments. Therefore, we were wondering how non-magnet status hospitals approached shared governance.

For this Journal Club Literature Review, we used ProQuest Nursing & Allied Health Source for search for the article. To retrieve this specific article, we typed “shared governance and nurse satisfaction” in the search bar, and then we restricted the search to only include articles that were peer reviewed and published in the last 5 years. This was a descriptive study, describing the Functionality of the Unity Practice Councils and testing the validity of the newly created survey. The target population is Jackson Health System, a health system attempting to achieve magnet status. While Jackson Health System wanted to identify strengths and weaknesses in Unit Practice Councils, they believe that this survey could be used in other hospitals to identify ways to strengthen Unit Practice Councils. This is important because Unit Practice Councils are one of the primary ways that voices are given to nurses, and if the Unit Practice Council is not functioning properly, some of the ideas brought by nurses may not be properly implemented. It is also important because this tool would be able to be used in other hospitals, and weak Unit Practice Council would be able to use strong Unit Practice Councils as resources. Data for the study was collected by surveys based on traits that were observed from highly functional and successful Unit Practice Councils. These surveys results were compared between the Unit Practice Council Coordinator and then the Center for Nursing Excellence.

Findings:<br> The Center for Nursing Excellence and the Unit Practice Council Coordinators reached a 78% concurrence level for functionality of Unit Practice Councils. The study found that 38% of the Unit Practice Councils were low functioning, 22% were middle functioning, and 40% were high functioning. It is also notable to look at what the Unit Practice Councils focus on: 96% focus on improving clinical practice or patient, staff, and physician satisfaction; 92% had invited management to their meetings; 64% use their communication network; and 68% reported being innovative in making tangible improvements at the bedside. While this study was not compared to other settings, the survey would be able to be implemented in other locations to compare the functionality of Unit Practice Councils. The limitations of this study included a low survey response rate and more research needs to be completed to establish reliability of the instrument. Implications: This study is important to nursing because it identifies the functionality of Unit Practice Councils. Because the importance of Shared Governance has been identified, it is important to look at the Unit Practice Council as a source for nursing ideas and empowerment. This survey can be used to identify strength and weaknesses of Unit Practice Councils. The tool is simple enough that it could also be used to measure improvement in Unit Practice Councils, and evaluate nursing practice outcomes. and can be used as objective tool to access quality of Unit Practice Councils. A functional Practice Council can leads to nurse-lead changes on the unit. These changes promote nurse satisfaction and patient-centered care, leading to a positive work environment. Any tool that can promote the higher functioning of Practice Councils is worth studying.

Reference: Clavelle, J., O’Grady, P., Drenkard, K. (2013). Structural empowerment and the nursing practice environment in Magnet organizations. The Journal of Nursing Administration. 43(11), 566-573.

On 2014 Mar 06, Christopher Southan commented:

There is a follow-on paper http://www.ncbi.nlm.nih.gov/pubmed/24204758 that analyses an update of the same data but sliced on a per-year basis

On 2015 Feb 08, Arnaud Chiolero MD PhD commented:

An elegant demonstration of how age could be the only element to consider for the individual primary prevention of CVD

On 2017 May 23, Egon Willighagen commented:

The link to the source code repository no longer exists and now points to this (currently active) repository: https://bitbucket.org/wwmm/chemicaltagger

On 2014 Nov 17, Peter H. Asdahl commented:

The study by Villani et al. addresses the issue of cancer surveillance among TP53 mutation carriers with Li-Fraumeni syndrome. The authors interpreted data from an institutionally-devised cancer surveillance program. Villani et al. concluded that their surveillance approach is feasible, and may lead to a reduction in mortality. In addition, the authors emphasized the importance of genetic testing for early detection. Nonetheless, certain results of the study warrant further discussion.

Villani et al. used an observational design to address their aim, where mutation carriers were given the option of participating in the surveillance or non-surveillance (i.e. standard clinical practice) groups, and were subsequently followed for incident cancers. Given the goal of systematic cancer surveillance, we would expect a higher yield of incident cancers in the surveillance group. Nevertheless, the result from the Villani et al. study contradicts expectation. Specifically, one or more tumors were detected among seven of the 18 (39%) participants who opted for surveillance in contrast to 10 of the 16 participants (63%) who opted for non-surveillance. Given insufficient data in the published report by Villani et al. to estimate person-time contribution for individuals in each group, we assume equivalent follow-up between groups for the purpose of our illustration. Consequently, a patient-level comparison of the two groups yields a 24% reduction in the absolute risk of incident cancers in the surveillance group (risk difference= -24%, 95% confidence interval: -56% to 9%). We would not expect a negative risk difference in this scenario, which raises concerns about potential biases such as healthy user bias or confounding by functional status [1].

Healthy user bias and confounding by functional status are often overlooked but legitimate problems in observational studies of screening effects. For example, if participants in the non-surveillance group had more functional impairments (e.g. related to underlying but undetected cancer) which resulted in opting for standard clinical care rather than systematic surveillance, then eventual detection of underlying cancer in this group may result in a higher yield compared with the surveillance group. Some evidence for this phenomenon may be apparent by the lower than expected survival among participants with incident cancers in the non-surveillance group. In particular, three-year survival among the non-surveillance group was 21%, which is low even for aggressive tumors.

An ideal screening program aims for early detection of cancer with subsequent reduction in cancer-related mortality. Although we do not reject the notion that the screening program in this study detected asymptomatic tumors, the interpretation that the authors’ surveillance program is superior to non-surveillance is not supported by the results. To investigate a possible effect of screening in this population, a more robust study design with random allocation to intervention may be less sensitive to bias.

REFERENCE 1. Shrank WH, Patrick AR, Brookhart MA. Healthy user and related biases in observational studies of preventive interventions: a primer for physicians. J Gen Intern Med. 2011 May;26(5):546-50.

On 2015 Feb 23, MELISSA DAVIS commented:

This cell line is also known as HCC1806

On 2015 Jun 23, Bill Cayley commented:

A great example of when "Less" can be "More": https://lessismoreebm.wordpress.com/2015/06/23/low-cost-mesh-for-inguinal-hernia-repair-in-resource-limited-settings/

On 2014 Feb 27, George W Hinkal commented:

The National Cancer Institute has been investing in the development of an online webportal of curated cancer nanotechnology data called caNanoLab. The numerical data, nanomaterial characterizations and composition information for the nanoparticle related to this publication have been added to the database and can be found at:

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=37191685&page=0&tab=ALL

The left navigation links on this page provide information about each sample (under Navigation Tree).

For general information on how to use caNanoLab, please visit https://cananolab.nci.nih.gov/caNanoLab/home.jsp

On 2014 Mar 12, George W Hinkal commented:

None

On 2016 May 02, Riccardo Polosa commented:

We read with great interest the recent article by Grainge and coll. (1) showing that experimental airway narrowing induced by serial bronchoprovocation testing in patients with asthma may in itself be a stimulus for the development of airway remodelling. These tissue changes were independent of the broncoprovocant used in the study, development of remodelling being equivalent either after allergen or methacholine challenge. Surprisingly, however, the occurrence the characteristic late asthmatic response associated with a progressive fall in FEV1 after allergen (but not methacholine) challenge, failed to produce additional effects in term of enhanced airway remodeling changes in this study.

