14,839 Matching Annotations
  1. Feb 2018
    1. On 2014 Apr 01, Christopher Southan commented:

      An updated (2013) comparison of public bioactive chemistry databases is available as http://www.ncbi.nlm.nih.gov/pubmed/24533037


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    1. On 2017 Apr 01, Egon Willighagen commented:

      Tony, the current code uses Java applets, but these are no longer usable on modern browsers due to discontinued support. Do you have an updated approach to include spectra from ChemSpider in webpages as you describe in the paper?


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    2. On 2017 Apr 12, Antony J. Williams commented:

      None


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    1. On 2014 Jan 10, Helmi BEN SAAD commented:

      The third author name is "BEN SAAD H" not "SAAD HB".


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    1. On 2013 Dec 28, Tsuyoshi Miyakawa commented:

      The finding of elevated D2High receptors in the CaMKIIalpha heterozygous knockout mice is quite interesting, regarding the possiblity that these mice may serve as an animal model of schizophrenia or bipolar disorder. We pointed out the possibility in our paper before(Yamasaki N, 2008), though it was not cited in this paper. I'd like to add that the same KO mice also show decreased cellular activity in dentate gyrus, while it is increased in CA1 in hippocampus (Hattori S, 2013), which is also consistent with the hippocampus dysfunction hypothesis of schizophrenia (Tamminga CA, 2010).


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    1. On 2016 Jun 08, Jafar Kolahi commented:

      This article has been criticized at: Kolahi J, Bang H, Park JJ, Desbiens NA. CONSORT 2010 and Controversies Regarding Assessment of Blindness in RCTs. Dent Hypotheses 2010;1:99-105. doi:10.5436/j.dehy. 2010.1.00016.

      Full text is available via: https://www.researchgate.net/profile/Jafar_Kolahi/publication/49583226_CONSORT_2010_and_Controversies_Regarding_Assessment_of_Blindness_in_RCTs/links/0f2cd8bca299367d1640cfd0.pdf


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    1. On 2015 Aug 06, Carrie Price commented:

      Please correct the spelling of United States so that the article can be located through keyword searching.


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    1. On 2014 Sep 03, Matthew Katz commented:

      This phase III trial is a classic example of how combined modality therapy (radiation combined with medical therapy) can provide effective cure for laryngeal cancer with an organ-preserving approach that can mean a major difference in quality of life. Surgery still may be needed, but for patients with a good response chemoradiation can be an effective nonsurgical treatment. More recent studies have suggested that doing the two treatments together (concurrent therapy) is superior though the toxicity may also be higher Forastiere AA, 2003


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    1. On 2014 May 09, Madhusudana Girija Sanal commented:

      It is all about numbers! It is statistics which defines what cancer is! One reason is that all definitions are a matter convenience for humans to classify, work or learn. Definitions quite often cannot be ‘black and white’ and hence statistical approaches are wise. The author note that the sixth hall mark of six hallmarks defined by Hannan and Weinberg, that is “the ability to invade and metastasis” is the only ‘real’ hallmark of cancer. However it is known that everything moves around, invade and proliferate need not be a cancer- example is endometriosis. Giant-cell tumor of the bone is considered benign but can spread to other parts including the lungs. Moreover during embryonic development different cell lineages compete and invade each other. Winners proliferate secrete autocrine factors, attracts blood vessels, force defeated cells to apoptosis or even ‘eat’ them up. This is not cancer! So what can be the hallmark or defining features of cancer? What I am proposing is a preliminary outline which may be further modified by “Wiki” efforts to make it more accurate. The following conditions needs to be satisfied to define a cancer: 1) Non physiological rate of cell division. Non physiological rate is defined as a growth rate which is a statistical outlier spatially and temporally for a given type of cell and organism. 2) A change, genetic or epigenetic with reference to the healthy genome which is a statistical outlier spatially and temporally for a given cell type and organism. Healthy reference genome and epigenome may be defined as the genome of individuals which satisfy two conditions a) falling within the statistically defined normal range of anatomical and physiological parameters for a population b) demonstrated longevity above 99.9 percentile of the population of a given organism.

      Cancer is a dynamic process-continuous evolution and selection. It is often,but not mandatory (at least theoretically) to be started by or seeded by a mutation and 'nurtured' or maintained by epigenetics. This is because epigenetic modification are faster as well as reversible. The effect of environment is mediated often (through cytokines, microRNA or even by physical factors) through epigenetic adaptations.Sooner or later more mutations and epigenetic changes accumulate during evolution and selection. This process is accelerated by chemotherapy (especially when using alkylating agents) radiation. Very specific and interesting mutations can evolve during targeted therapy (example-nilotinib).


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    1. On 2014 Feb 13, David Keller commented:

      The April 2010 Resident's Clinic discussed a 38-year-old woman with a history of gastric bypass who presented with profound anemia due to severe copper deficiency. She was noted to have an abnormally high zinc level. Her copper deficiency was attributed mainly to malabsorption due to her bowel surgery, and it was also noted that high zinc levels may induce copper deficiency. The question then arises as to why her zinc level was so high. The only clue is that the patient "had a history of frequent upper respiratory infections". Unfortunately, she was not asked whether she had used any of the over-the-counter zinc lozenge products which are sold as alternative sore throat remedies (for example "Cold-Eze"). Clinicians should not neglect to inquire about such non-prescription remedies or supplements when taking a patient's medication history, as important information may be learned.


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    1. On 2014 Sep 06, Ryan Radecki commented:

      Post-publication commentary: "The Most Dangerous Holiday!"

      Here in the United States, it is Labor Day – a Federal holiday established in 1886 by U.S. President Grover Cleveland. We, apparently, have Canada to thank for this innovation.

      But, what was actually news to me – Labor Day is actually the highest-volume holiday for pediatric trauma, outpacing all other holidays. I’d have thought 4th of July – with it’s various explosive devices – would be the most popular pediatric trauma holiday, but, between 1997 and 2006, Labor Day takes the lead, followed by Memorial Day, and 4th of July as a close third. Halloween, Easter, Thanksgiving, New Year’s and Christmas round out the list, in that order.

      http://www.emlitofnote.com/2014/09/the-most-dangerous-holiday.html


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

      Dear Reader, Here is where I did the discovery for the first time that by using the rotating circular classic representation of the genetic code, a series of resonances were able to be found, such as that every 90 degrees we had the hydrophobic amino acids per each quadrant, and the same applies when studying the rest of the properties of the amino acids, there is resonance for the basic, and for the hydrophobic amino acids, as well as for the phosphorilatable ones. This lead me to discover the rules of variation, that equivalent amino acids, produced by equivalent codons allow for the equally functional diversity of proteins and enzymes making all the wonderful array of varieties within each group of compatible organisms, which are the ones capable to interbreed producing a fertile offspring. Sincerely, Fernando Castro-Chavez.


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    1. 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.06959) and the results of the experiments were published in a Replication Study (http://dx.doi.org/10.7554/eLife.17584).


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    1. On 2016 Nov 18, Morten Oksvold commented:

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

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

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

      This article should therefore no longer be cited.


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

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


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    1. On 2016 Aug 24, 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 NCT00018255. We believe the correct ID, which we have found by hand searching, is NCT01068210.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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


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    1. On 2013 Dec 31, Tom Kindlon commented:

      I had a response published: FINE trial for CFS. Missing data

      BMJ. 2010 Jun 9;340:c2990. doi: 10.1136/bmj.c2990. FINE trial for CFS. Missing data. Kindlon T. http://www.ncbi.nlm.nih.gov/pubmed/20534661 Kindlon T, 2010

      My original e-letter from which this was drawn can be read here: http://www.bmj.com/rapid-response/2011/11/02/missing-data


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    2. On 2015 Dec 24, Tom Kindlon commented:

      Step test data were subsequently published

      "There were no between group differences in any of the step test measures at 20 or 70 weeks"(1).

      Reference:

      Wearden AJ1, Emsley R. Mediators of the effects on fatigue of pragmatic rehabilitation for chronic fatigue syndrome. J Consult Clin Psychol. 2013 Oct;81(5):831-8. doi: 10.1037/a0033561.


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    1. On 2016 Nov 20, Morten Oksvold commented:

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

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

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

      This article should therefore no longer be cited.


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    1. On 2016 Mar 18, ZHONGMING ZHAO commented:

      My lab recently moved to the University of Texas Health Science Center at Houston. The database is now available at https://bioinfo.uth.edu/SZGR/.


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    1. On 2014 Jul 16, Egon Willighagen commented:

      The Chemistry Development Kit has an Open Source (LGPL) implementation of these fingerprints: http://cdk.sf.net/.


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    1. On 2013 Oct 28, Jamie Horder commented:

      A historical note: in January 2009, shortly before this study was due to be completed, it was terminated early on the instructions of the local Research Ethics Committee. The reason for this was that rimonabant had just been withdrawn from the European market due to concerns over the high prevalence of depression in users - ironically, the very phenomenon that motivated this study.


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    1. On 2016 Sep 19, Morten Oksvold commented:

      Please note that a rather extensive correction was published 7 December 2011: "The wrong images were mistakenly presented for day 3 for the wild-type and the racX ylmE double mutant in figure S4. The original and correct images are now shown. Also, the wrong image was presented for the mixture of L-amino acids in panel B of fig. S13 and has now been removed."

      In 2013, the Losick group published results showing that D-amino acids inhibited bacterial growth and the expression of biofilm matrix genes and that the strain they originally used to study biofilm formation (B. subtilis) has a mutation in the D-tyrosyl-tRNA deacylase gene, an enzyme that prevents the misincorporation of D-amino acids into protein (Leiman et al., 2013). In a B. subtilis strain, which has a working copy of this gene, D–amino acids did not inhibit biofilm formation. The conclusion from their study was that "the susceptibility of B. subtilis to the biofilm-inhibitory effects of D-amino acids is largely, if not entirely, due to their toxic effects on protein synthesis.

      Does that mean that they no longer see D-amino acids as a specific mechanism to disassemble biofilms in B. subtilis but rather as nonspecific inhibitors of growth in some genetic backgrounds?

      Leiman et al. (2013) make no comment on the ability of D-amino acids to inhibit biofilm formation in staphylococcus aureus and Pseudomonas aeruginosa, as claimed in this article. The whole concept of biofilm dissasembly by D-amino acids therefore appears confusing.

      It was recently published an article showing that D-amino acids do not inhibit biofilm formation in Staphylococcus aureus (Sarkar S and Pires MM, 2015).


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    2. On 2016 Oct 13, Ilana Kolodkin-Gal commented:

      The supporting material for this paper was corrected, and the source data were provided to the editors of the Science journal. As for D-amino acids and biofilm formation: Non-canonical D-amino acids are small molecules interfering with cross-linking and transglycosylation of the peptidoglycan (Lam et al., 2009; Cava et al., 2011), and have been shown to trigger biofilm disassembly (Kolodkin-Gal et al., 2010), without affecting planktonic growth. This observation was later reproduced in various model organisms, such as Staphylococcus aureus (Hochbaum et al., 2011; Sanchez et al., 2013), Pseudomonas aeruginosa (Yu et al., 2012; Sanchez et al., 2014), the plant pathogen Xanthomonas citri (Li and Wang, 2014) , Escherichia coli (Xing et al., 2015) and in mixed biofilms (Si et al., 2014), as well as in other models published in numerous more recent publications. Furthermore, in our group we have generated so far two independent peer-reviewed publications clarifying the mode of action of D-aa for biofilm inhibition: http://onlinelibrary.wiley.com/doi/10.1111/1758-2229.12346/abstract http://www.jove.com/video/54612/methodologies-for-studying-b-subtilis-biofilms-as- Lastly, we established a consistent and robust experimental framework to study the effect of these small molecules biofilm inhibitors (Bucher et al., 2016).


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    1. 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 NCT0027813. We believe the correct ID, which we have found by hand searching, is NCT00278135.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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


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    1. On 2015 Jan 16, Sebastien Moretti commented:

      The authors state that only RevTrans does not require "the amino acid alignment together with nucleotide sequences" as input. Also ProtoGene does not. Its purpose is to back-translate amino acid alignments/sequences without nucleotide sequences, only based on protein blast similarity.


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    1. On 2014 Dec 10, Kath Wright commented:

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


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    1. On 2014 Jul 31, Sandra Porter commented:

      I enjoyed the way the authors dissected the function of these proteins and posted some images and directions here Along came a spider to show how others could explore the structure.


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    1. 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 NCT00122184. We believe the correct ID, which we have found by hand searching, is NCT00132184.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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

      * 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


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    1. 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 NCT00527782. We believe the correct ID, which we have found by hand searching, is NCT00527787.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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


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    1. On 2013 Oct 28, John Cannell commented:

      The control group in this study was flawed. The authors used children undergoing outpatient tonsillectomies as controls. Such children are likely to have low 25(OH)D levels.

      Seventy-eight percent of Auckland children undergoing tonsillectomy had vitamin D insufficiency.

      Reid D, Morton R, Salkeld L, Bartley J.Vitamin D and tonsil disease--preliminary observations. Int J Pediatr Otorhinolaryngol. 2011 Feb;75(2):261-4.

      Also, 25(OH)D levels of children with ear infections were about one-half that of community controls.

      Cayir A, Turan MI, Ozkan O, Cayir Y, Kaya A, Davutoglu S, Ozkan B.Serum vitamin D levels in children with recurrent otitis media. Eur Arch Otorhinolaryngol. 2013 Mar 30.

      In addition, in a prospective study, lower serum 25(OH)D levels were associated with increased risk of laboratory-confirmed respiratory tract infections RTI in children.

      Science M, Maguire JL, Russell ML, Smieja M, Walter SD, Loeb M. Low serum 25-hydroxyvitamin D level and risk of upper respiratory tract infection in children and adolescents. Clin Infect Dis. 2013 Aug;57(3):392-7.

      As Molloy et al did not use community controls, they did not find lower 25(OH)D levels in children with ASD compared to controls but 3 studies of ASD and 25(OH)D using community controls have found significant differences.

      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.

      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.

      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.


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    1. On 2016 Aug 30, Ben Goldacre commented:

      This trial has the wrong trial registry ID associated with it on PubMed. The ID given is NCT00350855 - the correct ID is NCT00350389. This has been corrected in a subsequent correction published in the originating journal, but not in the PubMed metadata.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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 and this ID has been corrected within the journal itself; we hope that this trial’s text and metadata can also be corrected in PubMed.

