On 2015 Sep 10, Lydia Maniatis commented:

The authors claim that their data “characterize the luminance-to-lightness mapping in high-dynamic-range images that lack cues indicating the presence of multiple regions of illumination.” The assumption is that their checkerboards do not produce differential illumination or transparency effects, but a look at their stimuli proves otherwise. That checkerboards can produce impressions of differential illumination is acknowledged by Allred, Radonjic, Gilchrist & Brainard (2012) albeit non-commitally. The stimuli may lack known cues, but self-evidently they do not lack cues.

The authors conclusions are also complicated by the fact that in higher-range stimuli, the highest luminance was reported as glowing “on most trials.” They dismiss these results as being due to the presentation of stimuli on an “emissive display” but this doesn't explain why glow wasn't reported in the lower-range stimuli for targets of the same luminance.

On 2014 Mar 17, Gaetano Santulli commented:

Mega et al. report that in patients across the spectrum of acute coronary syndrome (ACS) low doses of the oral anticoagulant rivaroxaban reduced the risk of death from cardiovascular causes, myocardial infarction or stroke (1). Unfortunately, a large percentage of the enrolled patients was not at high cardiovascular risk. Thus, these results may be not applicable to subjects with an ACS who are commonly treated in routine practice (2). Moreover, patients with atrial fibrillation (AF), which represent up to 22% of subjects with ACS(3), were excluded from the study. Of interest, the Authors report that more than 1% of patients experienced AF, as ‘adverse event’, after rivaroxaban or placebo treatment. Although this is a small number of subjects, it would be of interest to see the data for this group presented separately. Indeed, this population represent the best category that may benefit from combined antiplatelet and anticoagulant therapy and these data could be noteworthy especially after the recent caveats stated by the Food and Drug Administration concerning this issue (4).

Disclosures: None.

References 1. Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in Patients with a Recent Acute Coronary Syndrome. N Engl J Med 2011. 2. Roe MT, Messenger JC, Weintraub WS, et al. Treatments, trends, and outcomes of acute myocardial infarction and percutaneous coronary intervention. J Am Coll Cardiol 2010;56:254-63. 3. Jabre P, Roger VL, Murad MH, et al. Mortality associated with atrial fibrillation in patients with myocardial infarction: a systematic review and meta-analysis. Circulation 2011;123:1587-93. 4. Mitka M. FDA advisory decision highlights some problems inherent in pragmatic trials. JAMA 2011;306:1851-2.

Gaetano Santulli, MD, PhD Columbia University gs2620@columbia.edu

On 2013 Oct 11, Hilda Bastian commented:

This review could not take into account lifestyle factors that often accompany healthier diets and lower risk of cancer, such as not smoking. Studies like those analyzed here probably aren't enough to establish that a nutrient can prevent disease: Moorthy D, 2013. In the case of fiber and colorectal cancer, a systematic review of randomized trials (Asano T, 2002) did not find a reduction of colorectal cancer either from fiber supplements or dietary intake as in, for example, the large National Cancer Institute trial: Schatzkin A, 2000. This trial evidence is not discussed in this review by Aune and colleagues. Anyone interested in this subject would be better off starting with the systematic review of trials and trials on fiber and resistant starch published since then: Ishikawa H, 2005, Burn J, 2011. Further discussion here.

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 NCT0139171. We believe the correct ID, which we have found by hand searching, is NCT01393171.

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 Mar 20, Anders von Heijne commented:

Reviewing the MR images in this case report there is clearly an older lesion in the right medial temporal lobe with atrophy. This is not commented on by the authors. One might speculate that the patient has had an earlier episode of HSE. Additional information would be valuable.

On 2013 Nov 01, Gerard Ridgway commented:

There is new version of this work (somewhat confusingly with an unchanged abstract) "Updated April, 18, 2013", Weiner MW, 2013

On 2013 Oct 23, M Mangan commented:

Actually I found out about this new NCBI commenting system from BioStar. And I wanted to give it a try.

Here's the discussion at Biostar: http://www.biostars.org/p/84222/.

It will be interesting to see if this is much different than forum-style discussions and other sites with comments. I like the idea of a place that's not unique to one publisher. But I expect it could be difficult to build community in the same way forums and blogs do, and manage the comments.

On 2013 Jul 09, Joshua L Cherry commented:

This work develops metabolic models for six E. coli strains, performs relevant experiments with these strains, and compares model predictions to observations. The authors state that they have demonstrated that "quantitative models of different strains of E. coli can accurately predict strain-specific phenotypes." The results, however, do not support this conclusion. In fact, they point to the opposite conclusion: the models had little or no value for predicting differences between strains.

The authors predicted and experimentally determined the abilities of the strains to use various carbon sources under aerobic and anaerobic conditions. Most individual predictions agree with observations, but this fact alone means little; all strains were able to utilize the vast majority of substrates, so that simply "predicting" all positives would yield 95% agreement. For the data in Table 5, results are statistically significant under aerobic conditions for only one strain (Fisher's exact test). Under anaerobic conditions the predictions fare better: 5 of 6 cases are statistically significant. However, none of this tells us whether the predictions capture differences between strains. To address this question requires more information than counts of the sort found in Table 5.