As for the action of hemodynamic sheer stress in endothelial pathophysiology and atherosclerotic plaque formation (2), it is likely that adaptative wall remodelling in asthma occurs only in response to a brisk mechanical stimulus (as in the severe acute bronchoconstriction of the early asthmatic response), whereas a slow, more progressive fall in FEV1 (as in the late asthmatic response of the allergen challenge) is not able to induce a sufficient stress response for tissue remodeling. Given the wide variability in individual fall in FEV1 and remodelling responses reported in the study by Grainge and coll., it cold have been relevant to investigate a possible correlation between severity of bronchoconstriction and amplitude of remodelling changes. This is important to substantiate these authors speculations.

Remodelling changes in response to bronchoconstriction are not necessarily detrimental, and may have a protective role by stabilizing airway calibre and limiting further narrowing (3). However, in presence of an inflammatory infiltrate and of an intrinsically dysfunctional epithelium – as in asthma (4,5) - mechanotransduction may promote a more harmful form of airway remodelling. To test specificity of the observed effects in asthma, a further study group to control for a non specific effect of bronchoconstriction (by high dose inhaled methacholine) in non-asthmatic individuals would have been highly informative.

Given the relative insensitivity of inhaled corticosteroids in modulating airway remodelling and its progression (6), the search for novel therapies that can specifically reverse or prevent airway remodeling has become an active area for drug development. For the time being, as appropriately pointed out by Grainge and coll., sustained (and safe) bronchodilatation should be recommended more insistently in addition to classical means of disease exacerbation prevention. Unsurprisingly, these considerations may be also valid for patients with chronic obstructive pulmonary disease (COPD).

REFERENCES

1. Grainge CL, Lau LCK, Ward JA, Dulay V, Lahiff G, Wilson S, Holgate ST, Davies DE, Howarth PH. Effect of bronchoconstriction on airway remodeling in asthma. N Engl J Med 2011; 364: 2006-15.
2. Davies PF. Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology. Nat Clin Pract Cardiovasc Med 2009; 6(1): 16-26.
3. McParland BE, Macklem PT, Pare PD. Airway wall remodelling: friend or foe? J Appl Physiol 2003; 95: 426-434.
4. Puddicombe SM, Polosa R, Richter A, Krishna MT, Howarth PH, Holgate ST, Davies DE. Involvement of the epidermal growth factor receptor in epithelial repair in asthma. FASEB J 2000;14: 1362-74.
5. Holgate ST, Polosa R. The mechanisms, diagnosis, and management of severe asthma in adults. Lancet. 2006 Aug 26;368(9537):780-93.
6. Royce RG, Tang ML. The effects of current therapies on airway remodelling in asthma and new possibilities for treatment and prevention. Curr Mol Pharmacol 2009; 2(2):169-81.

On 2015 Jan 30, Zhiyong Lu commented:

Check out our latest developments at: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/MeSHNow/

On 2017 Aug 04, Luis Mauricio T. R. Lima commented:

This is an interesting article showing human amylin and zinc interaction, and the role of His18 in zinc interaction.

We have recently reported that murine amylin can also interact with zinc, and this peptide has no His18, and interaction is mediated by several other contacts, and can result in modulation of the amyloid aggregation process. https://www.ncbi.nlm.nih.gov/pubmed/27693831 http://dx.doi.org/10.1016/j.bpc.2016.09.008

Collectively, these data suggest an universal amyloid behavior of amylin analogues and interaction with zinc, regardless of the presence of proline or His18.

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT0078634. We believe the correct ID, which we have found by hand searching, is NCT00786344.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2014 Jan 20, Tom Kindlon commented:

Things are not clear cut in the CFS field yet

I'm afraid I found the analysis in this paper to be somewhat superficial. In particular, it did not explore why positive statements might not predominate for GET and CBT.

Evidence-based medicine should not just be about efficacy measures but also adverse events. The reporting of harms in trials of CBT and GET for CFS has been recognised as being poor (2,3). As one systematic review pointed out: "There is limited evidence about adverse effects associated with behavioural interventions. Withdrawals from treatment in RCTs suggest that there may be an issue but the evidence is often difficult to interpret because of poor reporting."

A published survey of Norwegian ME/CFS patients found that of 620 who reported their experiences of graded exercise, 488 (78.7%) said that it had caused an overall deterioration (1). Surveys of patients in other countries have also found a high rate of adverse events associated with graded exercise regimes (2).

I am not that familiar with the Norwegian health system but in other countries central schemes to collate information on adverse events associated with interventions, such as the yellow card scheme, are not available for nonpharmacological interventions (such as CBT and GET), increasing the importance of survey data.

While some efficacy has been reported for CBT and GET, the measures used have generally been self-reported. Objective results are less impressive. For example, a review of three Dutch CBT studies found that no increase in activity levels, as measured by motion sensors, was recorded (above those in the control groups) despite improvements being reported in fatigue, as well as other subjective measures in the individual studies.

The recently published PACE Trial got a lot of positive media coverage. However, on the only measure that could be described as being an objective measure, the six-minute walking distance (6MWD), there was no difference between the CBT and control groups. The GET group did improve on the 6MWD. However, 379m is not a particularly impressive result at 12 months considering 644m is the distance reference equations would estimate for this cohort.

Anyone familiar with such evidence could justifiably be cautious in statements about CBT and GET.

A common threshold for interventions to be seen as evidence-based is at least two positive (high quality) RCTs. Most posited therapies in the field have not been subjected to two RCTs. Any comments on other therapies, including on the Lightning Process, should certainly be tempered in the meantime.

References:

[1]. Bjorkum T, Wang CE, Waterloo K. [Patients' experience with treatment of chronic fatigue syndrome.] Tidsskr Nor Laegeforen. 2009 Jun 11;129(12):1214-6

[2]. Kindlon T. Reporting of Harms Associated with Graded Exercise Therapy and Cognitive Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Bulletin of the IACFS/ME. 2011;19(2):59-111. http://www.iacfsme.org/BULLETINFALL2011/Fall2011KindlonHarmsPaperABSTRACT/ tabid/501/Default.aspx

[3]. Chambers D, Bagnall AM, Hempel S, Forbes C. Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. J R Soc Med. 2006;99:506-20. Review.

[4]. Wiborg JF, Knoop H, Stulemeijer M, Prins JB, Bleijenberg G. How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity. Psychol Med. 2010 Aug;40(8):1281-7.

[5]. White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011;377:823-36.

Conflict of Interest: I am the Assistant Chairperson and Information Officer of the Irish ME/CFS Association. All my work for the Association is unpaid

On 2014 Sep 13, Vahid Rakhshan commented:

A detailed version of this review and the author's response can be found from this address (LINK).

Results

(1) In the methods, it was stated that ANOVA and Duncan post hoc test had been used to analyze the data. However, in the results, it was Tamhane post hoc test. These two completely differ.

(2) There was not even any mention of the name ANOVA or its P values.

(3) There were numerous pairwise comparisons in this study. However, most of them had not been reported and even many of comparisons that had been reported, lacked P values.