      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


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    1. On 2018 Jan 03, Denise N Slenter commented:

      The information captured in Figure 1 and 2 of this article, is available as a machine readable pathway at the WikiPathways database (https://www.wikipathways.org/index.php/Pathway:WP3933). Figure 3 is available at WikiPathways as well (https://www.wikipathways.org/index.php/Pathway:WP4195). These pathways can be used for data analysis in e.g. Pathvisio (https://doi.org/10.1371/journal.pcbi.1004085) and Cytoscape (https://doi.org/10.1101/gr.1239303).


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

      In the paper, it was discovered that the aquatic higher plant (macrophyte) hornwort (other English names: rigid hornwort, coontail, coon's tail; the Latin name: Ceratophyllum demersum) immobilized gold (Au) nanoparticles after their addition to water. This is the first time it was shown that the nanoparticles of gold (Au) in substantial amount bind to the living biomass of the aquatic macrophyte (namely, Ceratophyllum demersum). The concentrations of Au were measured in the samples of the phytomass using neutron activation analysis (NAA). As a result of the binding and/or immobilization of the nanoparticles, the amount of Au in the samples of the phytomass increased manifold (by a factor of 430) above the background level of gold in the plant tissues. The increase was by two orders of magnitude. The new data added some new information to the modern vision of the multifunctional role of the biota in the migration of elements in aquatic ecosystems, and water self-purification. Also, the result added new information to the studies of interactions of Au with organisms that may contribute to new biotechnologies (namely, phytotechnologies to remove heavy metals from water). DOI: 10.1134/S0012496610020158. https://www.researchgate.net/publication/44634488_The_aquatic_macrophyte_Ceratophyllum_demersum_immobilizes_Au_nanoparticles_after_their_addition_to_water;

      Some additional key words: nanomaterials, sorption, biosorption, immobilization, environmental chemistry, biogeochemistry, water quality,


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

      DOI: 10.1134/S0012496610020158 ;


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    1. On 2014 Jan 31, 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 and additional nanomaterial characterizations 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=41418753&page=0&tab=ALL

      https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=41418752&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


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    1. On 2014 Sep 06, David Keller commented:

      Are melanoma patients with pre-existing autoimmune disease at increased risk of severe immune reaction to ipilimumab?

      Patients with pre-existing autoimmune disease were excluded from this clinical trial. Even so, Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab. Is the rate of immune-related adverse events (IRAE) even higher in patients with pre-existing autoimmune disease who are treated with ipilimumab for melanoma? Clinical trials of immune checkpoint inhibitors all exclude such patients, but post-approval data on adverse events could supply an estimate of their relative risk ratio (RRR) with the following equation:

      RRR = ( IRAEp / IRAEt ) / (prevalence of AIDM)

      where RRR is the relative risk ratio for a severe adverse event in a melanoma patient with preexisting autoimmune disease who is treated with ipilimumab, and IRAEp is the number of immune related adverse events in patients with prior autoimmune disease, IRAEt is the total number of reported immune related adverse events, and the denominator is the prevalence of autoimmune diseases in melanoma patients.

      If patients with preexisting autoimmune disease are found to have a significantly elevated relative risk ratio for severe autoimmune reactions to ipilimumab compared with other melanoma patients, they should have access to that information in order to help them make difficult treatment decisions. Each melanoma patient will have their own cut-off of acceptable values for RRR.

      Recently, an anti-PD1 immune checkpoint inhibitor, pembrolizumab, was approved by the FDA for advanced melanoma patients who have failed on ipilimumab. It has been suggested that the anti-PD1 agents have a milder autoimmune adverse event profile than anti-CTLA-4 agents like ipilimumab (1,2). If this is true, it may be a reason for patients with active autoimmune diseases to be treated with the former, skipping the latter. If the RRR for a patient with preexisting autoimmune disease is found to be 5, 10 or even 20 times higher than for average patients, then this data could be used to justify treating them with pembrolizumab first-line and off-label.

      This question cannot be answered using data from the controlled clinical trials, because patients with active autoimmune diseases were excluded from these studies.

      When the FDA approved Yervoy (ipilimumab) in 2011, they mandated a risk mitigation program, including a database of all reported post-approval adverse reactions to Yervoy. In order to obtain full access to the information in that database, one must file a separate request with the FDA, under the Freedom of Information Act (FOIA), for each reported adverse reaction. The number of reports of serious adverse events associated with Yervoy filed from March 2011 through September 2014 totals nearly 4000. Since the cost of filing an FOIA request for each report is over $50, the cost to perform a detailed analysis of the entire database of adverse events is over $20,000. This fee is prohibitive, and defeats the purpose of the risk mitigation program. FDA should provide free access to this data, in order to stimulate and facilitate research into the effects of Yervoy on patient populations which were excluded from the controlled clinical trials.

      References

      1: Weber J. Review: anti-CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events. Oncologist. 2007 Jul;12(7):864-72. Review. PubMed PMID: 17673617.

      2: Fecher LA, Agarwala SS, Hodi FS, Weber JS. Ipilimumab and its toxicities: a multidisciplinary approach. Oncologist. 2013 Jun;18(6):733-43. doi: 10.1634/theoncologist.2012-0483. Epub 2013 Jun 17. Review. PubMed PMID: 23774827; PubMed Central PMCID: PMC4063401.


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    1. On 2017 Sep 20, Jason Stajich commented:

      The CRISP software is current available at https://github.com/vibansal/crisp instead of the link in the dead link in the abstract.


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    1. On 2015 Apr 15, thomas samaras commented:

      None


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    2. On 2015 May 22, thomas samaras commented:

      Many conflicting studies exist that show shorter people have low coronary heart disease (CHD). Two review papers summarizing findings showing shorter people have less CHD than taller populations are cited below. For example, populations of short people (less than 5'5")that have virtually no CHD include the Solomon Islands, Papua New Guinea, Kalahari Bushmen, Congo Pygmies, and Kitavans. However, with Westernization, some are growing taller and heavier and seeing increases in CHD. Over the last few decades, the Japanese have held the top or third from top ranking for having the lowest CHD in the world.

      Women are shorter than men and have lower life-long mortality from CHD. The argument that smaller blood vessels contribute to CHD doesn't seem to apply to women.

      The World Cancer Research Fund (2007) has attributed our increased height, weight and chronic disease (including CHD)to our Western diet. They reported that today's chronic diseases are a relatively new occurrence. Trowell also reported that pre-Western people are generally free of Western chronic diseases, including CHD. Burkitt evaluated the medical records from almost 1000 hospitals in the non-developed world and found Western diseases (including CHD) were rare.

      The Laron dwarfs in Ecuador have been studied for over 20 years and were found to have no deaths from cancer and diabetes. They also have normal atherosclerosis in spite of being overweight and obese. About 70% of their deaths are from non-age related causes: alcoholism, infections, accidents and neurological disorders.

      It is hard to believe that shorter height per se is related to CHD since many studies show that shorter people live longer. These studies include populations in San Diego, Hawaii, Ohio, Spain, Sardinia, and Okinawa. See longevity studies cited below.

      Sources

      Samaras TT, Elrick H, Storms LH. Is short height really a risk factor for coronary heart disease and stroke mortality? A review. Medical Science Monitor 2004;10:RA63-76.

      Samaras TT. Shorter height is related to lower cardiovascular disease risk--a Narrative Review. Indian Heart Journal. 2013; 65: 66-71.

      He Q, Morris BJ, Grove JS, et al. Shorter men live longer: Association of height with longevity and FOXO3 genotype in American men of Japanese ancestry. PLOS ONE; 2014:9: 1-8.

      Samaras TT. Evidence from eight different types of studies showing that smaller body size is related to greater longevity. Journal of Scientific Research & Reports. 2014;3(16):2150-2160

      Salaris L, Poulain, Samaras. Height and survival at older ages among males born in an in-land village in Sardinia. Biodemography and Social Biology. 2012: 58(1): 1-13.

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


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

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

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

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


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    1. On 2015 Jul 21, Richard Jenner commented:

      Figure S3C of Davidovich C, 2015 shows that the apparent repressive effect of the Xist-RepA stem loop used as a control in Figure 6D of our paper Kanhere A, 2010 is actually due to a mutation of the construct promoter, which we had overlooked. As shown by Davidovich et al, correction of this mutation abolished the apparent repressive activity. Mutations were also found in the short RNA stem loop construct, however, although reduced, the repressive activity of this stem loop remained after these were corrected (Figure S3D of Davidovich C, 2015).


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    1. On 2014 Jan 08, Tom Kindlon commented:

      There is evidence that CFS patients don't engage in “boom and bust” activity patterns

      As Maes and Twisk highlight[1], one part of the Harvey and Wessely model is the contention that CFS patients engage in “boom and bust” activity patterns. This claim has been repeated so often by various individuals that it has been seen as fact by some. But is there actual evidence for it?

      What many people may not be aware of is we do have data on the issue. A Dutch study tested a relatively large cohort of CFS patients (n=277) along with 47 healthy controls [2]. The research used actometers to provide an objective measure of activity over 12 days. It found: "Compared to healthy controls, no indication was found that the CFS patients as a group were characterised by a high number of large day-to-day fluctuations in activity."

      References:

      [1] Maes M, Twisk FN. Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways. BMC Med. 2010 Jun 15;8:35.

      [2] van der Werf SP, Prins JB, Vercoulen JH, van der Meer JW, Bleijenberg G. Identifying physical activity patterns in chronic fatigue syndrome using actigraphic assessment. J Psychosom Res. 2000 Nov;49(5):373-9.


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    1. On 2014 Dec 10, Kath Wright commented:

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


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    1. On 2016 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 body of the text of the article. The ID given is NCT00028572. We believe the correct ID, which we have found by hand searching, is NCT00028574.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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

      * 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


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    1. On 2017 Mar 05, Boris Barbour commented:

      Readers may find the comments/discussion beneath a later paper of interest: Gomes JM, 2016


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    1. On 2017 Dec 06, University of Kansas School of Nursing Journal Club commented:

      Team Members: Samantha Gibbs, Alyssa Cruz, Annastasia Elliot, Sam Fankhauser, Kelli Fast & Dilnoza Hamraeva [Class of 2018]

      The article was selected because it demonstrates how nurse compassion satisfaction, job satisfaction, stress, burnout, and compassion fatigue are related to nurse caring. This relates to our class discussion about factors that are essential to creating a motivational work environment, specifically intrinsic motivators. As future leader, it is important to recognize what motivates others in order to help them grow as a professional nurse. This article explores the relationship between intrinsic motivation and nurse caring which has not been explored in our course.

      Intrinsic motivation is an essential aspect to caring for patients. If nurses are to fully advocate for and empower patients, they must be intrinsically motivated and have support from nurse leaders on their unit. This article was selected because the research findings confirm that motivational variables in the work environment are positively correlated with nurse caring and compassion. This increased caring results in overall improved patient care and increased patient satisfaction. The nursing leadership in a work environment is essential to cultivating motivation among staff nurses and must not be overlooked. While extrinsic motivation can be a good starting point, it is the goal that all nurses will eventually operate under conditions of intrinsic motivation, meaning that the nurses are coming to work and caring for patient because they find joy in it. The findings of this study illustrate that fostering a nurse’s intrinsic motivation can result in increased nurse caring behaviors, which will therefore increase patient satisfaction (Burston & Stichler, 2010). Burtson and Stichler state that it is the job of nurse managers to, “reawaken the source of satisfaction that nurses derive from caring, while improving their sense of social belonging” (2010, p. 1829).

      As student nurses on the brink of graduation, it is imperative to our professional identity that we understand the systems set in place that motivate workers before accepting a position as an RN. This will allow us as new graduate nurses to feel motivated and empowered in the microsystem and will lead to optimal patient care and increased patient and job satisfaction. Our job satisfaction and intrinsic motivation impacts us personally as well, as we aspire to enjoy work and care for patients in a holistic manner. Even if one is not in a leadership position, future nurses can contribute to the motivational environment by acknowledging coworkers’ achievements and challenging peers to promote growth and life-long learning. If staff nurses and nurse managers promote motivational work environments, the future of nursing practice will naturally begin to foster motivational techniques that will increase both nursing and patient satisfaction as results of improved patient care.

      Burston, P. & Stichler, J. (2010). Nursing work environment and nurse caring: Relationship among motivational factors. Journal of Advanced Nursing, 66(8), 1819-1831. doi: 10.1111/j.1365-2648.2010.05336.x


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    1. On 2017 Mar 05, Boris Barbour commented:

      Readers may find the comments/discussion beneath a later paper of interest: Gomes JM, 2016


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    2. On 2017 Mar 05, Boris Barbour commented:

      Readers may find the comments/discussion beneath a later paper of interest: Gomes JM, 2016


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    1. On 2016 May 03, Suresh Panneerselvam commented:

      This is very informative article. I enjoyed reading this. Thank you.


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    1. On 2014 Feb 28, William Gunn commented:

      This study has been chosen for replication by the Cancer Biology Reproducibility Project.

      The Cancer Biology Reproducibility Project is a collaboration between the Center for Open Science, Science Exchange, and Mendeley to replicate key experiments from 50 impactful cancer biology studies published between 2010-2012.

      To track the progress of this replication, please visit: https://osf.io/yyqas/

      To learn more about Cancer Biology Reproducibility Project, including the full list of 50 studies, how the studies were chosen, and details about the people who are managing the project, please visit: https://osf.io/e81xl/wiki/home/


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    1. 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 NCT00801358. We believe the correct ID, which we have found by hand searching, is NCT01334658.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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


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    1. On 2014 Jan 31, David Simpson commented:

      A minor question, but I noticed that a different composition was given for the 4-plex iTRAQ 115 label here in Figure 3 than was given in the classic iTRAQ paper: Ross et al., Mol. Cell. Proteomics 2004, 3, 1154–1169. Has the 4-plex iTRAQ 115 label composition been changed by the manufacturer since the first report was published?

      EDIT: To be clear, I'm not doubting the composition given here (it's supported elsewhere: Phanstiel et al., J. Am. Soc. Mass Spectrom. 2008, 19, 1255–1262). I'm just curious about the change from the earliest report.


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    2. On 2014 Feb 01, David Simpson commented:

      I'm intrigued by the concept discussed here that larger modifications might be inherently more difficult to identify using current search software. Comparing TMT 6-plex with the newer TMT 10-plex, which has the same mass shift, might shed some light on this problem.