Additional file 7 of the article provides the necessary kind of data: predicted and observed utilization capabilities for individual substrates. For reasons not clear to me, it contains predictions for only 68 substrates, rather than the 76 reported in Table 5. I have searched this data for correct predictions of differences between strains. These would be cases where one strain utilizes a substrate, another fails to do so under the same conditions, and this is correctly predicted. Across all 68 substrates and all pairings of the 6 strains, there is just one such case. This involves aerobic utilization of phenylethylamine. Even this cannot be considered a success because predictions for the other four strains are all incorrect, and all four possible combinations of predictions and observations occur. All the other differences between strains are missed, and there are several predicted differences that are shown to be false by experiment.

The authors also predict and measure growth rate and yield for growth on glucose (actually, the flux balance analysis itself predicts only yield; conversion to rate relies on measured rates of glucose uptake). When the aerobic and anaerobic data are combined, correlations between prediction and experiment are strong and significant. However, these high correlations have nothing to do with differences between strains. Rather, they reflect the difference between aerobic growth and anaerobic growth. Simply assuming that the growth rate (or yield) is higher under aerobic conditions than anaerobic conditions, and that there are no strain differences, results in similar high correlations. So does randomly permuting the predictions among strains. As the authors note, correlations disappear when strains are considered under a single condition, so there is no evidence for correct prediction of differences among strains.

Thus, it appears that the predictions contain little or no information about phenotypic differences between strains. Reconciling the models and experimental results may aid our understanding of metabolism and help improve future predictions.

On 2014 Jan 08, Tom Kindlon commented:

The SF-36 subscale scores in this paper are norm-based scores

The SF-36 subscale scores in this paper are norm-based scores. This was confirmed by the authors following a question by me on the PLoS one site: http://www.plosone.org/annotation/listThread.action?root=21433.

On 2015 Aug 08, Karl Broman commented:

The paper describing the JavaScript library D3.js, which has had an enormous impact toward popularizing web-based interactive data visualizations, because it's totally awesome.

On 2013 Jul 05, Richard Simon commented:

This is an interesting and important paper but some have misinterpreted it’s findings. The authors addressed the prognostic significance of published gene expression signatures for breast cancer (mostly for non-metastatic disease). They demonstrated that prognostic signatures can be developed over 90% of the time from random sets of >100 genes and that the signatures generated from sets of random genes are often as prognostic as published gene expression signatures. The reason is that there are an enormous number of genes that are correlated with cell proliferation and cell proliferation is strongly correlated with prognosis (estrogen receptor expression is strongly associated with outcome and prognosis and there are thousands of estrogen receptor target genes). Most published gene expression signatures are no longer prognostic after adjustment for the proliferation meta-gene. The take home message is that authors of biological mechanism papers should not claim that the genes they discovered in an experimental model system have relevance for the human breast cancer by showing that a signature based on their genes are prognostic in human breast cancer. That claim is common in cancer biology. The paper should not be misinterpreted to mean that claims of the prognostic accuracy of gene expression signatures are erroneous or that such signatures are not potentially useful for medical decision making. In fact, there are well documented pitfalls in the evaluation of predictive accuracy of prognostic signatures (e.g. using the same dataset to develop the signature and to evaluate it without using complete cross-validation). Predictive signatures which identify patients most likely to benefit from a specific treatment tend to be more useful than prognostic signatures derived based on a heterogeneous collection of cases. Nevertheless, prognostic signatures can be therapeutically relevant. This paper is well done however and it’s conclusions are carefully drawn.

On 2014 Nov 17, Raphael Levy commented:

The existence and cell penetrating properties of "striped" nanoparticles have been challenged by Cesbron Y, 2012.

A detailed analysis of this body of work is published today in PloS One by Stirling et al; from the abstract: “through a combination of an exhaustive re-analysis of the original data with new experimental measurements of a simple control sample comprising entirely unfunctionalised particles, we conclusively show that all of the STM evidence for striped nanoparticles published to date can instead be explained by a combination of well-known instrumental artefacts, strong observer bias, and/or improper data acquisition/analysis protocols.”

On 2014 Nov 28, Juergen Borlak commented:

There has already been an extensive communication on this matter (see comments on the original manuscript in PLOS One at http://www.plosone.org/annotation/listThread.action?root=69409). Unfortunately, we note serious misconceptions that require clarification.