(4) Finally, it is stated that “For further elucidation of the reasons for ion release in the different solutions, the pH values of the 3 mouthwashes and distilled deionized water were measured.”… (A) The pH of mouthwashes should have been reported in the Methods section, not at the end of the Results. (B) A statistical test was needed for this purpose.

Discussion

(5) It is stated (p 732) that “all release is completed within 4 weeks”. The level of ion release reduces after sometime, but does not finish in the said period or even longer.^1,2

(6) This sentence (p 732) should have been stated very cautiously: “Chlorhexidine … caused not significantly higher release of copper than did Persica” A non-significant result is not of internal validity to be stated like something valuable.

(7) I could not understand the next sentence: “Since the pH values for mouthwashes had no significant difference in the acidity of the 3 mouthwashes, this could be attributed to the corrosiveness of chlorhexidine compared with the other 2 mouthwashes”… How did the authors find out that the pH values were not significantly different? This sentence was quite incorrect. Also the rest of the sentence was vague.

(8) I simply did not understand this sentence (after carefully reading the whole paper for some times): “We measured the means of ions released from every bracket in separate vials, but, on the basis of about 20 brackets in a patient’s mouth in clinical use, the results might become clinically significant.” What result might become significant? What are the authors talking about? There was no clue in the previous or later paragraphs.

Conclusion

Overall, conclusions were few and unsubstantiated. (9) The comparisons reported do not substantiate the first sentence of conclusions.

(10) The second sentence is not at all relevant to this study. It was not at all based on the findings or even the scope of this article.

Abstract

(11) Many of comparisons were done at a level of significance adjusted to 0.008. However, in the abstract “P < 0.05” or “P > 0.05” are introduced as indicators of statistical significance or lack of it.

References

1. Amini F, Rakhshan V, Mesgarzadeh N. Effects of long-term fixed orthodontic treatment on salivary nickel and chromium levels: a 1-year prospective cohort study. Biol Trace Elem Res 2012;150:15-20.

2. Amini F, Rakhshan V, Sadeghi P. Effect of fixed orthodontic therapy on urinary nickel levels: a long-term retrospective cohort study. Biol Trace Elem Res 2012;150:31-6.

On 2016 Aug 19, Lydia Maniatis commented:

Please find comments on PubPeer.

On 2014 Jan 08, Brett Snodgrass commented:

Dear Author,

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

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

I am moved by Dr. Lurie's pleas for the scientific community to produce accurate medical nomenclature, and I ask that others consider his please. http://www.ncbi.nlm.nih.gov/pubmed/18505600 http://www.ncbi.nlm.nih.gov/pubmed/22176755 http://www.ncbi.nlm.nih.gov/pubmed/22704295 http://www.ncbi.nlm.nih.gov/pubmed/23332812

In 2013, it is unfortunate to note that many peer-reviewed articles refer to arterial connections as "veins”. There are several reasons that referring to arteries as veins is potentially harmful.<br> For additional commentary, please see https://twitter.com/BrettSnodgrass1/status/417897291404812288

Comments or suggestions are welcome.

Thank you very much.

On 2016 Sep 06, Morten Oksvold commented:

Please note that part of this study is not reliable due to report of falsified/fabricated data in figure 3C:

"...Respondent falsified and/or fabricated the results in Figure 3C by using the same gel images to represent expression of PLDN in fibroblasts and melanocytes".

A full report has been published by ORI:

http://ori.hhs.gov/content/case-summary-cullinane-andrew-r

On 2014 Feb 14, David Keller commented:

In response to the editorial “Opioids for Chronic Pain”:

1) The authors distinguish between patients with chronic pain, and patients whose painful condition has a “clear end point of cure or death” (e.g. cancer). They propose restricting or denying opioid prescriptions for chronic pain patients. I disagree. If a patient with severe chronic pain might obtain some relief from opioid therapy, it is wrong to deny the patient that choice.

2) The authors argue that opioids only reduced pain scores by approximately 30% in clinical trials. Why not let the patient decide whether a 30% reduction in pain is worth the side effects and risks of opioid therapy? The degree of pain reduction is subjective and varies between individuals.

3) Overdose deaths caused by opioid abuse are tragic, and we need to work harder to prevent them. At the same time, we are obligated to relieve suffering, and if opioids are required, then they should be an option. Doctors need to educate patients on the safe use of opioids, as with other drugs which can cause overdose deaths (e.g. warfarin, insulin). If a patient requires escalating doses of opioids, or if their physician is uncomfortable about their treatment for any reason, they should be referred to a pain specialist.

4) The authors argue that government regulations make it too burdensome for physicians to prescribe strong opioids, which require monthly visits and non-refillable scripts. We should work to reform those regulations, not use them as an excuse to under-treat pain patients.

5) The authors advocate trying NSAID's, anti-depressants, and physical therapy before prescribing opioids. However, some patients are in too much pain to tolerate physical therapy. Depression caused by unrelenting physical pain may not remit until the pain is treated. And NSAID's can worsen hypertension, coronary disease, renal insufficiency, peptic ulcer disease and congestive heart failure. Opioids can often be prescribed safely in these conditions when NSAID's cannot. Adjunctive treatments should supplement opioids which are required for severe pain, with the goal of tapering the opioids as tolerated.

It is true that physicians need to exercise greater care when prescribing strong opioids, but to deny or restrict opioids for chronic pain patients is not humane or sensible.

To facilitate discussion, I respectfully request the person who found this comment "not helpful" to state their reason

On 2016 Nov 20, Morten Oksvold commented:

An investigation committee at Wayne State University (WSU) recommends that 42 articles from Fazlul Sarkar to be retracted (report finished August 31, 2015). This article represents one of them.

This information was published by Retraction Watch (November 17, 2016) and you can find a link to the full report here:

http://retractionwatch.com/2016/11/17/details-of-investigative-report-into-sarkar-released-by-aclu/

This article should therefore no longer be cited.

On 2013 Nov 04, Jamie Horder commented:

In keeping with these results, van Pelt et al van Pelt S, 2012 reported strong heritability of the peak frequency of visually-induced gamma band oscillations, in a MEG study of 80 healthy twins (20 DZ pairs and 20 MZ pairs).

On 2014 Dec 10, Kath Wright commented:

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

On 2013 Oct 29, Kenneth Witwer commented:

This paper describes an extremely well controlled study of the respiratory tract microbiome by high throughput sequencing. In addition to the interesting biological findings, the article (along with Charlson ES, 2012) has important technical implications. Nucleic acid contamination is widespread and will confound results if not controlled for carefully, as these authors have so elegantly done. Here, diverse sequences were obtained even from "microbiologically sterile" solutions and medical instruments. Users of sensitive sequencing techniques to investigate foreign sequences should take note.

On 2014 Jan 12, Brett Snodgrass commented:

Dear Authors,

Thank you very much for the excellent publication and acknowledging that the connections between the coronary arteries and left ventricle were not probably not veins.

These connections may represent the vessels of Wearn, which appear unusually prominent.

An applicable ICD9 code might be 746.85, coronary artery anomaly, as it may meet the clinical criteria for the definition of fistulae.

Referring to these arterial connections as Thebesian veins has caused me much confusion when I was trying to understand the simple relationship of pulmonary atresia with intact ventricular septum and the coronary arteriopathy seen in PAIVS. With the growth of social media, and electronic data storage, I think that we may now be able to address the diffuse distribution of ambiguous or misleading nomenclature that fills as least half of related publications.