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    1. 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.


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    1. On 2013 Dec 20, Raphael Stricker commented:

      Fatal Clostridium Difficile Colitis Following Treatment for Lyme Disease: The Wrong Message.

      Raphael B. Stricker, MD* and Lorraine Johnson, JD, MBA*

      *International Lyme and Associated Diseases Society, P.O. Box 341461, Bethesda, MD 20827-1461. www.ILADS.org

      Holzbauer and colleagues (1) describe a case of fatal Clostridium difficile colitis in a patient treated with ten weeks of oral antibiotics for chronic Lyme disease. Rather than focusing on patient-specific risk factors and prevention of antibiotic-related complications, the authors preach about the dangers of treating Lyme disease outside the controversial guidelines of the Infectious Diseases Society of America (IDSA), which were the subject of an antitrust investigation by the Connecticut Attorney General (2,3). In doing so, the authors exaggerate the risks of treating Lyme disease and ignore the risks of failing to treat an ongoing spirochetal infection that may cause disability equivalent to congestive heart failure, and even death (4,5). Consequently the emphasis of the case report is misguided and ultimately detrimental to patient care.

      In the single case described here, no information is given about cellular or humoral immune dysfunction that may have contributed to the rapid demise of the 52-year-old patient. This rapid demise is unusual in patients less than 80 years old with C. difficile colitis (6) and suggests the presence of a hypervirulent C. difficile ribotype that might explain the clinical course. Furthermore, the authors fail to mention whether the patient received probiotic therapy during the extended oral antibiotic treatment. Probiotic therapy appears to be effective in avoiding antibiotic-induced complications, and evidence suggests that certain probiotics may neutralize C. difficile toxin (7,8). The lack of probiotic therapy may have been a significant factor in this patient’s demise.

      As for the appropriateness of antibiotic therapy in a patient with clinical and laboratory evidence of chronic Lyme disease, two points should be considered. First, two approaches to treatment of this tickborne illness have been described in the medical literature. The approach promulgated by IDSA proscribes extended antibiotic therapy for persistent symptoms related to infection with Borrelia burgdorferi, the spirochetal agent of Lyme disease (2). In contrast, the competing approach of the International Lyme and Associated Diseases Society (ILADS) considers this therapy to be appropriate based on evidence of persistent spirochetal infection (4,9,10). Second, the patient described in the report received a course of oral antibiotics that is shorter than the antibiotic courses endorsed or accepted by IDSA for chronic conditions such as tuberculosis, leprosy, complicated actinomycosis, Whipple’s disease, Q fever endocarditis, alveolar echinococcosis, osteomyelitis and asplenia prophylaxis; the risks of prolonged antibiotic therapy are considered acceptable for these conditions (11-18). While several clinical studies have demonstrated the safety of extended oral and intravenous antibiotic therapy for patients diagnosed with Lyme disease (19-22), caution should always be exercised in administering extended antibiotic therapy to any patient with a chronic infectious disease.

      References

      1. Holzbauer SM, Kemperman MM, Lynfield R. Death due to community-associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected Lyme disease. Clin Infect Dis 2010;51:369-70.

      2. Johnson L, Stricker RB. The Infectious Diseases Society of America Lyme guidelines: a cautionary tale about development of clinical practice guidelines. Philos Ethics Humanit Med 2010;5:9.

      3. Johnson L, Stricker RB. Final report of the Lyme Disease Review Panel of the Infectious Diseases Society of America: A Pyrrhic victory? Clin Infect Dis 2010;51:1108-9.

      4. Cameron DJ. Proof that chronic Lyme disease exists. Interdiscip Perspect Infect Dis 2010;2010:876450.

      5. Centers for Disease Control and Prevention (CDC). Three sudden cardiac deaths associated with Lyme carditis - United States, November 2012-July 2013. MMWR Morb Mortal Wkly Rep. 2013;62:993-6.

      6. Kotila SM, Virolainen A, Snellman M, Ibrahem S, Jalava J, Lyytikäinen O. Incidence, case fatality and genotypes causing Clostridium difficile infections, Finland, 2008. Clin Microbiol Infect 2011;17:888-93.

      7. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 2006;101:812-22.

      8. Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C. Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect Immun 1999;67:302-7.

      9. Stricker RB. Counterpoint: Long-term antibiotic therapy improves persistent symptoms associated with Lyme disease. Clin Infect Dis 2007;45:149-57.

      10. Stricker RB, Johnson L. Lyme disease: The next decade. Infect Drug Resist 2011;4:1–9.

      11. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001;345:189-200.

      12. Cox H, Kebede Y, Allamuratova S, Ismailov G, Davletmuratova Z, Byrnes G, Stone C, Niemann S, Rüsch-Gerdes S, Blok L, Doshetov D. Tuberculosis recurrence and mortality after successful treatment: impact of drug resistance. PLoS Med 2006;3:e384.

      13. Garner JP, Macdonald M, Kumar PK. Abdominal actinomycosis. Int J Surg 2007;5:441-8.

      14. Freeman HJ. Tropheryma whipplei infection. World J Gastroenterol 2009;15:2078-80.

      15. Liu YH, Wang XG, Gao JS, Qingyao Y, Horton J. Continuous albendazole therapy in alveolar echinococcosis: long-term follow-up observation of 20 cases. Trans R Soc Trop Med Hyg 2009;103:768-78.

      16. Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials? Int J Infect Dis 2005;9:127-38.

      17. Price VE, Blanchette VS, Ford-Jones EL.The prevention and management of infections in children with asplenia or hyposplenia. Infect Dis Clin North Am 2007;21:697-710, viii-ix.

      18. Beytout J, Tournilhac O, Laurichesse H. Antibiotic prophylaxis in splenectomized adults. Presse Med 2003;32(28 Suppl):S17-9.

      19. Donta ST. Tetracycline therapy for chronic Lyme disease. Clin Infect Dis 1997;25 Suppl 1:S52-6.

      20. Donta ST. Macrolide therapy of chronic Lyme disease. Med Sci Monit 2003;9:PI136-42.

      21. Stricker RB, Green CL, Savely VR, Chamallas SN, Johnson L. Safety of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Minerva Med 2010; 101:1–7.

      22. Stricker RB, Delong AK, Green CL, Savely VR, Chamallas SN, Johnson L. Benefit of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Int J Gen Med 2011;4:639-46.

      Disclosure: RBS is a member of the International Lyme and Associated Diseases Society (ILADS) and a director of LymeDisease.org. He has no financial or other conflicts to declare.


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    1. On 2017 Jan 18, CHRISTOPH LANGE commented:

      The VEGAS/VEGAS2 software can provide p-values for the top-percentage statistic that are anti-conservative, as the computation of the null-distribution is incorrect. In our technical report, we discuss the issue and provide code that, if included in VEGAS/VEGAS2, will provide correct p-values.

      http://biorxiv.org/content/early/2017/01/17/101014


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    1. On 2014 Mar 18, Gwinyai Masukume commented:

      In Panel 1: Differential diagnoses in severe pre-eclampsia by organ system, malaria is not mentioned.

      In some settings, malaria is an important differential diagnosis of severe pre-eclampsia as it can have a significant overlap of clinical and laboratory features with severe pre-eclampsia, for example, headache, nausea, vomiting, intra-uterine growth restriction, thrombocytopenia and raised serum creatinine (1).

      Reference: (1) McGready R, Sot M, Ashley EA, Nosten F, Rijken M, Dundorp A. The diagnosis and treatment of malaria in pregnancy. guideline number 54(B). London: Royal College of Obstetricians and Gynaecologists, 2010.


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    1. 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 NCT00116932. We believe the correct ID, which we have found by hand searching, is NCT00116922.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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

      * 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


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    1. On 2014 Mar 02, Zhongheng Zhang commented:

      My first paper that is indexed in ISI web of science.


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    1. On 2014 Aug 18, Raha Pazoki commented:

      Meta-analysis for rs2824292

      For those interested, Meta-analysis of the discovery and replication set for the effect of rs2824292 on risk of ventricular fibrillation in this paper can be easily done using meta package in R. The result of the Meta-analysis shows a pooled odds ratio (O.R.) of 1.68 for rs2824292 in the fixed effect model (95% confidence interval [C.I.] = 1.43, 1.97; P value = 2.2×10<sup>-10</sup> ). The random effect model shows similar values (O.R. = 1.67; 95% C.I. = 1.42, 1.98 ; P value = 1.2×10<sup>-9</sup> ).


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    1. On 2016 Jan 08, 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. (2007) paper on the Georgia cohort (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 (3) 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 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.

      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. Ann Int Med 1994, 121:953-959.

      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


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    1. On 2015 Jul 18, Jan Tunér commented:

      In the paper by Kucuk, a laser of 250 mW was used for 48 seconds. This produces energy of 12 J. This parameter is not reported, only the dose of 12 J/cm2. Since the laser aperture is reported to deliver a spot of approximately 10 mm, the dose and the energy in this case gets almost the same numeric value. So far so good. The problem is the understanding of the therapeutic window for biostimulation. The authors cite other researchers and here the complications start. For instance, Hansson used 904 nm, 0.3 mW, 3 minutes. 0.3 x 180 = 0.054 J for clinical use. Mazetto used 780 nm, 70 mW, 10 s, 89.7 J/cm2 = 0.7 J for clinical use. Venanzio used 780 nm, 30 mW, 10 s, 6.3 J/cm2 at three TMJ points. 0.3 x 3 = 0.9 J. The energies in these studies have had to be recalculated since they are not reported in the papers. The three examples above are for TMD arthritic pain. The myalgic studies discussed in the Kucuk paper have the same problem. Now, looking at the energies used in the three studies above, these have been in the range 0.5 - 0.9 J per point. For an average human (keeping in mind that TMD appears to be more common in females) of 60 kg, this would mean approximately 0.2 J per kg. The mean weight of the rabbits was about 3 kg. The 12 joules applied brings 4 joules per kg. For humans this corresponds to 4 x 60 = 180 J! The Arndt-Schultz law stipulates that “For every substance, small doses stimulate, moderate doses inhibit, large doses kill.” The exact optimum for biostimulation of inflammation in the TMJ is not known, but the World Association for Laser Therapy recommends 1-2 points and a total energy of 4 J for clinical use. The TMJ is quite superficial whereas muscles require considerable higher energies due to the poor penetration into these well vasculated tissues. The power density (mW/cm2) is also of importance and low power and longer time are reported to be more effective for tissue repair than high power and short time, even using the same total energy. It is suggested that the lack of effect in the Kucuk paper is due to gross over dosage and subsequent inhibition.


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    1. 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 NCT0012281. We believe the correct ID, which we have found by hand searching, is NCT00122811.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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

      * 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


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    1. On 2014 Dec 10, Kath Wright commented:

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


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    1. On 2014 May 23, Morgan Price commented:

      According to the supplementary tables, the mRNA concentration from FISH is poorly correlated with the concentration from RNASeq or with the protein levels. This seems inconsistent with the analyses in Figure 3. In particular, the legend of Figure 3 reports a Pearson correlation of 0.77 between each gene's mRNA FISH level and its protein level. This calculation was done "for genes that express >100 copies of proteins per cell". But when I compute the same correlation coefficient, using the data in Supplementary Table 6, I get a correlation coefficient of just 0.35. (I used the columns "Mean_RNA FISH" and "Mean_Protein", and only the rows with Mean_Protein > 100 and with a Mean_RNA FISH value.)


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    1. On 2016 Jun 02, John Tucker commented:

      The authors of this paper undertook a survey of published results for trials conducted between January 2000 and December 2006. The results of this survey were that industry-only sponsored studies were more likely to obtain positive results than those partially funded by industry, and that these were in turn more likely to report positive results than those performed without industry funding. The results of this study have been widely cited as evidence that the results of industry funded studies are unreliable and tainted by bias.

      A fundamental difficulty with this type of analysis is the underlying assumption that the trials performed by industry and those performed without industry funding are substantially comparable. While the authors do not provide sufficient detail regarding their search criteria to allow perfect recapitulation, a search of the clinicaltrials.gov database with the term "hypercholesterolemia" turns up the following trials.

      *93 funded by industry alone, including 39 trials of statins and 32 trials of ezetimibe

      *7 funded jointly by industry and some other entity, including trials of orange juice, a high fat diet, and glucosamine as interventions

      *7 funded entirely by non-industry entities, including studies of garlic (2x), flaxseed (2x), a high protein diet (2x), and plant sterol-enriched tea as interventions.

      Given the vast gulf between the types of interventions being examined and their a priori likelihood of efficacy, the results of studies such as this one should be interpreted with caution.


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    1. On 2014 Oct 12, GianCarlo Panzica commented:

      Effect of the treatment on the vasopressin system of the paraventricular nucleus are described in a following paper: Grassi D, 2014


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    1. On 2017 Mar 05, Boris Barbour commented:

      Readers may find the comments/discussion beneath a later paper of interest: Gomes JM, 2016


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    1. On 2016 Dec 10, Arnaud Chiolero MD PhD commented:

      A comprehensive and bright review of principles of cancer screening. It offers insights on why intuition and common sense mislead health professionnals and patients about the supposed benefits of screening, and why an evidence-based approach is necessary in the assessment of potential benefits and harms of cancer screening.


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    1. On 2014 Dec 10, Kath Wright commented:

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


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    1. On 2013 Dec 27, Wichor Bramer commented:

      To be a useful addition to a search strategy, sensitive filters should not be too unspecific, and specific filters not too insensitive. Developing a sensitive filter of 100% is no problem, if specificity is not considered, very general filter will find all articles, whether they are positives or negatives, but does not add value to a search, because it does not limit the number needed to read (NNR). And a filter with 100% specificity is easy to create, by taking a very rare phrase that only occurs in one or two positives, but then the sensitivity is almost zero, and the filter is useless.

      Simon, Hausner, et al. developed sensitive filters for nurse staffing with a sensitivity of almost 100%, but with a precision of 0.3% the NNR is almost 300, and even for their precise strategy the NNR was 3, with a sensitivity of less than 50%. The authors conclude themselves that 'nurse staffing studies are difficult to identify', but that is true for almost every thematic issue. The low values their filters renders them useless in practice.