First, in our previous communications we already alluded to the methodology employed. Thus, all relevant information can be retrieved from the original paper. Furthermore, in our original study we alerted to the issue of underreporting and the difficulties in defining accurate incidences of ADRs. Apart from statistical issues, e.g. to determine an incidence of just 1 per 10,000 in the control group one would require 180,000 participants in the verum group, prospective studies are inevitably confounded by the study protocol inclusion and exclusion criteria that lead to additional bias. Second, in 2013 the pharmacovigilance risk assessment committee (PRAC) of the European Medical Agency (EMA) evaluated independently the evidence of flupirtine induced liver injury and concluded that the benefit still outweighs the risk for hepatotoxicity particularly when the treatment of acute pain with other analgesics (e.g. non-steroidal anti-inflammatory drugs, weak opioids) is contraindicated and the treatment duration is restricted to 14 days (http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Flupirtine-containing_medicines/Recommendation_provided_by_Pharmacovigilance_Risk_Assessment_Committee/WC500146103.pdf). In our previous communication we referred to the deliberations of the PRAC, however, based on the comment provided we must assume that the commentator has no confidence in the capabilities of the PRAC and this would also imply that the EMA apparently is unaware of the issue of ADR underreporting which is a somewhat baffling assumption. Lastly, we do not believe that an estimate of incidences of ADR without causality assessment adds to the science of drug safety. Indeed, an incidence of less than 1 in 10,000 may be found acceptable; however, for an individual suffering from adverse drug reactions the incidence is intolerable. Therefore, we encourage the commentator to focus on the main thesis of our study, that is to improve pharmacovigilance through causality assessment and to identify individuals at risk for ADR prior to medication, as was recently reported by us for paracetamol (see Borlak et al., Genome Medicine 2013, 5(9):86).

On 2014 Nov 08, Dirk Wetzel commented:

Basic epidemiological terms should be used correctly

I respectfully disagree with the methods and conclusions of this publication. The article suggests that an incidence of flupirtine-related hepatobiliary adverse events of “1:100,000 …or 0.8 in 10,000” has been calculated. In fact, this "incidence" is based on reported cases only. The estimated number of unreported cases might be as high as 90 to 95%, because considerable under-reporting is a well-known phenomenon of spontaneous reporting. Incidence rate is clearly defined as the number of new cases of a certain condition in relation to the population at risk within a specified period of time. As the authors used the number of reported cases as numerator (“new cases”), this method probably leads to a dramatic under-estimation of the potential risks associated with flupirtine. This could be interpreted as downplaying the risks of flupirtine.

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 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 2016 Apr 05, Leigh Jackson commented:

The authors state (I have omitted text references):

"Four commonly held tenets among acupuncturists regarding electrodermal activity (EDA) at acupuncture points are: (1) acupuncture points have lower electrical resistance than surrounding skin; (2) pathology-related acupuncture points are distinguishable from non-pathology-related acupuncture points; (3) changes in electrical skin resistance or conductance at acupuncture points correlate with acupuncture treatments and with the persistence of, or recovery from, disease; and (4) changes in EDA at acupuncture points occur when substances that are either therapeutically beneficial or toxic to an individual are placed in the electrical circuit with that individual.For more than 50 years these widely-held assumptions have formed the basis for the use of electrodermal devices in clinical practice, yet scientific studies to support these beliefs are sparse and methodologically diverse. The first tenet was comprehensively evaluated by Ahn et al in a recent systematic review. This review found preliminary evidence to suggest that acupuncture points and meridians may be electrically distinguishable from non-acupuncture point and non-meridian tissue. The latter three tenets, however, have yet to be rigorously examined."

If (1) could be scientifically shown to be true, then the other tenets would become a credible prospect. Is (1) scientifically credible? What might explain such a state of affairs? The safest bet as regards the data examined by Colbert et al. is the null hypothesis. Without powerful evidence to support (1) and with no scientific explanation as to why (1) should be true, the other three tenets will require extraordinarily powerful evidence to convince sceptics.

The first tenet must be scientifically established before the others have a chance to run. Otherwise it is piling weak evidence on top of weak evidence, conjecture on top of conjecture. A house of cards is being built on a pre-scientific foundation.

On 2014 Mar 21, Pedro Reche commented:

In this manuscript, we predicted that the MHCI-like protein MR1 will have an empty groove.However, a recent report have shown that MR1 binds vitamin B metabolites (PUBMED: 23051753). Therefore, we have updated our models including that information and repeated the manuscript predictions. With the exception of MR1, all of the predictions remain the same. Prediction of the ligand-type specificity of classical and non-classical MCH I molecules with the updates models is available for free public use at http://imed.med.ucm.es/MHCLIG/

On 2016 Dec 02, Aurélie Névéol commented:

The annotated data sets are now available at https://perso.limsi.fr/neveol/DepositionDataSets.zip

On 2015 Jul 10, Egon Willighagen commented:

Because Google Code is closing down [0], the source code repository is now available from GitHub: https://github.com/semanticchemistry/semanticchemistry

0.http://google-opensource.blogspot.jp/2015/03/farewell-to-google-code.html

On 2013 Jun 15, Steven Salzberg commented:

A very important study looking at long-term use of supplements, which revealed the surprising finding that risk of death increases with regular use of vitamin supplements. Bad news for supplement manufacturers, but important news for anyone who has been taking multivitamins thinking it can't hurt.