Dr. Paul Lurie's plea for collaboration in this regard has motivated me to take several steps in an effort to try to help produce accurate, simple, precise anatomic nomenclature and include:

1. I collaborated with Elsevier to help get the article by Wearn et al. changed to open-access. http://bit.ly/JTWearn

2. I obtained the original article (through ArtRieve http://www.artrieve.com/) written by Thebesius and uploaded the first digital copy. http://bit.ly/Thebesius

3. I published or wrote in the American Journal of Cardiology, Cardiovascular Pathology, Twitter, Facebook, Google Plus, and directly E-mailed several authors that were publishing related content.

4. I have posted numerous PubMed Commons comments. I regret that they may not always be helpful to every user, but I echo Dr. Lurie’s plea for collaboration in this regard. The PubMed Commons commentary is a welcome means with significant potential to vastly improve the peer review process.

My aim is that researchers in the future will probably not need to read more than 30 articles before they realize that myocardial sinusoids indeed exist, they were defined by Wearn, and that Thebesian veins are not arteries.

Please see

1. http://bit.ly/JTWearn

2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1933738/

3. http://bit.ly/vasaThebesii

4. http://bit.ly/ThebesianByPratt

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

Comments and suggestions are welcome.

Thank you very much.

On 2013 Jul 01, Joshua L Cherry commented:

This paper argues that protein evolution proceeds in a particular way: changes to the protein surface occur, and these enable changes to the core. Such a process would be non-time-reversible: fixation of the back-mutation(s) of the core, followed by the thus enabled backward change in the surface, is precluded, or at least less likely. This would be odd long-term behavior in the presence of fixed selective constraints. Furthermore, it is not clear how such irreversibility could be detected by the methods employed. This interpretation of Fig. 4A requires either that our observations start at some special time in the evolutionary process, or that the long-term process is somehow different from the sum of its parts. This is particularly strange-seeming because the longer evolutionary distances correspond to greater distances backward in time from contemporary species to common ancestors.

The phenomenon in Fig. 4A is in fact expected as an artifact of saturation effects. Rapidly changing positions become subject to such effects at shorter overall distances than slowly changing positions. Because surface positions are on average more rapidly evolving than core positions, the form of the nonlinearities in Fig. 4A is expected even in the complete absence of surface-core interactions.

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT006895906. We believe the correct ID, which we have found by hand searching, is NCT00685906.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2016 Aug 17, Marco Galardini commented:

This software and server is no longer being actively maintained and supported (even though there might be occasional bugfixes and replies to simple requests). The recommended replacement is Medusa (http://combo.dbe.unifi.it/medusa and http://bioinformatics.oxfordjournals.org/content/31/15/2443)

On 2014 Aug 10, Matthew Katz commented:

CALGB 8433 proved the ability to improve cure rates in non-small cell lung cancer by combining chemotherapy with radiation. As of 2014, platinum-based regimens are still standard. The trend has been toward concurrent chemoradiation based on small increases in survival. But some patients still may benefit from a sequential approach to treatment.

On 2013 Oct 25, Gary Mirams commented:

I would like to draw attention to the fact that the results indicated in our paper for the Decker 2009 model in Figure 5 are inaccurate, due to a bug in the CellML representation of the model. There are details in a blog entry here.

This doesn't contradict any of the conclusions of the paper (we did suggest in one case that "This suggests the possibility that the CellML implementation of the model still requires curation"). Rather, this observation strengthens the idea that the community must do more rigorous curation of models. But I want to notify readers that the results shown for the Decker 2009 model are inaccurate.

On 2016 Feb 07, Fang-Cheng Yeh commented:

The tool and source code are available at http://dsi-studio.labsolver.org

On 2015 Jul 02, Anne Marie Cunningham commented:

There was some discussion of this paper here on my blog http://wishfulthinkinginmedicaleducation.blogspot.co.uk/2009/07/where-do-junior-doctors-look-things-up.html

On 2014 Feb 28, Valeria Fadda commented:

Valeria Fadda, Dario Maratea, Sabrina Trippoli, Roberta Gatto and Andrea Messori - HTA Unit, Regional Health System, 50100 Firenze (Italy)

Since the meta-analysis by Maratea and co-workers was carried out with relative risk (RR) as outcome measure, we recomputed these results according to the outcome measure of risk difference (RD) by using random-effect model. Figure 1 (available at http://www.osservatorioinnovazione.net/papers/thr_res2014.jpg), show the outcome measures (RD) calculated for individual trials (squares = outcome measure; horizontal bars = 95%CIs of the outcome measure) and for the pooled analysis (diamond in blue and vertical dotted line in red). I2 is a measure of heterogeneity. Statistical calculations were performed by the OMA software (Open Meta-Analyst version 4.16.12, Tufts University, U.S., url http://tuftscaes.org/open_meta/). The complete references for the 10 randomized trials can be found in the article Maratea D, Fadda V, Trippoli S, Messori A. Prevention of venous thromboembolism after major orthopedic surgery: indirect comparison of three new oral anticoagulants. J Thromb Haemost. 2011 Sep;9(9):1868-70.

Abbreviations: Ev, number of events; Trt, number of patients receiving treatment.

On 2014 Nov 23, Harri Hemila commented:

A manuscript version is available at handle

On 2015 Jul 21, Bill Cayley commented:

A great example of when Less is More: https://lessismoreebm.wordpress.com/2015/07/21/safety-and-sterilization-of-mosquito-net-mesh-for-humanitarian-inguinal-hernioplasty/

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT00624930. We believe the correct ID, which we have found by hand searching, is NCT00624390.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2015 May 22, University of Kansas School of Nursing Journal Club commented:

Team 1: Courtney Borchers, Elizabeth Bruns, Jesi James, Israel Mendoza, Elizabeth Murphy, Faith Nightingale, Kimberly Seals

Section 3 Journal Club: A review of Smith, C. A., Fisher, C., & Mercer, A. (2011) Rediscovering nursing: A study of overseas nurses working in Western Australia

Background Introduction:

The article by Smith, Fisher, and Mercer (2011) studied the work experience of internationally-educated migrant nurses with a non-English speaking background who came to practice in Western Australia (WA), Australia from various countries around the world.  This study was initiated in hopes to gain perspective from competent migrant nurses who must adjust their knowledge, skills, and attitudes about nursing to those of the host country for which they seek employment.  Our team chose this article because we have discussed the concept of migrant nurses in class; in addition, the movement to develop a more diverse nursing work force will impact our nursing careers as the United States becomes even more diversified in the years to come.  This article fills a knowledge gap by providing us with information about the importance of understanding the diversity in practice of internationally-educated migrant nurses and how to better facilitate the transition of the migrant nurse into the work environment.

Methods:

Our group utilized the CINAHL database to find this particular article. In this study, Smith, Fisher, and Mercer (2011) performed a qualitative study using transcendental phenomenology and Moustakas’ method of analysis for interpretation of results after conducting personal interviews. Open-ended questions about experiences and feelings were asked and responses were audio-taped and transcribed.