      The fact that the most precise filter contains the MeSH term Outcome and Process Assessment (Health Care) is related to the fact that this is part of the search strategy of one of the systematic reviews (Kane RL, 2007) that was used to gather the positives, a review of which the presented search strategy is very difficult to read and not repeatable. http://www.ncbi.nlm.nih.gov/books/NBK38310/


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    2. On 2014 Dec 10, Kath Wright commented:

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


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    1. On 2015 Oct 16, Anne Niknejad commented:

      There is an error on Table 1: inversion of gene names between plcA and plcC, plcA gene name should be Rv2351 (not Rv2349 as claimed), and plcC gene name should be Rv2349 (not Rv2351 as claimed)


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    1. On 2015 May 04, David Mage commented:

      This 1945 paper identified the prone sleeping position as a major risk factor for these infant deaths that were "entirely unexpected," that were first called SIDS by JB Beckwith in 1969. It took some 46 years for the medical profession to rediscover the prone position as a definitive risk factor for SIDS, when SM Beal and CF Finch published "An overview of retrospective case-control studies investigating the relationship between the prone sleeping position and SIDS." J Paediatric Child Health 1991;27:334-339. PMID:1836736

      Davison wrote about 318 infants dying in Birmingham, U.K., 1938-1944, as follows: "Quite a number of the children in all groups were found prone or with the face turned into the pillow -- borne out by post-mortem hypostasis -- suggesting death by obstruction to the air passages; and in the absence of other factors one might naturally conclude that death was caused by mechanical means." But that would be wrong because many of these deaths were "found to be respiratory or due to otitis media."


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    1. 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 NCT007919689. We believe the correct ID, which we have found by hand searching, is NCT00791986.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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


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    1. On 2016 Mar 20, Daniel Schwartz commented:

      The HEART SCORE can be calculated online or via a mobile application: http://qxmd.com/calculate/heart-score-chest-pain-in-the-er

      Conflict of interest: Medical Director, QxMD


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    1. On 2013 Oct 24, Robert Tibshirani commented:

      This paper presents the coordinate descent approach for fitting the lasso, elastic net, and other related models. It provides the basis for the widely-used glmnet R package

      http://cran.r-project.org/web/packages/glmnet/index.html


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    1. On 2014 Jan 29, Amanda Capes-Davis commented:

      It is really good to see publication of new, authenticated ATC cell lines. The STR data show clearly that these cell lines come from the expected donors. It should be noted though that the STR loci here are not widely used by laboratories worldwide. The ASN-0002 Standard, published by ANSI in 2012, now recommends a consistent set of eight STR loci for cell line authentication testing.


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    1. On 2014 Jan 11, Brett Snodgrass commented:

      Dear Authors,

      Thank you for publication of the excellent article that provides important knowledge about the incidence of VCCs in HLH and their effect on survival.

      Please consider that if the VCC results from pathologic alteration of an arterioluminal vessel, then the VCC may not be synonymous with sinusoid as there is no sinusoid involved.

      However, if the VCC results from pathologic alteration of an arteriosinusoidal vessel, then the term sinusoid would appropriately apply to only a segment of the VCC. The segment of the VCC closer to the epicardium is presumably derived from the "arterio" segment of the arterio*sinusoidal connection.

      VCCs are often used synonymously with VCACs.

      1. Ventriculocoronary connections (VCCs)

      2. Ventriculocoronary arterial connections (VCACs)

      Please provide your kind consideration to the following article published by Joseph Treolar Wearn in 1933. http://bit.ly/JTWearn

      Wearn et al. described the myocardial sinusoids and noted that they connected to the arteriosinusoidal vessels but not to the arterioluminal vessels.

      The vessels of Wearn include the arterioluminal and arteriosinusoidal vessels. Depending on consensus and further study, they may include a variable segment of the myocardial sinusoids.

      Is it possible that some of the VCCs that you describe are not sinusoids but pathologically altered arterioluminal vessels?

      My opinion is that we have probably have insufficient information to definitively conclude in every case whether an arteriosinusoidal or arterioluminal vessel is involved.

      We have discussed these VCCs (VCACs)in relationship to the hypertensive right ventricle of PAIVS. The vessels of Wearn identified in PAIVS is presumably related to the VCCs that you report in the hypertensive left ventricle of MSAA.

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

      The vessels of Wearn connect to both the atria and the ventricles. The vessels of Wearn include the VCC (VCACs) and atrio-coronary-connections (atrio-arterio-cameral connections).

      If the reader is interested in additional commentary related to these connections, please see the following links:

      https://twitter.com/BrettSnodgrass1/status/418829863609331712

      https://twitter.com/BrettSnodgrass1/status/421401527035510784

      https://twitter.com/BrettSnodgrass1/status/420281076070637568

      https://twitter.com/BrettSnodgrass1/status/419599948368183296

      My aim is to help produce accurate medical nomenclature and I proposed the term “vessels of Wearn” for the previously unnamed vessels. http://www.ncbi.nlm.nih.gov/pubmed/22704295

      In summary, please consider that the term sinusoids may not always be related to the VCCs you describe, but the vessels of Wearn is probably applicable (arteriosinusoidal & arterioluminal connections).

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

      Comments and suggestions are welcome.

      Thank you kindly.


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    1. On 2016 Aug 19, Morten Oksvold commented:

      Please note that this article has been retracted and should therefore not be cited in the future.

      http://onlinelibrary.wiley.com/doi/10.1002/ijc.30271/full


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    1. On 2017 Sep 13, Donald Forsdyke commented:

      WHAT IS THEORETICAL BIOLOGY?

      In a 2011 letter to the editor, I wrote in a somewhat too boisterous fashion questioning the Editors-in-Chiefs' statement on the nature of theoretical biology. The advent of PubMed Commons now makes it possible to reproduce my unpublished letter, which quotes from their statement:

      With 23 papers in the JTB stretching from 1969 to 2009, I am perhaps qualified to congratulate the various Editors who have built on the foundation Professor Danielli so carefully laid in 1961. Yet the letter of the present Editors-in-Chief [1], while claiming to "reflect on the history of theoretical biology," notes that in 1961 "theoretical biology was largely in its infancy."

      This will raise many eyebrows – particularly among those of us who have recently celebrated the Darwin Centenary. Apart from Charles Darwin, the many others set rotating in their graves by this remark will include Gregor Mendel, Francis Galton, George Romanes, William Bateson, Herman Muller, JBS Haldane, Theodosius Dobzhansky, McFarlane Burnet and Francis Crick. At a time when "hundreds of our reviewers are women," the disregarding of these past male contributions hints at political correctness.

      That the present Editors also consider this "a field based largely on mathematics" would also have struck many of these giants – even Mendel, Galton and Haldane – as bizarre. Thus to the question: "Whether the focus and content of JTB has changed over these fifty years?" one must suspect increasing tendencies to (1) dismiss the history of our subject, (2) follow political agendas, and (3) depart from verbal analysis to mathematical modeling.

      It will be interesting to see how many of the experts in the field who have been commissioned by the present Editors to provide reviews of its past, present and future, will note what I believe to have been an unfortunate departure from Danielli’s original goals.

      [1] D. Kirschner, Denise Kirschner, Fifty years of JTB: Past, present and future a letter from the editors-in-chief, J. Theor. Biol., (2011) doi:10.1016/j.jtbi.2010.09.004 Kirschner D, 2011


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    1. On 2015 May 14, University of Kansas School of Nursing Journal Club commented:

      Team 12: Effect of a Quality Improvement Intervention on End of Life Care in the ICU Group 12: Stacy Hanson, Jen Huynh, Sami Johnson, Valerie Melin, Shannan Orpin, Chelsi Puskas, Chandler Schoen

      Background: Upon review of this article, our team found many ways that the content within relates to both previous and current discussions in our Nursing in an Evolving Health Care System course. It covers recent class concepts such as quality improvement and previous topics such as creating a healthy work environment and interprofessional collaboration. We chose this article because it relates to many interests and future careers of our fellow peers upon graduation - critical care - and discusses the effect of an intervention that will improve end of life care in the ICU setting. The gap in knowledge that we feel this article attempts to fill is that of how to provide quality end-of-life care and how it affects patient and family mentality when quality of care are both inadequate and exceptional. We are aware that in this specific area of practice, mortality rates are high and studies have shown that quality of the death and dying component of care is far from adequate.

      Methods: As a team we searched, CINAHL, PUBMED & ProQuest Nursing & Allied Health Sources. We attempted to initially find an article using keywords such as “Professional Nursing Organizations” and “Professional Nursing Organizations in the healthcare setting” but we were unable to find adequate articles that other members of our class had not already claimed. We attempted a different approach and began typing keywords into the search engine such as “Quality improvement in the nursing setting” and we stumbled upon this five star research article in ProQuest. In this quantitative study, a multifaceted, interdisciplinary, quality-improvement intervention was developed to assess the quality of the death and dying process among twelve random hospitals. This study was an unblended cluster-randomized trial (Curtis et al., 2011). Other aspects that were assessed were that of family satisfaction levels, the patients length of stay in the Intensive Care Unit, how long the patient was on mechanical ventilation and the delay before removing them from this equipment and nine chart-based palliative care elements (Curtis et al., 2011). The intervention specifically focused on clinicians and assessed how five core components were integrated within their care on a day-to-day basis: “clinician education about palliative care In the ICU using a variety of education approaches, identification and raining of ICU clinician local champions for palliative care, academic detailing of nurse and physician ICU directors to address individual ICU-specific barriers to improving end-of-life-care, feedback of individual ICU-specific quality data including family satisfaction, and implementation of system supports such as palliative care order forms” (Curtis et al., 2011, p. 349). The intervention impacts all of the healthcare staff in the ICU setting, family members/loved ones and ultimately the patient during this tough time. As stated earlier, 12 hospitals were chosen randomly. Of those hospitals, six were unsystematically chosen for the intervention to be implemented, while the other six served as the control group. Patients were eligible if they had passed away in the ICU or within thirty hours upon discharge/transfer. If the patient was in the ICU for less than six hours, they were not eligible for the study (Curtis et al., 2011). Data was collected through questionnaires distributed to both nurses and family members of the deceased patient. The questionnaire, The Quality of Dying and Death (QODD), addressed to the family was sent four to six weeks after, measuring their viewpoints on their loved one’s quality of care received during the death and dying process. It also measured their levels of satisfaction with the care they received during their overall time in the ICU setting. The nurses too received the QODD questionnaire, 72 hours after death evaluating their outlook on the care they provided (Curtis et al., 2011).

      As a team we found this study to hold high importance so that we as healthcare providers can provide care that is of the utmost respect, granting the last wishes of our patients before they pass away. As nurses, it is an honor to care for someone during the death and dying process, and being a support system that the family and patient can lean on in times of need.

      Findings: After the study was implemented and the results were measured, there was no change in the quality of care provided to patients in the ICU setting during the death and dying process. With further research, we identified barriers that may have contributed to this finding. One limitation present throughout this study was the expense and time consumption of randomizing hospitals. Due to this, there was not an adequate sample size to draw appropriate conclusions from, nor equal distribution of patient characteristics. Another constraint found within the study was the complexity of the intervention implemented, making it difficult to measure the success of delivery. This study was also limited to only the United States, making transferability difficult to other regions (Curtis et al., 2011). A few of our team members have experienced the death and dying process internationally upon a service learning experience in Gulu, Uganda, summer of 2014. After reading this article, our team held a unique discussion about quality and quantity of life and the differences in protocols when it comes to dealing with the death and dying process internationally and in the states. Valerie and Stacy discussed their findings, where life-sustaining resources are not available. As a team we talked about how, even though they do not have great technology and resources their quality of life is better because their existence is not prolonged at detrimental costs.

      Implications: This literature that our team selected is important to the nursing practice because it provides us with a new perspective on how the death and dying practice can be improved to make the end of life process more accepting. Through this article, we realize how crucial it is to be able to grant the last wishes of a patient. We realize that as future nurses, death is unavoidable and for many of our career trajectories, we will be faced with this situation often. We use this study to acknowledge how important it is to advocate for family members and patients in the most vulnerable times of their life. This research article brings to light the importance of communication among all professions, the importance of patient centered care, and the importance of how quality improvement projects advance the nursing profession. As stated previously, this concept is important on a personal level, so that we can be more aware and sensitive to how we can help family members cope with one of the most difficult situations one ever has to face.

      As we transition into the new graduate position, it will be crucial that we can identify areas in need of improvement, that we continuously challenge our practice, searching for the best available evidence and protocols out there to provide patient centered, holistic care. We all are committed to our involvement in quality improvement projects as we strive to be the best nurses we can be.

      Reference: Curtis, J. R., Nielsen, E. L., Treece, P. D., Downey, L., Dotolo, D., Shannon, S., Back, A., Rubenfeld G., Engelberg, R. A. (2011). Effect of a quality-improvement intervention on end-of-life care in the intensive care unit: A randomized trial. American Journal of Respiratory and Critical Care Medicine, 183(3), 348-55.


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    1. On 2014 Feb 12, Preben Berthelsen commented:

      This study was registered with ClinicalTrials.gov (NCT00299650). The primary outcome measure was the “Reduction of the mortality rate of ARDS patients at d90”. The result of the investigation was that there was no statistically significant difference between the mortality of patients treated with NMBA or placebo. In the paper, however, the primary outcome measure has been changed to “the adjusted 90-day survival” and this change of the primary outcome measure - from crude to adjusted mortality - results in the statistically significant different mortality rates reported in the paper. In my opinion, we need more compelling and irrefutable valid evidence before we accept that 48 hours of NMBA treatment influences the mortality rate of a complex pathophysiological entity like ARDS. P.G.Berthelsen, MD. Denmark


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    1. On 2013 Nov 24, John Sotos commented:

      The diagnostic evaluation of the post-partum woman with coronary artery dissection in case 28-2010 (1) was inadequately reported.

      I suspect the patient’s cardiac catheterization included aortography, or at least a quick aortic “root shot,” that was not disclosed. Coronary dissection mandates such an evaluation, given its association with simultaneous aortic dissection and with the aortic ectasia seen in heritable disorders of connective tissue (as noted in the case’s table 2). Finding aortic disease would likely have altered this patient’s surgical management.

      More concerning, the patient’s physical examination omitted pertinent negatives related to connective tissue disorders that cause aorto-coronary dissections, e.g. body habitus, joint hypermobility, skin laxity, visual acuity, and, remarkably, the bifid uvula of Loeys- Dietz syndrome (2).