On 2014 Sep 02, M Mangan commented:

I used this data to build a 3D-printable version of the structure: http://3dprint.nih.gov/discover/3dpx-000579 .

On 2014 Jan 31, Huiqi Qu commented:

Adiponectin/leptin ratio is suggested as a useful biomarker for metabolic syndrome by this study.

On 2014 Sep 30, Dale D O Martin commented:

Several of the proteins identified in this paper, including MACF and CD-IC2 have recently been confirmed endogenously in Thinon et al found here http://www.ncbi.nlm.nih.gov/pubmed/25255805

On 2014 Feb 07, Dale D O Martin commented:

We have since shown that caspase-cleavage of HTT releases an autophagy-inducing domain that requires its post-translational myristoylation. http://www.ncbi.nlm.nih.gov/pubmed/24459296

Videos can be seen here: http://hmg.oxfordjournals.org/content/early/2014/01/22/hmg.ddu027/suppl/DC1

On 2017 Jun 27, 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.08997) and the results of the experiments were published in a Replication Study (http://dx.doi.org/10.7554/eLife.25306).

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 NCT0016012. We believe the correct ID, which we have found by hand searching, is NCT00160121.

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 Oct 23, Toby Gibson commented:

LATS protein kinases function in the Hippo signalling system. They are basophilic kinases known to phosphorylate sites that match Hx[Rk]xx[ST] motifs. The requirement for a His residue marks out LATS from other AGC group basophilic kinases. LATS substrate proteins usually have multiple matches to these motifs, as for example YAP1 (human) and SSD1 (yeast). In these proteins the LATS P-sites are in regions of natively disordered polypeptide.

The LATS substrate reported here, Snail1 does have two matches to the LATS site as shown in Fig. 3

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252572/figure/f3/

But these lie within DNA-binding zinc finger domains. The His residues are part of the zinc coordinating residues that hold the domain in a folded conformation. So long as the zinc fingers are folded, these His sidechains are unavailable to access a kinase active site cleft. Indeed all the residues in the proposed site(s) are in alpha helices when the zinc fingers are folded. The H, R and T residues are conserved in many other zinc finger proteins. If Snail1 zinc fingers can be phosphorylated by LATS then many other zinc finger proteins should also be targets. Because of the restricted focus of the HIPPO signalling pathway and the limited number of known LATS substrates in fly, yeast and mammal systems, this might be unlikely.

In the absence of biophysical data showing that the Snail1 sites can become accessible under plausible phosphorylation conditions, they are considered to be false positive sites in our ELM resource entry for LATS kinases

http://elm.eu.org/elms/elmPages/MOD_LATS_1.html

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 Aug 07, Randi Pechacek commented:

Jonathan Eisen used this paper as inspiration to write a blog post on microBEnet discussing the microbiomes of dishwashers.

On 2013 Dec 24, Kenneth Witwer commented:

As of April, 2014, published studies of dietary xenomiR transfer include the following (excluding reviews, in order of publication, and with public availability of high-throughput sequencing data noted if applicable):

This study: High-throughput sequencing (HTS) mapped up to tens of thousands of reads per million of specific plant microRNAs in human circulation; similar results in bovines; functional consequences for cholesterol metabolism in mice; public data availability not reported.

Zhang Y, 2012: analysis of >80 public HTS datasets; found uptake of few microRNAs; suggested contamination or other artifact(s) as explanation of miR168a detection; publicly available datasets identified in article.

Wang K, 2012: HTS, single digit reads per million of MIR168 in human circulation; public data availability not reported.

Wang K, 2013: HTS, fractional reads per million of MIR168 in murine circulation; public data availability not reported.

Snow JW, 2013: qPCR, little or no measurable uptake of dietary plant and/or animal microRNAs by humans, mice, and adult bees.

Witwer KW, 2013: qPCR, no response to dietary intake in a small primate feeding study; reportedly non-specific low-level amplification.

Dickinson B, 2013: HTS and qPCR; as mentioned by M Mangan, mouse replication study with negative results; data submitted to NCBI SRA as SRP028401.

Tosar JP, 2014: analysis of data and datasets; interpreted correlation between plant RNAs in original study findings and in a study of Amphioxus by the same group as evidence of contamination and "non-dietary" origin.

On 2013 Nov 16, M Mangan commented:

An attempt to replicate the claims in this paper has been published here: Dickinson B, 2013. The researchers were unable to make the same observations.

There's also an interesting backstory to the publication of the replication paper which you can find here: Anonymous, 2013.

On 2014 Mar 26, Wei-An (Andy) Lee commented:

In the safety-net clinic in Los Angeles, I find that premix insulin can be a great way to start patients. It reduces the initial burden of insulin initiation.

On 2014 Jan 08, Tom Kindlon commented:

References:

[1] Ross SD, Estok RP, Frame D, Stone LR, Ludensky V, Levine CB: Disability and chronic fatigue syndrome: a focus on function. Arch Intern Med 2004, 164:1098-1107.