Recruitment in the form of posters and flyers were distributed in two hospitals and participants were ultimately recruited as a result of snowball sampling. Thirteen women from nine different countries who lived in WA between 4 and 20 years were selected for the sample. Countries of origin included China, South Africa, Japan, Taiwan, Zimbabwe, Hong Kong, the Philippines, Sweden, and Nepal. All nurses came from non-English speaking countries, had a non-English speaking background but were still linguistically competent, and were all qualified to work as nurses in Western Australia. Ethical approval was granted by the Human Research Ethics Committee of the University of Western Australia, participants were informed about the purpose of the study, and were promised anonymity and confidentiality.

Findings:

Key findings of this particular study by Smith, Fisher, and Mercer (2011) were summarized into four themes: preparedness to work, working with patients, working with doctors, and professionalism.  Regarding preparedness to work, it was concluded that although nurses were deemed competent, had gained registration to practice, and could identify the basic role of the nurse; they found many concepts of nursing in WA to be very different from nursing practice in their home country.  For example, some nurses felt that the scope of clinical skills were more limited and less advanced than the scope of practice in their home country.  However, nurses were puzzled that the broadened scope of practice in terms of emphasis on communication, holistic patient care, and the expectation to know about specialized services in WA was understood as a norm.  Regarding working with patients, nurses expressed that initially they were surprised at the decreased patient load compared to their home country, but eventually understood that the reasoning for this was to promote the holistic and patient-centered approach for which they were so astounded about previously.  In regards to working with doctors, some nurses expressed that the nurse-doctor relationship was more relaxed and less formal in WA, yet they still felt a strong hierarchy that did not exist in their home country.  When it came to professionalism, participants admitted that the working conditions and pay were more favorable in WA than in their home country and felt valued as nurses within the health care system, however, they felt a low level of respect in regards to nursing as a profession from patient’s and society in general.  The study group also felt a sense of lack of unity and motivation from native nurses in WA and contributed these themes to lack of professionalism enforced by the WA health system as a whole.  The results concerning the four themes discussed were consistent with the literature and findings from other studies conducted throughout the world. 

Limitations of the study were not discussed but should include a small sample size. 

Implications:

Similar to the US, migrant nurses who wish to work in Australia must pass certain eligibility criteria and may be required to take a competency test or pursue further education.  Migrant nurses in Australia must also pass the Occupational English Test or the International English Testing System (Smith, Fisher, & Mercer, 2011).  Regardless of the country in which an internationally-educated nurse wishes to work, all migrant nurses ultimately have to adjust their nursing practice to however the host countries contextual social, political, and economic constructs have made nursing as a profession to become.  According to Newton, Pillay, and Higginbottom (2012), “...Circumstances differ between countries to such an extent that there may be wide variation in the context of health care delivery and the education of health professionals, including nurses” (p. 535).  It is important to understand that the migrant nurse may feel many emotions as he/she may potentially learn about a very different set of nursing standards than his/her home country’s’ standards.

These particular types of studies are important to nursing and nursing practice because the findings demonstrate the need for awareness of nurses to aide in the integration and transition of internationally-educated migrant nurses into practice.  It is also important because educational efforts for cultural competency in the academic setting will continue to grow and become more necessary as the United States is continually becoming more diversified.  

In conclusion, our group feels this topic is important because we, as future nurses, will need to show compassion toward the migrant nurse’s concerns, as well as an eagerness to learn about what they already know.  We will also need to demonstrate a culture of unity and will ultimately need to assist migrant nurses as they go through the journey of becoming accustomed to the American nursing ways.

References

Newton, S., Pillay, J., & Higginbottom, G. (2012). The migration and transitioning experiences of internationally educated nurses: a global perspective. Journal Of Nursing Management, 20(4), 534-550. doi:10.1111/j.1365-2834.2011.01222.x

Smith, C. A., Fisher, C., & Mercer, A. (2011). Rediscovering nursing: A study of overseas nurses working in Western Australia. Nursing & Health Sciences, 13(3), 289-295. doi:10.1111/j.1442-2018.2011.00613.x

On 2016 Feb 14, Daniel Schwartz commented:

The Gupta Perioperative Cardiac Risk can be calculated online or via a mobile app here:

https://qxmd.com/calculate/gupta-perioperative-cardiac-risk

Conflict of interest: Medical Director, QxMD

On 2017 Mar 23, Misha Koksharov commented:

By the way, there was an older study on the same topic and with the same problems: Yamazaki S, 1994

On 2015 Jun 23, Anne Niknejad commented:

citation:'Prpsap2 negatively regulates phosphoribosyl pyrophosphate (PRPP) synthetase [22].'

Checking ref.22 (http://www.ncbi.nlm.nih.gov/pubmed/?term=9545573), there is this sentence: 'The contribution of PAP41 to the regulation of PRPP synthesis remains to be studied.'

PAP41 is short name for Prpsap2 (http://www.uniprot.org/uniprot/O60256)

On 2013 Dec 22, Lothar Hennighausen commented:

MiR-193b and miR-365-1 are not required for the development and function of brown fat in the mouse (PMID: 24356587)

On 2017 Aug 06, Fernando Castro-Chavez commented:

Dear Reader, Among other things, in this article I present the perfect mathematical symmetry and balance between the opposite quadrants of the classic circular rotating genetic code; and also, the rules of variation are expanded by comparing each compatible organism as an orbit with each dot within such orbit being a variety of it, such as those more than 200 breeds of dogs, being also genetically compatible with them the savage wolves and coyotes and jackals and dingoes, and New Guinea´s singing dogs; the same with the South American Camelids, being genetically compatible the Llama, the Guanaco, the Alpaca and the Vicuña; the same for all the varieties of finches from the Galapagos Islands, just to put some examples of compatible organisms that have been systematically misclassified as if they were many times even members of different genus, not to say "species", this rampant classifying mistake of organisms in biology is as dramatic and drastic as if the different colors of humans had been the basis to misclassify them as different "species", which fortunately did not happen with humans, but it did happen with other every organism, starting with the dog, the "best friend of man", sincerely, Fernando Castro-Chavez.

On 2013 Oct 27, Gary Mirams commented:

None

On 2013 Oct 27, Gary Mirams commented:

The MICEE database is now available for testing https://www.micee.org/. Please try to enter details for any cardiac electrophysiology experimental papers, and give feedback on usability and usefulness, together with any changes you would propose to the schema.

On 2014 Dec 17, Sean Ekins commented:

Find out about CDD Vault here https://www.collaborativedrug.com/

On 2016 Aug 21, Morten Oksvold commented:

Please note that this article represents one of eleven publications which were found to contain false data, after an investigation led by ORI in 2015:

https://ori.hhs.gov/content/case-summary-dasmahapatra-girija

This article should therefor not be cited.

On 2013 Jun 26, Matthew Stephens commented:

This paper is a beautiful example of a simple idea leading to useful inference (and a type of inference that is generally really difficult). I have to admit I would never have tried this myself, anticipating that variation in mutation rate across the genome would have caused too many problems, but it seems that this is less of a concern than I would have expected.

On 2014 Nov 30, Morten Oksvold commented:

The mice shown in suppl. fig 9 have ulcerating tumors and some of the mice have tumors more than 6cm3 in size. How was the animal experiments in this study reviewed and approved by the MGH Subcommittee on Research Animal Care? Why are the Editors at Nature and its reviewers apparently unaware of the generally accepted guidelines for animal welfare?