      Aortic diseases have high mortality when untreated (3). They should always be considered when adults, of any age, have chest discomfort, and should remain in the differential diagnosis even after a coronary dissection is found.

      (1) Case records of the Massachusetts General Hospital. Case 28-2010. A 32-year-old woman, 3 weeks post partum, with substernal chest pain. Sabatine MS, Jaffer FA, Staats PN, Stone JR. N Engl J Med. 2010 Sep 16;363(12):1164-73. Pubmed 20843252 doi: 10.1056/NEJMcpc1000966

      (2) Aneurysm syndromes caused by mutations in the TGF-beta receptor. Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, De Backer JF, Oswald GL, Symoens S, Manouvrier S, Roberts AE, Faravelli F, Greco MA, Pyeritz RE, Milewicz DM, Coucke PJ, Cameron DE, Braverman AC, Byers PH, De Paepe AM, Dietz HC. N Engl J Med. 2006 Aug 24;355(8):788-98. Pubmed 16928994

      (3) Hirst AD, Johns VJ, Kime SW. Dissecting aneurysm of the aorta: a review of 505 cases. Medicine 1958;37:217-279. Pubmed 13577293


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    1. 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


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    1. On 2014 Dec 10, Kath Wright commented:

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


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    1. On 2014 Jul 03, Lane Rasberry commented:

      The journal publishing this is providing a copy which is free to read at http://secure.medicalletter.org/w1347c


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    1. On 2013 Nov 05, Yasset Perez-Rivevol commented:

      A new version of the N-terminal software to identified PITC modified peptides can be found in http://www.ncbi.nlm.nih.gov/pubmed/23448308. The software was renamed to HI-Bone.


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    1. On 2015 Oct 05, Lydia Maniatis commented:

      In this publication, as in both older and more recent ones by various authors, "brightness" is being described as as the perceptual correlate of luminance, and is supposed to be interchangeable with lightness when there are no visible illumination boundaries. But as I've noted in comments on Blakeslee and McCourt (2015) and Gilchrist (2015), we can't say that there is a perceptual correlate of luminance, even under (apparently) homogeneous illumination, and this can be proved as follows:

      We ask an observer to report on the lightness of a set of surfaces which don't produce the impression of shadows or transparency. Then, in a second session, we present the same set of surfaces under a different level of illumination. The lightness reports for the surfaces will stay essentially the same, even though their luminances may have changed substantially. So to say that people are making "brightness" judgments - i.e. perceiving luminance - in either the first or the second or in any case doesn't seem to fit the facts.

      In the case of non-homogeneous illumination and double-layers, the position still doesn't make sense, because it implies that we see a surface plus a shadow/transparency, plus a third thing. Is this the case? And how is the value of this third percept supposed to be determined? On the basis of absolute luminance?


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    2. On 2015 Nov 02, Lydia Maniatis commented:

      In this review, Kingdom refers to the “unrelenting controversy” supposedly raging in the study of lightness/brightness/transparency: “Divided into different camps, each with its own preferred stimuli, methodology and theory, the study of LBT is sometimes more reminiscent of the social sciences with its deep ideological divides than it is of the neurosciences.” This quote makes immediately clear that the prevailing controversies reflect, not an intellectually competitive environment, but a highly permissive one of ad hoc hypotheses, each remaining safely within the limits of the stimuli and methodology that will corroborate it, again and again. Beyond these limits, the hypotheses are typically either untestable or easily falsifiable. Yet they remain in good standing for many years, part of the pseudo-controversy, generating endlessly repetitive and poorly-rationalized editorial and experimental publications.

      Kingdom's review is characteristic of this permissive approach. Despite claiming to “critically analyze” theoretical approaches, everyone essentially gets a free pass. One example is described in the asterisked footnote (below). A second example relates to Kingdom's discussion of “edge-integration models.” We learn that Rudd et al have managed to “quantitatively model assimilation, contrast and edge-integration data.” In other words, they have constructed ad hoc accounts of some data. However, while such modeling may be possible for simple stimuli, for “complex two- dimensional images the process is computationally expensive and, one cannot help feel, physiologically implausible.” But the researchers are “keenly aware of this limitation” and anticipate improving their model to, perhaps, attain plausibility.

      Of course, there is nothing wrong with working hard to validly articulate and test a hunch. But until it is testable and tested, it cannot be considered a competitor in good standing. The prevailing standard of “partial success” is a standard of failure. Controversy among proposals that are half-baked, untestable and/or fail as soon as they leave their comfort zone is of marginal scientific interest.

      • An example that I am particularly familiar with is the “anchoring theory.” I recently published a “simple test” of fundamental claims/assumptions of this construct – and it failed. The test was easy to conceive – trivial, actually - and the outcome highly predictable. I learned after the fact that at least one other investigator had, a while back, considered publishing something to the same effect. Despite this clear falsification of fundamental (if vague) assumptions (as well as previous falsifications), the failed “anchoring theory” is continuing to chalk up “successes.”


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    1. 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 NCT0100468. We believe the correct ID, which we have found by hand searching, is NCT01004068.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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


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    1. On 2014 Sep 29, John Friesen commented:

      This well designed study demonstrates two important things about induction doses of propofol in morbidly obese patients. First, they are best normalized to the lean body weight. Second, the dose required is affected by the rate at which it is administered.

      The authors recommend using the lean body weight to estimate the dose for morbidly obese patients. However, any clinically useful weight scalar must be equal to the total body weight for patients of normal weight. Because the lean body weight is always less than the total body weight even for non-obese patients, it cannot be used directly to calculate doses drug doses: it will result in underestimation, and must be scaled upwards(1).

      For example: a woman weighing 105 kilograms with a height of 170 centimeters and a BMI of 36.3 presents for bariatric surgery. Her induction dose of propofol is based on her calculated lean body weight5 of 55.2 kilograms. She successfully loses weight, and she returns for another operation having lost 40 kilograms. She is no longer obese, and her induction dose is based on her total body weight of 65 kilograms. Assuming that she is given 2.0 mg/kg of propofol each time, her calculated dose is 110 mg when she weighs 105 kilograms, and 130 mg (20 mg more) when she weighs only 65 kilograms. This is not correct.

      The lean-scaled weight is a weight scalar that is proportional to the lean body weight for all obese and non-obese patients(2). It is calculated by multiplying the lean body weight function(3) by a normalization factor such that it is equal to the total body weight at a BMI of 22. This factor is 1.2332 for men and 1.5262 for women: for the 105 kilogram woman in the example, the lean-scaled weight is 84.2 kilograms.

      It is interesting to ask what results might have been obtained if this study had included a morbidly obese group administered propofol at a rate proportional to the lean-scaled weight. Combining the two morbidly obese groups the mean total body weight is 131.1 kg and the lean body weight is 67.05 kg. For a BMI of 46.55, the mean lean-scaled weight (given the proportion of males to females) calculates to be 91.09 kg for this imagined group. Using these values to interpolate between the results reported for the infusion rates used in the study, the dose estimated to a linear approximation is about 2.27 mg/kg of lean-scaled weight.

      The lean-scaled weight is equal to the total body weight for non-obese patients, and therefore this result can be compared directly to the 2.57 mg/kg reported for the control group. 2.27 mg/kg is close to this value, and well within the reported error. The results of this study are consistent with using the lean-scaled weight when estimating induction doses of propofol, for both obese and non-obese patients.

      References

      1 Bouillon T, Shafer SL. Does size matter? Anesthesiology. 1998 Sep;89(3):557-60.

      2 Friesen JH. Lean-scaled weight: a proposed weight scalar to calculate drug doses for obese patients. Can J Anesth. 2013 Feb;60(2):214-5.

      3 Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green B. Quantification of lean bodyweight. Clin Pharmacokinet. 2005;44(10):1051-65.


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    1. On 2015 Apr 13, Mark Wewers commented:

      Consider our report Kannan Y, 2011 which showed the NFKBIZ association with interferon gamma in human cells but is not being appropriately indexed as NFKBIZ paper by MESH headings.


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    1. On 2014 Oct 15, Amanda Capes-Davis commented:

      Please be careful to view the erratum here if working with hTERT-EEC cells. As shown by Korch et al 2012 (PMID 22710073), hTERT-EEC is known to be misidentified and is actually MCF-7. So cells are from breast carcinoma, not immortalized endometrium.

      Authentic stocks are always a possibility, so labs are encouraged to test their stocks using a consensus technique such as STR profiling. For a list of known misidentified cell lines, see http://iclac.org/databases/cross-contaminations/.


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    1. On 2013 Nov 01, Hilda Bastian commented:

      Our estimation of "11 systematic reviews a day" is out of date. There has been a striking increase in systematic reviews since that original analysis (ending with data from 2007). In August 2013 Paul Glasziou and I updated the data in Figure 3 estimating the number of systematic reviews, including data up to 2012.

      The update showed that by 2012, there were around 26 systematic reviews a day. The updated figure is available here. Addressing the challenges we identified in keeping up with the evidence have thus become more critical.

      (We are grateful to Claire Allen at the Cochrane Collaboration for providing the data on the number of Cochrane reviews.)


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    2. On 2013 Nov 12, Paulo Rossetti commented:

      The way to communicate science for general clinics is a complicated issue. Meta-analysis could be a two-page article only with what is extremely necessary for clinics. Maybe, some people can design a self-explained forest plot similar to what we have now for some themes with smartphone technologies.


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    3. On 2016 Sep 16, Hilda Bastian commented:

      I have posted updated data on key charts here. The data are updated to 2013 for the charts with systematic reviews and 2014 for trials.

      If you are interested in this topic, the Page MJ, 2016 paper is a must read. We relied in large part on filters to chart trends: Page and colleagues rigorously studied a month's worth of systematic reviews from 2014.

      Disclosure: I work on projects related to systematic reviews at the NCBI (National Center for Biotechnology Information, U.S. National Library of Medicine), including some aspects that relate to the inclusion of systematic reviews in PubMed.


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    1. On 2014 Feb 15, Amanda Capes-Davis commented:

      Unfortunately this work has not been done using intestinal epithelial cells. INT-407 is known to be cross-contaminated by HeLa and is actually cervical adenocarcinoma. For a full list of known cross-contaminated cell lines, see http://iclac.org/databases/cross-contaminations/.


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    1. On 2015 Jun 08, Prof.Dr.Jogenananda Pramanik commented:

      Invited co-authors: Dr.Cao Yulin MD.PhD CEO, International Centre for Biogenetics and Stem Cell Research ( ICBSCR), Beijing; Dr.Juntang Lin, Research Group Leader, Jena University, Jena, Germany.

      Despite rigorous internal and external quality control measures and close supervision from China Academy of Sciences and related Governmental regulatory agencies, we humbly accept that certain limitations and risk factors that are existing in stem cell therapeutic procedures in China like any other developed countries. However, we are painfully conscious to observe the organized efforts to hinder the flow of patients from western world to different hospitals in China seeking stem cell therapy for different disorders. Since past few years stem cell therapy is picking up tremendous popularity among patients recovering from incurable diseases like cerebral palsy, IDDM and others. Amidst several restrictions, stem cell therapy is practised in India, Malaysia and other South East Asian countries. Governmental regulatory bodies are sincerely employing necessary regulations where ever required and therefore their efforts are commendable in view of the safety of our patients. As all of us understand that virtually no medical treatment is without risk and so is for cell-based therapy in general. However, as stem cell research progresses and legitimate medical innovation using stem call-based applications become more of a reality, all those issues will hopefully be settled step by step. We in no way wish to place any blame on individuals who are determined to pursue hope in what are often extremely difficult and discouraging circumstances (1 & 2). References: 1.Editorial:Stem-cell laws in China fall short: Nature;467,633(07 October 2010/ doi.10.1038/467633a. 2.Jogenananda Pramanik & Tanu Pramanik: Stem Cell Therapy Controversial? Re: Netherlands bans stem cell therapy:BMJ2007;334doi.http;//dx.doi.org/10.1136/bmj.39072458449.DB(Published 04 January 2007)


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    1. On 2014 Mar 12, Johnson Francis commented:

      Any other recent trials on MRI conditional pacemakers?


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    1. On 2013 Oct 29, Tom Kindlon commented:

      Was this study sufficiently powered to find oxidative phosphorylation?

      It is not desirable if a promising line of enquiry is prematurely ended by an underpowered study. Looking at Table 4 and in particular, rows 1, 2 and 4 where the figures go up for the controls from test 1 to test 2 and go down for the CFS/ME patients, I am left wondering whether a bigger study would have found a statistically significant difference. This is not a criticism of the researchers as, like all teams, I'm sure they would have preferred bigger samples but funding and other issues restrict what is possible for any one study. Also, the team in this case probably did not have advance data to do power calculations. It will be interesting to see if similar changes are evident in future studies* and whether pooled data would show differences even if individual studies don't reach the magical "statistical significance".

      *if any researchers investigate this again - the volume of study in CFS is low and there is a range of issues to look at


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    1. On 2015 Mar 25, University of Kansas School of Nursing Journal Club commented:

      Team 10: Jenny Allin, Lauren Andrus, Morgan Cross, Stephanie Gass, Joey Leoni, Jamie Lockwood, Ryan Rogers, Malorie Schuler

      Upon near completion of nursing school, our class has discussed numerous topics pertaining to leadership, change agency, and collaboration, or shared governance. Our group selected this article because it encompasses the true importance of collaboration between professions, as well as displaying the true impact that nurses can have on the overall work environment and structure. Thus far we have discovered many opportunities that we will have as future nurses to become an active member in our organization. In one instance, we may become part of committees in order to give a voice to the nursing profession during in major policy changes or decision-making processes. The selected article displays the ways in which the interwoven relationship between transformational leadership and shared governance can result in a successful and motivating work environment. Additionally, we found this article to answer the question as to whether or not nurses can both impact change and promote advancements in the overall structure, while also feeling more empowered and self-confident with such involvement.

      The information from this descriptive and exploratory study, found by means of the CINAHL database, was obtained from personal reflective practices and self-reporting. The creators of the study collected the data by speaking with nurses involved in transformational leadership and the impact shared governance has on their unit and patient care as a whole. In order to acquire relevant articles to the topic we wished to review the following keywords were used: shared governance, nursing, and leadership. Our group feels the population targeted by the authors are nurses that lack confidence and motivation that their involvement in shared governance committees and processes. The nurses identified in the study do not yet realize that their input can and will make a positive impact on their peers as well as their patients. We also feel that members from various other healthcare professions could have been targeted in this study, albeit secondarily. It would be beneficial for other team members to review this study and discover the contributions nursing can make if given the respect and opportunity to do so.