[2] White P, Goldsmith K, Johnson A, Potts L, Walwyn R, Decesare J, Baber H, Burgess M, Clark L, Cox D, 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, 377:823-836.

[3] Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A: The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med 1994, 121:953-959.

[4] NICE: Chronic fatigue syndrome/Myalgic encephalomyelitis (or encephalopathy); diagnosis and management. National Institute for Health and Clinical Excellence (NICE); 2007.

[5] Rapport d’évaluation (2002-2004) portant sur l’exécution des conventions de rééducation entre le Comité de l’assurance soins de santé (INAMI) et les Centres de référence pour le Syndrome de fatigue chronique (SFC). 2006. http://www.inami.fgov.be/care/fr/revalidatie/general-information/studies/study-sfc-cvs/pdf/rapport.pdf . Accessed September 16, 2011 (French language edition) [6] Evaluatierapport (2002-2004) met betrekking tot de uitvoering van de revalidatieovereenkomsten tussen het Comité van de verzekering voor geneeskundige verzorging (ingesteld bij het Rijksinstituut voor Ziekte- en invaliditeitsverzekering) en de Referentiecentra voor het Chronisch vermoeidheidssyndroom (CVS). 2006. Available online: http://www.inami.fgov.be/care/nl/revalidatie/general-information/studies/study-sfc-cvs/pdf/rapport.pdf Accessed September 16, 2011 (Dutch language version)

[7] Stordeur S, Thiry N, Eyssen M. Chronisch Vermoeidheidssyndroom: diagnose, behandeling en zorgorganisatie. Health Services Research (HSR). Brussel: Federaal Kenniscentrum voor de Gezondheidszorg (KCE); 2008. KCE reports 88A (D/2008/10.273/58) [The main link seems to (temporarily?) not to work on the Belgium government website; it can be seen combined with another file at: http://bit.ly/t6GxcN ; alternatively it is on its own at: http://sacfs.asn.au/download/ReportCFS-NL.pdf ]

[8] White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; PACE trial group. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurol. 2007 Mar 8;7:6.

[9] White PD, Goldsmith KA, Johnson AL, Walwyn R, Baber HL, Chalder T, Sharpe M, on behalf of the coauthors. The PACE trial in chronic fatigue syndrome - Authors' reply. The Lancet - 28 May 2011 ( Vol. 377, Issue 9780, Pages 1834-1835 ) DOI: 10.1016/S0140-6736(11)60651-X

[10] Tiersky LA, DeLuca J, Hill N, et al. Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome. Appl Neuropsychol. 2001;8:41-50.

[11] Vercoulen JH, Swanink C, Fennis J, Galama JM, van der Meer JW, Bleijenberg G. Dimensional assessment of chronic fatigue syndrome. J Psychosom Res. 1994; 38:383-392.

[12] Dyck D, Allen S, Barron J, et al. Management of chronic fatigue syndrome: case study. AAOHN J. 1996;44:85-92.

[13] Marlin RG, Anchel H, Gibson JC, Goldberg WM, Swinton M. An evaluation of multidisciplinary intervention for chronic fatigue syndrome with long-term follow-up, and a comparison with untreated controls. Am J Med. 1998;105:110S-114S.

[14] Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. BMJ. 1997;314:1647-1652.

[15] Akagi H, Klimes I, Bass C. Cognitive behavioral therapy for chronic fatigue syndrome in a general hospital: feasible and effective. Gen Hosp Psychiatry. 2001;23:254-260.

[16] Sharpe MC, Archard LC, Banatvala JE, et al. A report--chronic fatigue syndrome: guidelines for research. J R Soc Med. 1991 Feb;84(2):118-21.

[17] Darbishire L, Seed P, Ridsdale L. Predictors of outcome following treatment for chronic fatigue. Br J Psychiatry. 2005 Apr;186:350-1.

[18] ICD-10. The ICD-10 classification of mental, and behavioral disorders. Geneva, World Health Organization, 1992.

On 2014 Jan 08, Tom Kindlon commented:

Productivity costs may not drop dramatically when CFS patients avail of current services

The authors appear to do a reasonable job, given the limits of the data available to them, in calculating the productivity costs before Chronic Fatigue Syndrome (CFS) patients reach the services in the UK. However, the reader is left with the impression that the productivity costs will drop dramatically once the patient reaches the services: "We had no data with which to assess the rate at which people with CFS/ME recover and return to work, either with or without specialized treatment. According to a systematic review of the literature, the proportion of adults in employment increased following interventions for CFS/ME (individualised rehabilitation, cognitive behavioural therapy and exercise therapy) and decreased in observational studies with no intervention [1]. Evidence from a recent evidence trial of cognitive behavioural therapy and graded exercise therapy indicated a recovery rate of 30-40% one year after treatment [2]."

However it may not be the case that the therapy offered in UK clinics (or in similar clinics elsewhere) will reduce the productivity costs by much if anything.