On 2015 Sep 04, David Vaux commented:

None

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/286/35/31022.full.pdf?sid=a8d5dc2c-dd64-4b19-bf5e-c46f7deb9f49

"This article has been withdrawn by the authors. The gJNK panel from SK-OV-3 cells was reused in the gJNK panel from OVCAR-3 cells in Fig. 1A. The tubulin panel in Fig. 2 C was reused as the right g-p38  in Fig. 4 B, and as the IP: gMLK3 and IB: gMLK3 panel in Fig. 6F. The left p473 AKT immunoblot and the right p308 AKT immunoblot in Fig. 4D were inappropriately manipulated. Also, the right AKT immunoblot from Fig. 4D was reused as the right AKT immunoblot in supplemental Fig. S2 B. Lanes 2 and 3 of the JNK immunoblot in Fig. 6D were reused in the JNK immunoblot from Fig. 6 E. The MKK4 immunoblots in Fig. 7A were duplicated. Lanes 2 and 3 and lanes 5 and 6 of the upper JNK immunoblot in Fig. 7C were reused in the lower left and right JNK immunoblots, respectively. The AKT immunoblot from SVOG-40 cells in supplemental Fig. S2A was reused in the AKT immunoblot from SVOG-40 cells in supplemental Fig. S2B. The pc-Src panel from supplemental Fig. S3A and the right AKT immunoblot from supplemental Fig. S3C were manipulated inappropriately. The authors state that these errors do not affect the results or conclusions of the work."

On 2017 Aug 07, Randi Pechacek commented:

Jonathan Eisen wrote a blog post on microBEnet using this paper as inspiration for a discussion on the microbes in tobacco products.

On 2013 Jun 22, Martin Fenner commented:

This paper is discussed in a comment to Longo DL, 2013.

On 2014 Jan 20, Ellen M Goudsmit commented:

There are other criteria for ME based on the work of experts such as Drs. Ramsay, Dowsett and Parish. Lack of interest in classic ME has made it extremely difficult to place these criteria in the scientific domain.

Myalgic Encephalomyelitis (ME). Criteria and clinical guidelines 2014.

Sandra Howes<br> Ellen M Goudsmit PhD FBPsS<br> Charles Shepherd MBBSc

Abstract

Myalgic encephalomyelitis (ME) is a disabling condition characterised by profound fatigue following minimal exertion and a delay in recovery after exertion ends. In 1988, when specialists introduced the concept of chronic fatigue syndrome (CFS), it was assumed that the illness in question was identical to ME but the lack of consensus criteria for the latter has prevented the testing of this assumption. In this article, we propose criteria and guidelines which can be used to study ME and determine whether it is a synonym for CFS or one of several subgroups contained within the CFS construct. If clinically meaningful differences are identified, the criteria may help to increase diagnostic precision and facilitate further research into the cause, course and treatment of ME.

Extract

The criteria for research into ME [1]

All patients should fulfil the following five criteria: 1. A new onset of significantly abnormal levels of muscle fatiguability and/or muscle weakness, precipitated by relatively minor levels of activity. Symptoms typically worsen during the next 24-48 hours. 2. The presence of symptoms indicating the involvement of the brain and central nervous system (e.g. impaired short-term memory and concentration, disturbed sleep patterns, balance problems). 3. Periods of impaired circulation compatible with autonomic dysfunction (e.g. facial pallor, disturbances in thermoregulation including inappropriate sweating and sensitivity to both heat and cold; postural hypotension and/or orthostatic intolerance). 4. Fluctuation of symptoms, from hour to hour and day to day. 5. These symptoms must have been present during the past three months (to exclude patients with the debility which often follows illnesses such as influenza).

Guidelines

Many symptoms experienced by people with ME are also reported by people with other disorders. The most prevalent of these include pain – which can be muscular, arthritic or neuropathic in character; hyperacusis and tinnitus; photophobia and blurred vision; frequency of micturition and hypersensitivity to chemicals and drugs. Also common are symptoms suggestive of immune system dysfunction and/or persisting infection, such as episodes of low-grade fever (not exceeding an oral temperature of 38.6C) combined with feeling feverish; sore throat which may be persistent or recurrent, and arthralgia.

While the presence of these symptoms are not discriminative, the marked diurnal fluctuations in severity are typical of ME. Exacerbations are frequently triggered by physical or mental exertion and this association should always be sought whilst taking the history.[2] Characteristic physical signs are sometimes seen in ME and in combination with the symptoms above also contribute to the validity of the diagnosis. Nevertheless their absence does not exclude the condition. They are as follows: 1. Pharyngitis. 2. Tenderness and possible enlargement of lymph nodes. 3. A positive Romberg test or Fukuda test.

Course

Although ME often follows an infection, usually a viral illness (which may be sub-clinical), it may also be triggered by other factors such as immunizations, trauma and exposure to chemicals. Furthermore, in a minority of patients, ME has a gradual onset with no apparent triggering factor. For these reasons, and in line with the criteria for CFS, evidence of a preceding viral illness is not a prerequisite for diagnosis or inclusion in a study group.

Assessment, investigation and diagnosis

Because it is vital that the samples used in research are as 'pure' as possible, the presence of certain co-morbid disorders would be grounds for disqualification. Some of the more common alternative diagnoses to be borne in mind before selecting a participant for a study on ME are listed in Shepherd and Chaudhuri[2,p.15]

Other reasons for exclusion from research into ME

It is of particular importance to identify cases of chronic fatigue which can be largely explained by psychological factors. For example, if there are signs of persistent anhedonia, apathy, low self-esteem, feelings of worthlessness and guilt, the possibility of primary depressive illness should be considered and, if there is any doubt, the participant should be excluded from the study. Similarly, if the patient has had any other illness or undertaken any treatments - orthodox, complementary or nutritional - in the previous three months, their inclusion may introduce additional variables which could confound the results.

Measures to aid diagnosis and selection of samples

We recommend that the Profile of Fatigue-Related Symptoms (PFRS) developed by Ray et al. [3] may help support the diagnosis and suggest that a person should score at least 2 out of six on the two items relating to the presence of muscle weakness. This is a core symptom and the score provides additional evidence of its presence and severity. The testing of muscle fatigue on two occasions, at least 24 hours apart, may also be of value.

A protocol was developed by Dr Parish, a rheumatologist who has studied ME since 1955. Using criteria almost identical to those proposed above (Wood, personal communication), Paul et al. [4] found a significant decline in quadriceps strength which persisted after 24 hours in all the participants. Moreover, there were significant differences between the patients and controls during the recovery phase, 200 minutes following exercise, when the results of the latter had returned to normal, and after 24 hours. This protocol is different to others that have evaluated post-exertional fatigue in that it demands a continually increasing energy cost throughout the duration of the exercise period, and therefore differs from the steady levels achieved in cycle ergometry used in other studies.<br> However, one cycling exercise test that deserves further consideration was recently described by Snell et al.[5] Although the patients were diagnosed with CFS, all reported a worsening of symptoms after physical activity. Various tests using a cycle ergometer were conducted to evaluate work efficiency, i.e., oxygen consumption and work output at the ventilatory/anaerobic threshold. The results revealed lower workloads and oxygen consumption at peak exercise compared to sedentary controls but none of the individual tests helped to discriminate between the groups on day 1. However, data from the second session showed a decrease in performance in patients that was not seen in controls and identified two measures which contributed most to the discrimination between the groups (workload at ventilatory threshold and peak workload). The researchers noted that their findings may have been affected by the heterogeneity of the sample but the results helped to correctly classify over 95% of the participants and demonstrated the importance of a second test.