      Overall, this study reinforced the fact that shared governance when paired with transformational leadership, results in a profession that can “function effectively in a contemporary healthcare environment” (Bamford-Wade & Moss, 2010, p.819). When a unit or structure provides these opportunities for their employees, those employees are then filled with a greater sense of worth, self-esteem, autonomy, and responsibility (Bamford-Wade & Moss, 2010). Although this study was conducted and completed in New Zealand, the findings were consistent with that of research attained through studies in the United States. It is interesting to see the particular successes in healthcare translate to numerous locations and cultures around the world. While our group felt this article was reliable as well as valid, we would have liked to see more concrete data and statistics related to the impact of shared governance. Self-reporting and reflections are advantageous because they disclose information that numerical figures cannot, however, specific quantitative data may have made the study much stronger.

      Information on transformational leadership and shared governance is imperative to professionals in the nursing practice. It encourages nurses to be aware of the opportunities they have available in order to become an agent of change in his or her organization. These two topics are not absolutely understood, and therefore are often overlooked or ignored by many registered nurses that have the capacity to make an incredible difference. As new graduates, it will be easy to forget these opportunities and to believe that our voices will not be heard. Our group discussed that reviewing articles and examining research that cover these topics reminds us that our profession does not simply consist of completing tasks and charting. Rather, personal and individualized patient care, safety, and beneficial work environments are essential components to our career as well, and who better to advocate for nurses than themselves? We enjoyed this article because it coincided with the information from through several of our previous BSN courses, and made us feel empowered to become leaders and members of shared governance teams in the future. While leadership may initially begin at the unit level, RN contributions can expand through the different chains of command and result in a facility-wide change in patient care.


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    1. On 2013 Oct 24, Leonard Foster commented:

      The spectra used to identify IIV peptides in this study actually match much better to honey bee peptides, which were not included in the protein database used here. For more information see:

      Tokarz R, 2011 Knudsen GM, 2011 Foster LJ, 2012 Foster LJ, 2011


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    1. 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


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    1. On 2015 Jul 18, Jan Tunér commented:

      This study used 90 J/cm2, a very high dose, and because it was achieved by using a 15 W, 980 nm laser for 3 sec per cm2 and increasing the skin temperature up to maximum 50 degrees, it is obvious that this is not LLLT as we know it, and of course it is not effective. Traditional doses for wound healing are around 4 J/cm2 and low power and long time is more effective than high power and short time, even when applying the same energy. Reference: Castano A P, Dai T, Yaroslavsky I, Cohen R, Apruzzese W A, Smotrich M H, Hamblin M R. Low-level laser therapy for zymosan-induced arthritis in rats: Importance of illumination time. Lasers Surg Med. 2007; 39 (6): 543-550.


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    2. On 2015 Aug 06, Serge R Mordon commented:

      we thank Jan Tuner for having commented our article published 5 years ago. We confirm that we conducted a prospective comparative clinical trial aimed at evaluating 980 nm diode laser in laser-assisted venous ulcer healing. Laser parameters were chosen to generate a local temperature of 45-50 °C, which was controlled with a thermal infrared camera. Our study has nothing to do with LLLT. It would be very interesting to evaluate LLLT with the protocol used in our study before stating that LLLT is more effective on venous ulcer.


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    1. On 2016 Feb 16, Gary Goldman commented:

      The Moro et al study concluded that influenza vaccine was safe during pregnancy. This study motivated the March of Dimes, backed by 10 healthcare sponsors (including the CDC), to send a statement of safety associated with the influenza vaccine to all obstetricians prior to the 2009/2010 two-dose (pandemic and seasonal) influenza season, based on (1) the few collected VAERS case reports for the past 20 years through the 2008/2009 influenza season, and (2) failed to account for underreporting to the VAERS database. However, the study authors were aware of an unusually large spike in the number of fetal deaths reports for the 2009/2010 pandemic influenza season (which was not included in the publication).

      A hypothesis for the large spike in the number of fetal deaths among pregnant women receiving the two-dose protocol and a capture-recapture estimate of the true incidence of fetal deaths is presented in the Goldman study published in Hum Exp Toxicol 2013 May;32(5):464-75. Goldman GS, 2013

      Further, a toxicological study using a different methodology came to a similar conclusion as Goldman GS. This study can be found in the archives of Toxicological & Environmental Chemistry as follows: Brown IA, Austin DW. 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 Abstract: Mercury (Hg) exposure is ubiquitous in modern society via vaccines, fish/crustacea, dental amalgam, food, water, and the atmosphere. This article examines Hg exposure in the context of primary exposure to pregnant women and secondary exposure experienced by their unborn babies. Babies in utero are particularly at risk of higher Hg exposure than adults (on a dose/weight basis through maternal Hg transfer via the placenta), and are more susceptible to adverse effects from mercury and its biologically active compounds. 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.


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    1. On 2013 Oct 31, John Cannell commented:

      The authors found markers oxidative stress is 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 the Ameri


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    1. On 2013 Dec 30, Scott Federhen commented:

      CCTCC AA 208081 was designated as the type strain of both Pseudonocardia artemisiae Zhao GZ, 2011 and Pseudonocardia kunmingensis Zhao GZ, 2011. The corresponding author (Wen-Jun Li) has confirmed that this is the article with the incorrect culture collection accession. The type strain of Pseudonocardia kunmingensis is actually CCTCC AA 208078.


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    1. On 2015 Feb 08, Arnaud Chiolero MD PhD commented:

      A fantastic paper to understand why screening of most cardiovascular risk factors are not performant for the prevention of CVD


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    1. 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 NCT00297150. We believe the correct ID, which we have found by hand searching, is NCT00397150.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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


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    1. On 2013 Jun 18, Wolfgang Huber commented:

      This paper lays out the main ideas behind the DESeq method, which can be used to detect differential abundance in count-based biological data such as obtained from RNA-Seq, ChIP-Seq, HiC, mass spectrometry. In the meanwhile, the method has evolved substantiallly, new features include:

      • treatment of general NB-GLMs (generalised linear models of the Negative Binomial family) including paired designs and interactions
      • better dispersion estimation (especially in the important small sample size setting)
      • outlier detection
      • specialised tools to detect differential relative exon usage, described in Anders S, 2012 and provided by the DEXSeq package on Bioconductor

      For more details on these improvements, see the vignette of the DESeq2 package http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html (which is in the process of replacing the previous implementation, DESeq) and also the Supplement of Anders S, 2012.

      In addition, much practical information is available in online fora and mailing list, in particular https://stat.ethz.ch/mailman/listinfo/bioconductor and http://seqanswers.com/forums/forumdisplay.php?f=18. Generic search engines seem to be a good way to search through these.

      This approach was developed particularly for experiments with limited numbers of replicates. For larger data sets (e.g. observational studies involving hundreds of samples), the granularity of the counts becomes less important and estimating the variability becomes easier, so that also other, more generic methods become sufficiently performant. In particular, data transformations, such as DESeq2's varianceStabilizingTransformation and rlogTransformation, together with general-purpose dimension reduction, clustering or classification algorithms, or with normal ANOVA in these cases often provide attractive options.


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    2. On 2013 Jun 22, Robert Tibshirani commented:

      DESeq represents a promising approach for detecting differential abundance in RNA-seq and other count-based biological data. However it is a parametric method, and my student Jun Li found that as a result, it can be very non-robust to outlying points. The same is true of EdgeR, another well-known method, that like DESeq, uses the negative binomial distribution. And such outlying points can be common in this kind of data--- there are often some extremely large counts.

      Jun and I developed a resampling-based non-parametric method called "SamSeq" http://www.ncbi.nlm.nih.gov/pubmed/22127579 which in our experiments, showed considerably better robustness, with little loss of power when there were no outliers. This method is implemented in the R package "samr" http://cran.r-project.org/web/packages/samr/index.html and in the Excel add-on package SAM http://www-stat.stanford.edu/~tibs/SAM/. Our comparisons were made with the original DESeq method: the new outlier detection features added in DESeq2 might help matters. We haven't tried this comparison and it would be important to do this. A word of caution: I have written only a few papers on this topic, and have not kept up with the latest developments.


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    3. On 2013 Jul 02, Wolfgang Huber commented:

      Robert Tibshirani raises an important point: how does the method react to outliers, e.g. to cases where a gene hovers around the same value for most samples but has extremely different values for a few isolated samples. In some cases, such genes might be of interest, but in most biological applications, users seem to be more interested in genes that show a consistent shift in expression for all or most samples in a condition.

      We have recently adapted DESeq2 to be able to flag (and ignore) such outliers, see Appendix F of the packages vignette, which is available from http://www.bioconductor.org.

      Regarding SamSeq (or related methods), these are very promising in large-sample situations. Section 3.3 of the SamSeq paper Li J, 2013 is titled "Data with small sample size" and considers a comparison of 5 versus 5 samples. However, sample sizes in some applications of RNA-Seq are smaller, controlled experiments with 2 versus 2 samples are not uncommmon. They can be reasonably analysed with parametric methods such as DESeq/DESeq2, and requiring a 250%-fold experimental effort in order to be able to apply a non-parametric method could be uneconomic.

      There is a pressing need for benchmarks; A few years ago, Rafael Irizarry's AffyComp Irizarry RA, 2006 was an excellent example of how to do this, at the time, on Affymetrix arrays applied to designed experiments. It would be interesting to see similar benchmarks for RNA-Seq data, for various experimental or study designs.


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    4. On 2013 Nov 11, James Hadfield commented:

      This paper describes the DESeq method, for differential RNA-Seq, ChIP-Seq and other analyses. DEseq was developed to work on low replicate numbers and indeed many people cannot generate high numbers of replicates. But I would challenge the community to consider that the costs of NGS have dropped very significantly since these methods were conceived and that increasing replicate numbers to higher levels is now inexcusable in many scenarios.

      Both of the papers referred to in the comments so far reference multiple RNA-seq, and/or other, datasets that were used to test the methods from which their conclusions are drawn. Wolfgang Huber mentions the constraints of samples-size in his comments and also has a section on working without replicates in the Anders/Huber paper above, in it they discuss the impact that within and between group sample variability have on the results.

      Some very real difficulties in appraising which approach (DESeq2 or SamSeq) is best include the limited amount of time the community has been testing the different approaches, that the approaches themselves are still very much in development, and that very different datasets are used in each study.

      This last issue is made more of a problem since the experimental methods section in many NGS papers is generally not clear enough. It would help to have clear guidelines on the number samples used and their relationship e.g. biological or technical replicates, and if technical at which stage is replication being made; the number and type of reads generated at a per sample and per group level would also be useful. Getting this information can be painful as evidenced by digging through the DESeq2 and SamSeq references:

      DESeq2

      Wilczynski: very difficult to determine from the data provided or online. Engstrom: mRNATag-seq, 5 samples (3 & 2 replicates per group), no indication of reads per sample.

      Nagalakshmi: mRNA-seq, 4 samples (2 technical & 2 biological replicates per group), 7M reads per sample (possibly).

      Kasowski: ChIP-seq, 10 biological samples, 2 groups, 660M reads 33M reads per sample.

      SamSeq

      Hoen: mRNA-seq, 4 replicates each of around 2.5M reads.

      Marioni: mRNA-seq, 2 groups (liver & kidney), 7 technical replicates (at the lane level), 85M reads per group, 12M reads per replicate.

      Witten: miRNA RNA-seq, 29 biological samples per group (Tumour vs normal), average 0.75M reads per sample.

      Perhaps a simple format could be agreed on by the community as a table to be added in to each publication as a supplemental?


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    5. On 2016 Jan 30, Wolfgang Huber commented:

      The method is superseded by our more recent work: Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Love MI, Huber W, Anders S. Genome Biology 2014 15:550. Love MI, 2014


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    1. On 2016 Aug 17, Enrique de-Madaria commented:

      This case report was written by my grandfather José de Madaria in Spanish, in a local medical journal from Alicante, Spain in 1946, it´s amazing it has been detected by pubmed!


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    1. On 2013 Nov 05, Pedro Mendes commented:

      This describes an improvement of the reconstruction described in Herrgård MJ, 2008. The network reconstruction has since been further improved by Heavner BD, 2012 and Heavner BD, 2013. The up to date data set is available from http://yeast.sf.net/.


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    1. On 2017 May 23, Morten Oksvold commented:

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

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

      http://www.jbc.org/content/286/5/3540.full.pdf?sid=f7ba5ea4-ce35-4a91-b162-ae33702ada92

      "This article has been withdrawn by the authors. The authors were recently made aware of issues in Figs. 2A and 7A as well as supplemental Fig. S4. The 4-hEEE-PEDF panel was reused in the 10n M EEE-PEDF panel in Fig. 2A. In Fig. 7A, the control panel for BAEC cells was reused in the SP600125 panel from BAEC cells in the presence of bFGF and EEE-PEDF. Lane 7 of the pAKT panel from BAEC cells was inappropriately manipulated in supplemental Fig S4. In the interest of maintaining accuracy in the published scientific literature, the authors wish to withdraw this article. However, the authors have full confidence in the findings and conclusions of this paper and have replicated the findings in subsequent work."


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    1. On 2016 May 10, Morten Oksvold commented:

      Please pay attention to the following report by ORI (Office of Research Integrity) before reading this article:

      https://ori.hhs.gov/content/case-summary-pastorino-john-g


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    1. On 2015 Nov 12, University of Kansas School of Nursing Journal Club commented:

      Reviewers (Team 11): Caitlin Colston, April Urie, Bethany Macchi, Lauren Meyers, Madison Steele, Elizabeth Diaz, & Huntre Graham (Senior Nursing Students - Class of 2016)

      Background Introduction:

      Throughout Section 2 in our Microsystem Leadership course, several of the lectures have touched on how crucial it is to have effective leadership in healthcare in order to maintain a trusting and healthy work environment not only for the patients, but for the staff as well. One topic that was recently discussed in class was about authentic leadership and how it can be utilized as an impactful leadership method. The article Authentic Leadership and Nurses' Voice Behaviour and Perceptions of Care Quality further discusses this topic by describing how personal and social identification, trust in the manager, and work engagement are all impacted by an authentic leadership style. The objective of this article is to examine how the authentic leadership style influences the level of trust staff nurses have in their managers, their voice (or speaking up) behavior, and how they perceive the quality of care given on their units (Wong, Laschinger, & Cummings, 2010, p.890). As a group we found that this article helped to clarify at a deeper level how authentic leadership makes a difference in the work environment and should be considered when we participate in future leadership roles.