It is interesting to consider what happened in Belgium where rehabilitation clinics for patients satisfying the same CFS criteria [3] were treated using cognitive behavioural therapy (CBT) and graded exercise therapy (GET), the same therapies recommended for use in the UK [4]. Extensive external audits were performed there on these (Belgian) clinics. The main reports are in French and Dutch [5,6]; however, for those who can't understand either of those languages, a five-page summary is available in English [7]. It says, "Employment status decreased at the end of the therapy, from an average of 18.3% of a 38h- working week, to 14.9% [...] The percentage of patients living from a sickness allowance increased slightly from 54 to 57%."

Collin and colleagues claim, "Evidence from a recent evidence trial of cognitive behavioural therapy and graded exercise therapy indicated a recovery rate of 30-40% one year after treatment [9]." However, although a recovery measure was included in the trial's protocol[8], the authors have made clear [10] that no recovery rate was reported in the Lancet paper [9]: "[i]t is important to clarify that our paper did not report on recovery; we will address this in a future publication."

Collin and colleagues also say, "[a]ccording to a systematic review of the literature, the proportion of adults in employment increased following interventions for CFS/ME (individualised rehabilitation, cognitive behavioural therapy and exercise therapy) and decreased in observational studies with no intervention [1]." This is indeed mentioned in the abstract of the review. However, when one reads the paper, the data on which this is based is very limited: 2 longitudinal studies reported employment at both times with no interventions[10,11], 2 rehabilitation programs [12,13], one trial of GET [14] and one trial of CBT[15].

The figures for the GET study are for everyone (n=66) who was in the trial so include the people who were in the other arm of the trial (flexibility exercises and relaxation therapy) who then chose to do GET. So not those who had GET alone. This trial used the Oxford criteria [16] to define CFS, criteria which only requires the symptom of fatigue rather than the other symptoms required in the Fukuda criteria [3]. A study of those with fatigue has shown that satisfying the Fukuda CFS criteria [3] was the most powerful predictor of poor response to either GET or CBT [17]. So one cannot be extrapolate from such studies that those satisfying the Fukuda criteria, who are the group that Collin studied (and the group who used the Belgian clinics), will have the same improvements in employment measures.

Similarly, the trial of CBT [15] didn't use the Fukuda criteria - patients either satisfied the Oxford criteria [16] or else criteria for F48.0 (Neurasthenia) [18] i.e. they didn't all satisfy CFS criteria at all. Employment data was only available for 51 of the 80 individuals who started CBT (64%).

Finally, in one of the rehabilitation trials quoted [12], only two individuals took part it (at baseline neither was in employment but at follow-up, one of the two was). All in all, the evidence that CBT, GET and similar interventions will increase productivity is not strong. If governments, and those involve in providing health services, want to decrease the costs associated with CFS, throwing more and more money at CBT/GET services may not be the answer; other methods of treating the condition should be investigated. As the authors have shown, costs associated with the condition per individual are substantial, so more expensive therapeutic strategies can be justified on cost grounds alone.

On 2017 Apr 02, Christine Carson commented:

There was a follow-up to this article. The full text of the response (in Swedish) is available free from Lakartidningen website http://www.lakartidningen.se/07engine.php?articleId=18503

The full text of the response (in English) is available free from ResearchGate website at https://www.researchgate.net/publication/315738411_Carson_et_al_2012_Lakartidningen_English_20130626

On 2015 Aug 12, Tom Kindlon commented:

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

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)).

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 2015 Aug 12, Jim Woodgett commented:

A direct quote from reference 9 (referring to the source of the GIN inhibitor used here):

"A similar assay measuring inhibition of GSK3-alpha was also routinely run, but 7-12 showed no significant ability to discriminate between the two isoforms of GSK3 (data not shown). To the best of our knowledge, no isoform specific inhibitors of GSK3 have been reported, probably due to their high sequence homology (vida supra)."

This inhibitor (GIN) acts equally on both isoforms of GSK-3 (alpha and beta) and should not be referred to as a GSK-3beta selective inhibitor. This makes sense given that inhibition of GSK-3beta alone is insufficient for deregulation of beta-catenin (PMID: 17543867).

On 2014 Nov 14, Christopher Southan commented:

A 2014 abstract from Novartis http://www.alzheimersanddementia.com/article/S1552-5260(14)01380-6/fulltext quotes "Bace1/2 inhibition does not regulate TMEM27 cleavage and has no impact on pancreatic β-cell function and mass in diabetic mice". Lets hope new PubMed results can resolve this controversy.

On 2013 Dec 09, John Cannell commented:

The authors report that immune system dysregulation is common in autism spectrum disorder (ASD). The question is why does this immune dysregulation occur and what has caused such dysregulation to skyrocket in recent decades?

Vitamin D deficiency produces very similar immune dysregulation to what the authors reported.