[1] Goudsmit E et al. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychol Update. 2009;18(1):26-33.

[2] Shepherd C, Chaudhuri A. ME/CFS/PVFS. An exploration of the key clinical issues. 4th ed. ME Association; 2008.

[3]Ray C et al. Development of a measure of symptoms in chronic fatigue syndrome: The profile of fatigue-related symptoms (PFRS). Psychol Health. 1992;7:27-43.

[4] Paul L et al. Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. Eur J Neurol. 1999;6:63-69.

[5] Snell CR et al. Discriminative validity of metabolic and workload measurements to identify individuals with chronic fatigue syndrome. Phys Ther. 2013;93(11):1484-1492.

On 2014 Jan 21, Ellen M Goudsmit commented:

The International Consensus Criteria or ICC initially appeared to be resolve a lot of problems relating to heterogeneity of the population, describing many of the symptoms of classic ME and avoiding the vagueness of the term ‘malaise’ used in case definitions for CFS. The ICC are more specific, referring to a pathological inability to produce sufficient energy on demand, “postexertional symptom exacerbation”, “postexertional exhaustion” , “a marked, rapid physical and/or cognitive fatigability in response to exertion”, a prolonged recovery period and “a low threshold of physical and mental fatigability (lack of stamina) resulting in a substantial reduction in pre-illness activity level”. Postexertional neuro-immune exhaustion (PENE) as they named this characteristic feature, had to cause marked disability and was compulsory for diagnosis. However, it's not easy to assess in practice. In a recent study by Jason et al. [1], more than 10% of the patients selected using the ICC did not report that minimal exercise made them tired. This is possibly because the researchers required only one of the characteristics of PENE to be present, rather than all.

A second study from Jason and his colleagues also compared the CDC criteria with the ICC and showed that while the latter identified a subset of patients with more functional impairments and physical, mental and cognitive problems, they also had a higher rate of psychiatric illness.[2] Indeed, 61.5% had a current psychiatric diagnosis compared to 27% who fulfilled the CDC criteria. Again, this may be a result of patients reporting evidence of post-exertional worsening but not meeting every characteristic of PENE. This 'short-cut', also likely to occur in clinical practice, might have led to misclassification.

For example, another interesting finding was that more than a half had a gradual onset. This plus the higher rate of psychiatric illness are at odds with descriptions of individuals with classic ME, more of whom report an acute infectious onset and symptoms such as muscle weakness and an intolerance to alcohol.[3 p.147, 4,5] They also tend to have lower rates of psychiatric illness.[6,7,8] According to Jason et al. [1], the requirement of a larger number of symptoms (at least eight for the ICC versus five for the CDC criteria) might “inadvertently increase the rate of psychiatric morbidity” and they recommended further refinement of case definitions focusing on a small set of core symptoms. Finally, based on a review of all criteria, they noted some of the disadvantages of polythetic case definitions that include patients on the basis that they experience a certain number of listed symptoms, many of which are ubiquitous and do not allow clinicians to differentiate between CFS and other disorders.[1,8,9]

[1] Jason LA, Sunnquist M, Brown A, Evans M, Vernon, SD, Furst JD, Simonis, V. Examining case definition criteria for chronic fatigue syndrome and myalgic encephalomyelitis. Fatigue: Biomed Health Behav. Epub 2013 Dec 11. Available from: http://dx.doi.org/10.1080/21641846.2013.862993

[2] Brown AA, Jason LA, Evans MA, Brown M, Flores S. Contrasting case definitions: The ME international consensus criteria vs. the Fukuda et al. CFS criteria. North Am J Psychol. 2013;15(1):103–120.

[3] Shepherd C. Living with M.E. 2nd ed. London: Cedar; 1992.

[4] Dowsett EG, Ramsay AM, McCartney RA, Bell EJ. Myalgic encephalomyelitis a persistent enteroviral infection? Postgrad Med J, 1990;66:526 530.

[5] Smith DG. Understanding M.E. The phenomenon of myalgic encephalomyelitis and acute onset post viral fatigue syndrome. London: Robinson Publishing; 1989. p. 184-185.

[6] Dowsett EG, Welsby PD. Conversation Piece. Postgrad Med J. 1992; 68:63-65.

[7] Yeomans JDI, Conway SP. Biopsychosocial aspects of chronic fatigue syndrome (myalgic encephalomyelitis). J Infect. 1991;23:263-269.

[8] King C, Jason LA. Improving the diagnostic criteria and procedures for chronic fatigue syndrome. Biol Psychol. 2005;68: 87-106.

[9] Goudsmit E, Shepherd C, Dancey CP, Howes S. ME: Chronic fatigue syndrome or a distinct clinical entity? Health Psychol Update. 2009;18(1):26-33.

On 2014 Oct 10, Ellen M Goudsmit commented:

Case definitions should also recognise the progressive form of the disease.

Howes and Goudsmit (submitted) suggest that :

A diagnosis of progressive ME is supported by the following:

1. Sudden increase in sensitivities and gastro-intestinal symptoms.
2. Sudden worsening of existing neurological symptoms or new symptoms, e.g. blurred vision in one eye, weakness in one leg, incontinence.<br>
3. Improvements are limited, disability tends to show a downwards trend.
4. Patient has to spend more time at home or in bed.
5. New auto-immune diseases e.g. symptoms consistent with Sjogren’s syndrome.

Supportive evidence of pathology:

MRI, abnormal white matter lesions not indicative of MS.

On 2014 Sep 22, Thomas Perls, MD, MPH commented:

The corrected version of this work is at: http://www.ncbi.nlm.nih.gov/pubmed/22279548

PLoS One. 2012;7(1):e29848. doi: 10.1371/journal.pone.0029848. Epub 2012 Jan 18. Genetic signatures of exceptional longevity in humans. Sebastiani P1, Solovieff N, Dewan AT, Walsh KM, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, Hoh J, Perls TT.

On 2014 May 21, Amanda Capes-Davis commented:

Please be aware that FL is not an amnion cell line. It is known to be cross-contaminated with HeLa, a cervical carcinoma cell line. For a list of known cross-contaminated or misidentified cell lines, see http://iclac.org/databases/cross-contaminations/.

On 2015 Dec 30, Vatsalya Vatsalya commented:

NIAAA 2012 overview (Pg. 47 of 304); web-link: http://pubs.niaaa.nih.gov/dicbr/NIAAA_DICBR_Overview_2011_2012_Final_01_19_2013.pdf

On 2017 Aug 17, Jesper M Kivelä commented:

This re-analysis He FJ, 2011 of an earlier version Cochrane review Taylor RS, 2011 considering cardiovascular events (CVD) at longest follow-up is based on wrong numbers extracted from trials (namely TOHP 1 trial). There were 17 CVD of total 231 (not 321) patients in intervention group and 32 CVD of total 311 patients in control group in TOHP I (Table 2) Cook NR, 2007. See also my comment in current version of Cochrane review Adler AJ, 2014. Contrary, different numbers were extracted by O´Donnell et al O'Donnell MJ, 2013 in their analysis of the same set of 4 studies than used in He FJ, 2011.