      Methods:

              “Authentic leadership” and “nursing” were the keywords used when searching the PubMed database for relevant articles. Using this method, our group located several articles to choose from that referred to the topic of authentic leadership in the healthcare setting. After reviewing the relevant articles, we found the article by Wong, Laschinger, and Cummings to be better suited to our topic and research requirements.
             In this study a non-experimental, predictive survey design was used to try to link authentic leadership with staff nurses’ use of voice behavior and their perceptions of the quality of care given (Wong, Laschinger, & Cummings, 2010, p. 892). For the study, the survey was broken down into sections to better ensure accurate depictions of the participant’s thoughts about their work environments. In total there were 6 sections that reviewed authentic leadership, trust in manager, personal and social identification, work engagement, voice behavior, and perceptions of unit care quality. A numerical scale was provided for the participant to rate their answers for each topic. With ethical approval from the University of Western Ontario Ethics Review Board for Health Sciences Research, a sample of 600 registered nurses working in acute care teaching and community hospitals throughout Ontario were randomly selected from the College of Nurses registry list and asked to participate in the study (Wong, Laschinger, & Cummings, 2010, p.892). In order to ensure proper data collection, multiple steps were utilized. The first step of the data collection was to mail the surveys to these nurses with a letter of information describing the study, a stamped return envelope, and a $2.00 ‘thank you’ coffee voucher. A reminder letter was then sent out two weeks after the initial survey mailing and if by three weeks there was no response, a final reminder letter and replacement questionnaire was sent out. Of the 600 requests mailed, there was a 48% response rate resulting in 280 useable surveys received from both full-time and part-time registered nurses for the study. For this study to be successful, it was crucial to ask staff nurses since they are directly impacted by various leadership styles. By gathering this information, the researchers had the potential to not only determine how effective authentic leadership is in the healthcare setting, but they were also able to provide an opportunity for the staff nurses to give voice to their opinions.
      

      Findings:

      The results of the study indicated that staff nurses found their managers to be moderately authentic in the working environment. When describing voice behavior and perceptions of the quality of care given on their units, staff nurses provided a moderately high rating. The participants also reported a moderate rating when discussing trust in their managers and work engagement. Upon review of the overall resulting data, Wong, Laschinger, & Cummings (2010) concluded that, “Authentic leadership significantly and positively influenced staff nurses’ trust in their managers and work engagement which in turn predicted voice behavior and perceived unit care quality” (p. 899). One of the limitations of this study, however, was the use of a cross-sectional design instead of a longitudinal design, which could have offered new information on how managerial use of authentic leadership impacts the work environment of the staff nurses. Another limitation was incorporating the Authentic Leadership Questionaire (ALQ) when discussing authentic leadership in the survey. At the time of the study, the ALQ was not used in nursing samples for other studies, which resulted in the researchers having to compare the some of their data to studies in other fields. Conducting the study in Ontario, Canada could also be considered a limitation as well because though the United States neighbors Canada in close proximity, there was still be a chance of cultural differences affecting the perceptions of the qualitative research provided.

      Implications:

      This article is important to nursing and nursing practice because it provides a foundation of evidence for nursing managers to build their leadership style. When using the authentic leadership style, nurse leaders are able to create a trustworthy environment with the staff nurses, which will then enable the staff to implement safe nursing practices such as voice (or speaking up) behavior. As students of KU School of Nursing, we are consistently told that we all have the potential to become leaders in the future, yet many of us are intimidated by this idea. By reviewing this piece of literature we can begin to visualize ourselves as effective leaders utilizing the most appropriate leadership styles; it is only in this way that we can meaningfully impact the healthcare setting by building positive relationships with our supervisors, peers, and staff.

      References

      Wong, C. A., Laschinger, H. K., & Cummings, G. G. (2010). Authentic leadership and nurses' voice behaviour and perceptions of care quality. Journal of Nursing Management, 18(8), 889-900.


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    2. On 2015 Nov 13, Lydia Maniatis commented:

      I would like to note that the title of this article is rather unclear ("nurses' voice behaviour...?).


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    3. On 2015 Nov 16, University of Kansas School of Nursing Journal Club commented:

      "Voice behaviour" in this article is synonymous with "speaking up" and getting nurses involved in a meaningful conversation, addressing safety issues on the unit which our students have been exposed to through their TeamSTEPPS training in school.


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    1. On 2014 Dec 10, Kath Wright commented:

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


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    1. On 2016 Jun 03, Ian Fingerman commented:

      The Epigenomics database, a public repository that was developed to archive genome-wide maps of DNA and histone modifications, will be retired on June 1, 2016.

      All epigenomics data are available in our GEO resource. If you are specifically interested in the NIH Roadmap Epigenomics Project, we will maintain a page for this project's data.


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    1. On 2013 Oct 24, Jeff Kiefer commented:

      This is a great tool for analyzing one's gene set enrichment analysis (GSEA) results (http://www.broadinstitute.org/gsea/index.jsp). The output of a GSEA analysis is a ranked list of gene sets. The end-user is often at a loss in summarizing and interpreting the output. This is due to the redundant nature of gene sets and often less than useful names of the gene sets. The enrichment map (http://baderlab.org/Software/EnrichmentMap/) is just the tool to resolve the redundancy and assist in interpreting the biological meaning of the GSEA table of gene sets. The tool is relatively easy to use and has decent use case examples and user manual. In addition, a 'methods' paper for the use of Enrichment Map is published here Merico D, 2011. The authors also have an additional tool, WordCloud Oesper L, 2011 that assists in summarizing groups of gene sets visualized using the Enrichment Map. This helps the user to assign textual descriptions and aids in summarizing the represented biology. The WordCloud tool can be found here: http://baderlab.org/Software/WordCloudPlugin. I highly recommend these tools for interpreting GSEA results.


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    1. On 2017 Jan 23, Christopher Southan commented:

      IUPHAR-DB is now subsumed into a new resource. For the latest description see "The IUPHAR/BPS Guide to PHARMACOLOGY in 2016" https://www.ncbi.nlm.nih.gov/pubmed/26464438


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    1. On 2013 Oct 29, Tom Kindlon commented:

      The authors say, "As this was a proof of concept study; physical activity was not formally assessed. Biochemical markers including plasma polyphenol levels and inflammatory markers were not measured as part of the study as all of the baseline parameters prior to the study were normal, in accord with the criteria for the diagnosis of chronic fatigue syndrome."

      The authors are presumably referring to the fact that the Fukuda definition<sup>1</sup> requires researchers to exclude patients with medical or psychiatric disorders that could explain the chronic fatigue and other symptoms. However it is not the case that no abnormalities will ever be found in CFS (plenty have been) nor that the definition encourages researchers not to track biological markers.

      Reference:

      [1] 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(12):953-959.


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    2. On 2013 Dec 18, Tom Kindlon commented:

      Chalder Fatigue Scale scores: there appear to be at least two errors, possibly more

      There appears to be at least two errors in the abstract which are repeating errors from Table 3. The median must be within the range.

      So the following two results are impossible: "deteriorated significantly when subjects were given simulated iso-calorific chocolate (CLF/CP) [ 28.5 (17 - 20)vs. 34.5 (13-26)".

      There may be other errors but I cannot be 100% sure. There are two versions of the Chalder Fatigue Scale: the original 14-question version and the version that is more widely used in CFS research now, the 11-question version. The authors appear to be using the 11-question version as they say "Subjects having severe fatigue of at least 10 out of 11 on the Chalder Fatigue Scale (binary scored) were enrolled [11]." They also say they are using the likert version. For the 11-question version, the range of possible scores is 0-33. However there are values given greater than 33 in the abstract (which is taken from Table 3) e.g. 34.5, 35 and 38.

      If the authors could post the correct information and reply to the point(s) in paragraph 2, it would be appreciated.


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

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


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    1. On 2013 Jul 11, Joshua L Cherry commented:

      This article presents an analysis of glycosylation patterns and sequence variations among human H1N1 influenza virus hemagglutinins. The authors conclude that glycosylation decreases sequence variation at nearby positions in the linear sequence by modifying selective pressures, perhaps by shielding these residues from antibodies. Careful examination of the results, especially with a phylogenetic tree in hand, shows that this conclusion is unfounded. The "extra" sequence variation observed among those viruses lacking glycosylation in a region did not arise among viruses lacking glycosylation in that region. Rather, this variation is the result of the mutations that eliminated the glycosylation site.

      A clear example is the peak of variation at position 129 in Fig. 3 for the {91, 162} class. Sequences glycosylated at position 129 necessarily have an asparagine at this position, and hence no variation. For this reason alone, the high variability compared to sequences with glycosylation in region 129 is a trivial result. Furthermore, mapping of the sequence changes onto a phylogenetic tree shows that the sequences in class {91, 162} (which contains 2% of the sequences) are derived from class {91, 129, 162} (the largest class, with 68% of the sequences) by loss of a glycosylation site. All of the variation at position 129 appears to be the result of mutation of the asparagine in a 129-glycosylated virus that eliminates the glycosylation site, moving the sequence into class {91, 162}.

      The nearby peak at 131 has a similar explanation. This site must be S or T for glycosylation at 129, so its mutation leads to loss of that glycosylation site. Also, some of the glycosylation sites in the 129 region are at position 131, and mutation of that asparagine is another way for a sequence to move into the {91, 162} category. All of the variation at position 131 appears to have arisen in one or the other of these ways.

      The peaks at 164 and 166 for the {91, 129} class have an analogous explanation. The remaining claimed examples of the phenomenon are attributable to the same effect combined with problems with residue numbering due to the treatment of partial sequences, alignment gaps, and ambiguity characters.

      Thus, the observed peaks represent losses of glycosylation rather than changes to unglycosylated sequences. These mutations may have been selected by growth in the laboratory; loss of glycosylation sites is a common laboratory adaptation. Even if the variation is natural, it is not evidence of the claimed phenomenon.

      Some comments are also in order about the comparisons in Fig. 4. First, the positions of the most prominent variation outside of glycosylation regions, around position 190, are know sites of laboratory adaptation. Thus, the peaks are likely artifactual. Second, some of the comparisons involve categories that have different representations of regions of the sequence, and hence are not comparable, and the statistical tests appear to take no account of the lack of phylogenetic independence.

      It is reasonable to think that glycosylation affects selection pressures at nearby residues, and to search for evidence of this in the protein sequences. Such a search should probably begin with mapping the mutations to a phylogenetic tree.


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    1. On 2013 Oct 22, DAVID SANDERS commented:

      None


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    2. On 2013 Oct 23, Pedro Mendes commented:

      Apart from the many comments that have appeared in the journal Science (listed above), Basturea GN, 2012 is also relevant in this discussion.


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    3. On 2013 Oct 25, DAVID SANDERS commented:

      It has been argued that this article should be retracted on the basis of analysis of the statistical data presented in it.

      http://retractionwatch.wordpress.com/2012/07/09/despite-refutation-science-arsenic-life-paper-deserves-retraction-scientist-argues

      http://www.periodicplayground.com/blog/bp/2013/02/guest-post-david-sanders-why-its-high-time-to-retract-arseniclife


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    1. 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


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    1. On 2016 Nov 18, Morten Oksvold commented:

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

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

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

      This article should therefore no longer be cited.


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    1. On 2014 Jan 11, Brett Snodgrass commented:

      Dear Authors,

      Thank you for publishing an excellent article.

      Might the precapillary (and possibly capillary) sinuses you reported be related to the "myocardial sinusoids" described by Joseph Treolar Wearn?

      http://bit.ly/JTWearn

      Comments and suggestions are welcome.

      Thank you kindly.


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    1. On 2018 Jan 31, Denise N Slenter commented:

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


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    1. On 2013 Oct 29, DAVID SANDERS commented:

      From Lynch CM, 1992 "Nabel et al. have reported direct gene transfer into quiescent cells in all layers of the arterial wall of Yucatan minipigs by both retroviral infection and by lipofection using B-gal as the marker gene. High levels of background B-gal activity resulting in false positives were not reported. However, given that blue staining of vessels exposed to virus was the only criteria used to document gene transfer, and given the variable background staining that we and others Lim CS, 1991 observe, these results must be confirmed by additional molecular analysis to verify the presence of the vector. If gene transfer did occur under these conditions,we predict that the efficiency of gene transfer must have been very low..." See also Flugelman MY, 1992.


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    1. On 2014 Jan 08, Tom Kindlon commented:

      "SF-36 physical function" should read "SF-36 PCS" I believe

      There are 8 SF-36 subscales: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social functioning, Role-Emotional and Mental Health. There are also two composite scores: Physical Composite Score (PCS) and Mental Composite Score (MCS). Following the link used in the text http://www.sf-36.org/nbscalc/index.shtml , one can see the population norms for Sweden: (Mean, SD) Physical Function(ing) (87.9, 19.6), Role-Physical (83.2, 31.8), Bodily Pain (74.8, 26.1), General Health (75.8, 22.2) Vitality (68.8, 22.8), Social functioning (88.6, 20.3), Role-Emotional (85.7, 29.2), Mental Health (80.9, 18.9), Physical Composite Score (PCS) (50.0, 10) and Mental Composite Score (MCS) (50.0, 10). We are told that the Physical Function score (Median, IQR) for the unaffected twins is (48, 39-52). These are not SF-36 physical functioning scores of healthy individuals e.g. one would expect a higher median (remember that the population mean is 87.9) and one would expect a score higher than 52 as part of the IQR. Given we are given only two values, I presume what the authors mean when they say "SF-36 physical function" and "SF-36 mental function" is SF-36 Physical Composite Score (PCS) and SF-36 Mental Composite Score (MCS).

      This is important as it tells one both the health of the unaffected twins but also the health of those with Chronic Fatigue Syndrome and idiopathic chronic fatigue: a group with a physical function score (median, IQR) (41, 27-48) is quite severely affected. However, if those are Physical Composite Scores they are a relatively mildly affected cohort for CFS cases.