Prietl B, 2013

Kamen DL, 2010

Yang CY, 2013

Baeke F, 2010

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, 2014

Meguid NA, 2010

Mostafa GA, 2012

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

DeLuca GC, 2013

Eyles DW, 2013

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

Cannell JJ, 2010

Cannell JJ, 2008

70% of American toddlers do not take the American Pediatric Association's recommended vitamin D supplement of 400 IU/day and few toddlers or pregnant women get any sunshine due to the sun scare. As vitamin D fortified milk consumption and sun exposure has declined, so have toddlers and pregnant women’s vitamin D levels. The dramatic increase in the incidence of ASD occurred during the same time vitamin D levels were falling in toddlers and pregnant women.

Some autism researchers seem cognizant of the entire body of autism research. For example, a group of well-known European ASD researchers, including Professor Christopher Gillberg of the Gillberg Neuropsychiatric Institute, have recently called for the need for “urgent research” into the vitamin D deficiency theory of ASD.

Kočovská E, 2012

As the authors point out, immune dysregulation is common in ASD. The question is why now and what is causing it?

John J Cannell, MD

Vitamin D Council

http://www.vitamindcouncil.org

On 2013 Oct 28, Konrad U Förstner commented:

Unfortunately the content of the zip file which can be downloaded from the given URL (http://www.mediafire.com/FengLi/2DGelsoftware) is password protected.

On 2016 Jan 11, Brian Wasko commented:

Cholesterol levels are a major risk factor for cardiovascular disease, which is the number one cause of death in the USA. The most commonly prescribed cholesterol lowering drugs are known as statins (e.g., Lipitor), which work by inhibiting cholesterol biosynthesis. Despite their success, statins have many side-effects that are likely due to the fact that statins inhibit not only cholesterol biosynthesis, but also synthesis of other important non-sterol compounds (e.g., Coenzyme Q10, Heme A, and prenylated proteins). By adding an inhibitor of squalene synthase in combination with either a statin or a nitrogenous bisphosphonate, I found that this appears to inhibit cholesterol synthesis more specifically than statins, and prevents the depletion of non-sterol compounds (the undesired effect of statins). This work was a proof of principle, and provides rationale to further develop these inhibitor combinations in order to create drugs superior to statins.

On 2017 Aug 06, Fernando Castro-Chavez commented:

Dear Reader, in this work I was able to discover that the methodological linkers are able to self-anneal, escaping in such a way the enzymatic digestion while contaminating thousands of sequences in the Genbank with their undigested fragments while binding together two independent and separate segments of genetic sequence; the most common linkers or adaptors and their annealing, are presented as well as advice on how to recognize and eliminate such false sequences produced by the methodological technologies in use to multiply in vectors the genetic sequences. Sincerely, Fernando Castro-Chavez.

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 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.07072) and the results of the experiments were published in a Replication Study (http://dx.doi.org/10.7554/eLife.21253).

On 2017 May 02, Peter Lorenz commented:

Though the figures and the tables in the supplement contain the (probably correct) label TIF1B for an interaction partner of the HP1 proteins, the text says "TIF1alpha"! TIF1B_HUMAN in Uniprot is TIF1beta/TRIM28. This discrepancy is confusing things since TIF1alpha/TRIM24 can also interact with HP1 proteins.

On 2013 Nov 15, Nikolaos Kokras commented:

Relates to Kokras N, 2011

On 2014 Jan 29, Amanda Capes-Davis commented:

I found this a very helpful review of breast cancer cell lines and their appropriate use in research.

On 2016 Nov 15, John Roger Andersen commented:

Read publishers pdf version in ReaderCube for free: click here.

On 2014 Mar 09, Gyanshankar Mishra commented:

We have also done a study on Tuberculosis management In India: Mishra G, Mulani J. Tuberculosis Prescription Practices In Private And Public Sector In India. NJIRM. 2013; 4(2): 71-78. Available online at http://www.scopemed.org/?mno=36915

Our other study highlights the fact of how drug resistant TB is created under programmatic management of TB in India: Gyanshankar Mishra, S V Ghorpade, Jasmin Mulani (2014) XDR-TB: An outcome of programmatic management of TB in India. Indian Journal of Medical Ethics 11: 1. 47-52 Jan-Mar.Available online at http://216.12.194.36/~ijmein/index.php/ijme/article/download/932/2179

Full text article Available online at http://www.ijme.in/index.php/ijme/article/view/932

On 2016 Feb 16, Gary Goldman commented:

In this second study published 8 months following the first, Moro et al. noted 121 spontaneous abortion (SAB) and 19 stillbirth (SB) reports or a total of 140 fetal-loss reports to VAERS during the first 5 months of the 2009/2010 influenza season. This equates to greater than 57 reports per million (>140/2,437,113) vaccinated pregnant women. The ratio of the 140 fetal-loss reports during the incomplete 2009/2010 season to the 1.21 reports/year representing the mean of the 19 prior seasons, yields a 116-fold (140/1.21) increase in fetal-loss reports (SAB and SB) in the VAERS database. Moro et al. attributed this dramatic increase, in part, to reporting bias, citing a "Weber-like effect." The Weber effect is a temporal reporting pattern whereby the number of reported adverse events (AEs) for a new drug increases during the first 2 years of marketing and then subsequently declines, presumably reflecting decreased enthusiasm for reporting as AEs become well known.