In current version of Cochrane review, average risk ratio was 0.81 (95% CI 0.66 to 0.98) for CVD at longest follow-up based on 6 studies (Analysis 1.5) Adler AJ, 2014. However, between-study variance was estimated to be zero which is implausible based on empirical evidence from Cochrane Database of Systematic Reviews Turner RM, 2012, Turner RM, 2015. In other words, a small amount of between-study variance should be expected even for end-points like all-cause mortality Turner RM, 2012, Turner RM, 2015.

On 2014 Dec 10, Kath Wright commented:

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

On 2017 Mar 01, Jörg Hakenberg commented:

GNAT results for Medline citations are now available from our Sourceforge project for download. Please see https://sourceforge.net/projects/gnat/files/results/medline/ .

On 2016 Feb 18, Kristina Hanspers commented:

The pathway in figure 10 is available in the "Open Access Publication" collection at WikiPathways: http://www.wikipathways.org/index.php/Pathway:WP2638. This pathway can be downloaded for use in network analysis tools such as Cytoscape and PathVisio.

On 2014 Apr 11, Alexis Verger commented:

This article has been retracted : http://www.cell.com/abstract/S0092-8674(11)00764-1

On 2014 Apr 11, Ivan Oransky commented:

A look back at press releases and media coverage of this now-retracted study when it first came out: http://retractionwatch.com/2014/04/11/fraud-fells-alzheimers-made-to-order-neurons-paper-in-cell/

On 2014 Apr 10, Ivan Oransky commented:

This paper has been retracted: http://retractionwatch.com/2014/04/10/retraction-four-appears-for-dirk-smeesters/

On 2014 Sep 25, William Cawthorn commented:

"impact factors remain the key measure of a journal’s prestige and, by inference, your own."

I've no doubt that impact factors are important to a journal's editors. But the idea that impact factors in any way reflect the quality or reliability of the science, or indeed the ability and creativity of an individual scientist, is very damaging.

http://www.sciencedirect.com/science/article/pii/S0960982207015163

On 2014 Dec 10, Kath Wright commented:

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

On 2014 Feb 27, George W Hinkal commented:

The National Cancer Institute has been investing in the development of an online webportal of curated cancer nanotechnology data called caNanoLab. The numerical data, nanomaterial characterizations and composition information for the eleven nanoparticles related to this publication have been added to the database and can be found at:

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=32669696&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=32669697&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=32669698&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=32669699&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=32669700&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=32669701&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=32669702&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=32669703&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=32669704&page=0&tab=ALL

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On 2014 Mar 12, George W Hinkal commented:

None

On 2013 Dec 10, Lorene M Nelson commented:

From the senior author of the original article: Please note that a reply to this letter by Hill-Burns et al. was published in the European Journal of Neurology; however, PubMed failed to index the reply letter. For those who are interested, here is the citation for the reply letter: Popat RA et al., Eur J Neurol 2011;18:e109.

On 2017 Aug 01, ANTHONY BAUGHN commented:

Anti-tubercular Activity of Pyrazinamide is Independent of trans-Translation and RpsA. Dillon NA, Peterson ND, Feaga HA, Keiler KC, Baughn AD. Sci Rep. 2017 Jul 21;7(1):6135. doi: 10.1038/s41598-017-06415-5. Dillon NA, 2017

https://www.nature.com/articles/s41598-017-06415-5

On 2013 Nov 15, Nikolaos Kokras commented:

Relates to Kokras N, 2012

On 2015 Sep 17, Tom Kindlon commented:

This study uses the (so-called) empiric CFS criteria (Reeves et al., 2005)

Although they don't make it very clear, this study used the Reeves et al. (2005) criteria(1) for defining Chronic Fatigue Syndrome (CFS) (sometimes described by the CDC as an operationalization of the Fukuda et al. (1994) criteria (2)). This can be seen by examining the Reeves et al. (2005) paper which shows that 43 people from the two-day study satisfied the Reeves et al. (2005) operationalization of the criteria which the number satisfying how they operationalized the Fukuda et al. criteria was considering less(1,2).

These (Reeves) criteria greatly increased the prevalence of CFS. The "empirical" definition gives a prevalence rate of 2.54% of the adult population(3) compared to 0.235% (95% confidence interval, 0.142%-0.327%) and 0.422% (95% confidence interval, 0.29%-0.56%) when the Fukuda definition was used in previous population studies in the US(4,5).

The definition lacks specificity. For example, one research study(6) found that 38% of those with a diagnosis of a Major Depressive Disorder were misclassified as having CFS using the empirical/Reeves definition. A letter of mine discussed my concerns in more detail(7).

Due to the problems with the criteria, these criteria have not been used by researchers outside those contracted to analyse CDC data (apart from Leonard Jason's research team who studied it and showed problems with it (6)).

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 Med. 2005;3:19.

2 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.

3 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.

4 Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC: Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Int Med 2003, 163:1530-1536.

5 Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S. A community-based study of chronic fatigue syndrome. Arch Intern Med. 1999 Oct 11;159(18):2129-37.

6 Jason, LA, Najar N, Porter N, Reh C. Evaluating the Centers for Disease Control's empirical chronic fatigue syndrome case definition. Journal of Disability Policy Studies 2008, doi:10.1177/1044207308325995.

7 Kindlon T. Criteria used to define chronic fatigue syndrome questioned. Psychosom Med. 2010 Jun;72(5):506-7

On 2016 May 03, Gregory Stupp commented:

It seems the authors have referred to the wrong GEO data set (GDS2642: colonoscopic biopsies from CD or UC patients), when the data in fact looks to have come from GDS1615: peripheral blood mononuclear cells from CD or UC patients).

As an example. The gene with the highest fold change in Table S1 is SERPINB2. This fold change can be seen in the GEO profile graph for GDS1615: http://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS1615:204614_at but not from GDS2642: http://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS2642:37185_at

I verified the rest of the genes using the data from the SOFT files and also using geo2r: https://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE3365 https://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE6731

On 2013 Jun 17, Jessie Tenenbaum commented:

With the disclaimer that this came out of my PhD lab (4 years after I left), I really like this paper. I remember seeing a naysayer comment (on GenomeWeb maybe?) questioning whether this belonged in STM, but this is exactly what big data mining approaches is meant to do- yes, it's about hypothesis generation, but if those hypotheses can then be validated in a model system, trimming years off the drug discovery process, that is truly impactful.

On 2017 Jan 20, Andy Collings commented:

A subset of experimental results from this study were the focus of a replication attempt as part of the Reproducibility Project: Cancer Biology (https://osf.io/e81xl/wiki/home/). The experimental designs and protocols were reviewed and approved in a Registered Report (http://dx.doi.org/10.7554/eLife.06847) and the results of the experiments were published in a Replication Study (http://dx.doi.org/10.7554/eLife.17044).