Despite the statistically significant rate ratio (RR) of 29.4 (95% confidence interval (CI): 19.0–45.8) for 2009/2010 fetal-loss report rate (57 reports/1 million) to the mean rate of 1.9 reports/1 million (over the previous 19 influenza seasons), the second Moro et al. study concluded, "… H1N1 vaccination in pregnant women did not identify any concerning patterns of maternal or fetal outcomes."

That this large spike in fetal death case reports to VAERS during the 2009/2010 influenza season was unlikely a mere "Weber Effect" and indeed a concerning pattern among pregnant women is addressed in the Goldman GS study titled, Comparison of VAERS fetal-loss reports during three consecutive influenza seasons: Was there a synergistic fetal toxicity associated with the two-vaccine 2009/2010 season? Hum Exp Toxicol. 2013 May;32(5):464-75. doi: 10.1177/0960327112455067. Epub 2012 Sep 27. Goldman GS, 2013

A study using a different methodology by Brown and Austin was published in Toxicological & Environmental Chemistry 2012 Sept;94(8):1610-27. Maternal transfer of mercury to the developing embryo/fetus: is there a safe level? DOI:10.1080/02772248.2012.724574 http://www.tandfonline.com/doi/abs/10.1080/02772248.2012.724574 It concluded: "It is, therefore, critical that regulatory advisories around maximum safe Hg exposures account for pregnant women and secondary exposure that children in utero experience. This study focused on standardized embryonic and fetal Hg exposures via primary exposure to the pregnant mother of two common Hg sources (dietary fish and parenteral vaccines). Data demonstrated that Hg exposures, particularly during the first trimester of pregnancy, at well-established dose/weight ratios produced severe damage to humans including death. In light of research suggestive of a mercuric risk factor for childhood conditions such as tic disorders, cerebral palsy, and autism, it is essential that Hg advisories account for secondary prenatal human exposures."

On 2016 Feb 16, Gary Goldman commented:

None

On 2014 Mar 02, Joshua Gray commented:

The article doesn't mention whether the patient's blister was deroofed or whether dermabrasion/debridement was performed. (The article does mention that blisters larger than 2 cm in diameter should be debrided on page 72.) Can you please provide a little more detail about how the blister was treated?

Joshua Gray, Associate Professor of Chemistry, U.S. Coast Guard Academy

On 2014 Jul 17, Adam Jacobs commented:

There are a number of problems with this study, and I fail to see how the authors conclusions of "no major problems of feasibility or acceptability of randomisation were found" can be supported.

First, there is the question of feasibility. This study attempted to use 6 breast screening units. These units apparently volunteered for the study, so might be considered to be less likely to have feasibility problems than sites in general. Despite that, 1 of the 6 sites was unable to participate.

There were clearly also resource implications in managing the study, but only an informal description was given of increases in workload. With no attempt made by the authors to quantify the increased workload, it is hard to judge how it might impact on feasibility.

As for acceptability, it is not surprising that the authors found no problems, as they did not look for them. I could not find any mention of the study participants having been asked questions about acceptability.

While women who were invited to screening could have spontaneously reported concerns about acceptability if they felt sufficiently strongly (though it is hardly realistic to expect that more than a tiny minority would do so if not specifically asked), women who were not invited, who would still be included in the study in the control group in the main age extension trial, were given no such opportunity.

This study has therefore told us nothing about how acceptable the study participants found it to be included in a randomised trial without their consent.

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).

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 2016 Nov 21, ATUL BUTTE commented:

Wow, sorry for the delay in replying! Yes, you are correct. The correct data set is GDS1615. Apologies for this error.

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 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 2013 Nov 15, Nikolaos Kokras commented:

Relates to Kokras N, 2012

On 2017 Oct 19, Wanliang Shi commented:

Please see the response: https://www.nature.com/articles/s41598-017-06415-5

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 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 2014 Mar 12, George W Hinkal commented:

None

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

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=32669705&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=32669707&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 Dec 10, Kath Wright commented:

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

On 2014 Sep 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 Apr 10, Ivan Oransky commented:

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

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 11, Alexis Verger commented:

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

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 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 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 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 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 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 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 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 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 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 2013 Jun 22, Martin Fenner commented:

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

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 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 2015 Sep 04, David Vaux commented:

None

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 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 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 2014 Dec 17, Sean Ekins commented:

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

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 2013 Oct 27, Gary Mirams commented:

None

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 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 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 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 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 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 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 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 2014 Nov 23, Harri Hemila commented:

A manuscript version is available at handle

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 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 2016 Feb 07, Fang-Cheng Yeh commented:

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

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 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 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 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