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    1. On 2013 Oct 25, DAVID SANDERS commented:

      Please see Monica K, 1990 "Our results show that small Mr G proteins are widely expressed in lymphoid cells and that Bcl-2 is not a novel member of this GTP-binding protein family."


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    1. On 2013 Oct 29, Jamie Horder commented:

      Salimpoor et al show using [(11)C]raclopride PET that listening to pleasant music increases dopamine release.

      Some PET and MRI facilities allow participants to listen to music during the scan - sometimes they even get to pick the songs. In the light of this study, I wonder if this practice might affect the results of studies interested in the reward system?


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    1. On 2013 Oct 28, DAVID SANDERS commented:

      Enhanced processing of mucin-deleted Ebola GP was first observed in Jeffers SA, 2002 and attributed then to more rapid transit through the secretory system.


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    1. On 2015 Apr 13, Mark Wewers commented:

      See our prior recognition of the link between NFKBIZ and interferon gamma here Raices RM, 2009.


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    1. 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 NCT0020767. We believe the correct ID, which we have found by hand searching, is NCT00207675.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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


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    1. On 2014 Nov 14, Arthur Kummer commented:

      This is an interesting perspective, although a "strictly" literary one seem more appropriate. Göethe certainly met some hyperactive children, considering the universality of the phenomenon, but definition of the disorder (i.e.: ADHD, hyperkinectic disorder etc.) suffers strong cultural influence. Thus, he may have described a hyperactive children, but not necessarily a children with ADHD. Sometimes, there is a huge difference between a phenomenon and our interpretation of it. From a literary point of view, some myths say Euphorion was the child born of the spirits of Achilles and Helen. He had perfect form and face, being the combination of beauty (Helen) and courage (Achilles). It is pretty interesting to see how Göethe creates a parallel between Faust and Achilles. Here, Euphorion is pure poetry, the combination of beauty (Helen) and the highest intellect (Faust). Indeed, Goethe described Euphorion as the "spirit of poesy", and the chorus later calls him "poesy pure" (9863), so we must also consider him from this perspective. His liveliness is pure poetry, and probably not a pathological case.


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    1. On 2016 Nov 20, Morten Oksvold commented:

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

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

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

      This article should therefore no longer be cited.


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    1. 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


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    1. On 2014 Feb 14, David Keller commented:

      Ibuprofen use is associated with lower risk of Parkinson's Disease

      In the March 8, 2011 issue of Neurology (published online on March 2), a large prospective study by Gao demonstrated that users of ibuprofen had a significantly lower risk of developing Parkinson's Disease (PD) than non-users (relative risk = 0.62, p=0.02). He also demonstrated a significant dose-response relationship between the number of tablets of ibuprofen taken per week and reduction of PD risk. In addition, he found that PD risk was not significantly affected by the use of other NSAID's or aspirin. Gao also published a meta-analysis of prior studies, which revealed a highly significant relative risk of 0.73 for ibuprofen users developing PD, versus no benefit for users of other NSAID's.

      I believe that the results cited above render the findings of the Driver study irrelevant with respect to ibuprofen, since Driver grouped together users of all NSAID's. By failing to separately analyze ibuprofen, its possible benefits may have been diluted out by the non- beneficial effects of other NSAID's.

      It is imperative at this time that ibuprofen be studied further as a possible neuro-protective agent in PD. The null results of the Driver study should be ignored. The best available evidence clearly supports funding for a prospective, randomized, double-blind placebo-controlled interventional trial of ibuprofen as a neuro-protective agent in early Parkinson's Disease.


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    1. On 2014 Jul 14, David Reardon commented:

      Given the excellence of this data set, it is unfortunate that the researchers failed to consider the methodology employed in prior record based studies of abortion and mental health (for example, Reardon DC, 2003 and Coleman PK, 2002) and instead made choices which tend to confound rather than clarify the issues at hand.

      Perhaps the biggest problem is the failure to examine pre-pregnancy mental health. This was done in prior studies which controlled for psychiatric admissions for at least one year prior to the calculated date of conception (Reardon DC, 2003). Instead, Munk-Olsen chose as a base line for mental health a nine month period prior to pregnancy outcome, a period covering the entire period of pregnancy for delivering women and approximately three months of pregnancy and six months pre-pregnancy for women who aborted.

      This poorly explained decision unfortunately introduces elements of an apples versus oranges comparison.

      This is problematic for two key problems. First, it totally ignores the pre-pregnancy mental health of delivering women. Women who are excited about having a baby may be less likely to seek mental health. With only a nine-month pre-event window, the authors are even excluding those women who may have been experiencing anxiety or depression if they were struggling to become pregnant.

      Secondly, for aborting women, it includes two to three months of a period in the women's lives which is likely highly stressful since these women are, it must be presumed, facing discovery of an unplanned pregnancy and potential conflicts over this with partners, parents, and others. This nine month window therefore not only fails to provide a base line for mental health prior to the subjects' pregnancy but mixes, several months of pre-pregnancy mental health with one or more months of post-pregnancy, pre-abortion stress.

      These study design criteria are not only unprecedented in similar studies but simply contrary to the stated objective of controlling for prior mental health. This failure in design is even more puzzling given the fact that the available data set included mental health information for the entire life of the women in the study. Given the availability of all prior mental health treatment dates, it seems self evident that the researchers should have created a scale for exposure to prior mental health treatments prior to the estimated conception date of each woman's first pregnancy covering at least one full year, preferably five years, and perhaps for each subject's entire life.

      Given the fact that the authors only exclusion criteria was a history of inpatient psychiatric treatment, we must assume that since the mental health of both groups was relatively similar prior to becoming pregnant. The three fold increase in mental health treatments prior to abortion (14.6 per 1000 yrs) compared to women who gave birth (3.9 per 1000 yrs) would therefore appear to be most likely explained by stress these women faced discovering they were faced with an unplanned pregnancy and, in many cases, the concurrent disruption of relationships with male partners, parents, employers and others.

      In addition, aborting women were more likely to involved in unstable and possibly abusive relationships prior to their pregnancies. It is not surprising, then, that many of these women facing the stress of abortion decision-making sought psychiatric advise at a much more elevated rate than they had in the past.

      The lack of pre-pregnancy mental health measure, in itself, renders it impossible to draw general conclusions regarding from this study. But there are also numerous additional problems with the study design that further confound the results and interpretation:

      • The study excluded women who are most likely to have the most severe reactions to an abortion, namely those who already had a prior history of abortion, those with a prior history of inpatient mental health treatment. It also excluded women who died prior to one year after the pregnancy event, thereby excluding women who committed suicide, even though a record linkage study from neighboring Finland found a six fold higher rate of suicide in the year following abortion compared to the year following childbirth (Gissler M, 1996).

      • The study failed to keep women in the two groups separate. Women who had both an abortion and delivery were included in both parts of the analysis groups. This is especially problematic given the evidence women with a prior history of abortion have more stress during and after subsequent pregnancies (Coleman PK, 2002). As a result, by putting women with a history of abortion in the group of delivering women, the "control" group may be adulterated with the very post-abortion effects this study professes to be exploring. The authors should have limited the study to first pregnancy outcome, and should also have included first pregnancies ending in miscarriage, still birth, and other natural losses as a third group.

      • The outcome variable used for this study was limited to only a single psychiatric treatment. It did not measure or give any weight to repeated treatments or multiple mental health problems in an effort to evaluate the severity or duration of mental health problems associated with pregnancy outcomes. It should also be noted that the authors' conclusions are not consistent with their data. Specifically, the authors conclude: "our study shows that the rates of a first-time psychiatric contact before and after a first-trimester induced abortion are similar." The fact that many of the psychiatric contact rates during the nine months preceding an abortion were similar to the contact rates in the year following an abortion were statistically insignificant does not alter the fact that, even with all of the problems in the methodology identified above, their data also showed several statistically significant higher rates for specific mental disorders.

      Specifically, as seen in table 1, contact rates for neurotic, stress-related or somatoform disorders were higher in every two month period following an abortion, and was statistically significant in two of the six periods. Similarly, for personality or behavioral disorders, the relative risk was higher for four of the six periods and significantly higher for two of the six periods. In other words, when one actually examines the table of reported findings, the conclusion that "in some cases the rate of a first-time psychiatric contact is significantly higher following an abortion compared to the nine months preceding an abortion" is at least equally true, and arguably more accurate.

      Finally, I would note that at least one of the authors, Laursen, was also a co-author of an excellent record linkage study from Demark examining mental illness among parents of deceased children that was also published in the New England Journal of Medicine.(Li J, 2005) That study design examined long term mental health effects, beyond one year, and controlled for exposure to multiple losses, and had none of the selection bias problems identified in this Munk-Olesn study.

      This exact study design could have, and should have, been used simply by plugging the date of exposure to induced abortion into the same fields used for date of exposure to the death of a child. By using a proven study design in this way, Munk-Olsen and Laursen could have avoided the impression (in this case, the very profound impression) that this new study design (with a nine month pre-event control period and intermixing of subjects into both the abortion group and delivery group, et cetera) was artificially constructed precisely to minimize the number of statistically significant findings associating abortion with increased mental health treatments. In conclusion, this study does nothing to impute previous record linkage studies showing elevated rates of psychiatric treatments following induced abortion.


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    1. On 2015 Sep 27, Raechel Damarell commented:

      The Heart Failure Search Filter is available on the Flinders Filters webpage at http://www.flinders.edu.au/clinical-change/research/flinders-filters/search-filters/. Other validated topic filters available include: dementia, bereavement, residential aged care, glaucoma, contraception, and lung cancer.


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    1. On 2014 Feb 28, Zhongheng Zhang commented:

      A good work provided link between BNP and NF-KB pathway.


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    1. On 2013 Dec 10, Lorene M Nelson commented:

      None


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    2. On 2013 Dec 10, Lorene M Nelson commented:

      None


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    3. On 2013 Dec 10, Lorene M Nelson commented:

      Note from senior author: Please note that a reply to the letter by Hill-Burns et al. ("An attempt to replicate interaction between coffee and CYP1A2 gene in connection to Parkinson's disease") 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 our reply letter: Popat RA et al., Eur J Neurol 2011;18:e109.


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    1. On 2015 Jul 24, Md. Shahidul Islam commented:

      More updated information on the TRP channels in the islets are available in the following chapter by the same author: "Calcium Signaling in the Islets", 2014, Islets of Langerhans, 2nd ed. Springer, ISBN: 978-94-007-6884-0.


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    1. On 2013 Oct 23, Rae Thomas commented:

      We recently presented this paper at our Journal Club to discuss “How could meta-analyses convey meaningful results regarding effective interventions in child mental health to clinicians?”

      There seems a lack of evidence-based treatments provided to children within child mental health settings •Hoagwood & Olin, 2002 reported 90% of publicly funded child mental health services didn’t use EBTs •Allen, Gharagozloo, & Johnson, 2012 reported clinicians could identify less than 2/5 expert nominated EBTs from a list of 15 •Thomas, Zimmer-Gembeck, & Chaffin, 2013 reported 58% of clinicians could defined an EBT using broad criteria and indicated use but 24% identified broad frameworks and of those 58% of actual EBTs in use, 88% of clinicians said they modified the EBTs

      Previous meta-analyses considered intervention effectiveness using other variables •Individual interventions (Geeraert et al., 2004) •Settings (e.g., clinic vs home; Selph et al., 2013) •Components of interventions (Kaminski et al., 2008) •Components and Implementation of interventions (Durlak et al., 2011)

      Our Group Discussion •Because of intervention heterogeneity, often meta-analyses in these formats provide little information for clinicians about what intervention is most effective for which population, even so, cost to implement an intervention may be prohibitive for some organisations. In this paper, effects of social and emotional learning programs were moderated by how the program was implemented. •A meta-regression of studies to consider the unique contributors to effective interventions may provide more useful information to clinicians (i.e., quality of studies, components of effective interventions). However, if possible, clinicians should be given both options (i.e., an effective intervention and components of effective interventions).


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    1. On 2016 Mar 18, ZHONGMING ZHAO commented:

      My lab recently moved to the University of Texas Health Science Center at Houston. The source code is now available at https://www.uth.edu/bioinfo/software.htm.


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    1. On 2016 Sep 06, Hilda Bastian commented:

      The conclusions of this review are not supported by the findings of the studies included in it, and much of the evidence cited contradicts the authors’ conclusions. The review suffers from extensive methodological weaknesses, particularly study selection bias and selective reporting. Out of hundreds of studies that were likely to be eligible in the 3 main areas they address (Dehdarirad, 2015), they include only 35. It is not a review of 20 years of data: it is a review based on selected data from the last 20 years. The basis for that selection is not reported.

      Their description of the results of these studies includes, in my opinion, severe levels of 2 key types of review spin (Yavchitz A, 2016): misleading reporting and misleading interpretation. The review contains numerous errors in key issues such as reporting numbers and the methodology of studies. Conclusions about the quality of some evidence are drawn by the authors, but the basis for these judgments is unclear and no methodical process for assessing quality is reported or evident.

      The 3 main areas covered by the review – journal publications, grant applications, and hiring – are also at high risk of publication bias, which is not addressed by the review. Discrimination against women is the subject of legislation in most, if not all, the countries in which these studies were done. Journals, funding agencies, and academic institutions may not be enthusiastic about broadcasting evidence of gender bias.

      For example, of the many thousands of science journals published in 2011, only 6 studies are cited, conducted in 8 to 13 journals in 2 areas of science. In one of those, the author approached 24 journals: only 5 agreed to participate (Tregenza, 2002).

      Ceci and Williams conclude that only 4 of the 35 unique studies they cited suggest the possibility of some gender bias. However, in my opinion an additional 7 studies clearly concluded gender bias remained a problem needing consideration, and others found signs suggesting bias may have been present. Altogether, in 19 studies (54%), there is either selective reporting and descriptions that spin study results in the direction of this review’s conclusions, or inaccurate reporting that could affect the weight placed on the evidence by a knowledgeable reader.

      I identified no instance of spin that did not favor the authors’ conclusions. Some of the studies referenced did not address the questions for which they were cited. Several are short reports in letters, 1 relies on a press release, and another is a news report of a talk.

      Variations in disciplines are not adequately addressed. The authors concentrate on time periods as critical, but the evidence shows that not all disciplines have reached the same level of development in relation to gender participation. Issues related to international differences, and different experiences for groups of women who may experience additional discrimination are not addressed. Although the conclusions are universally framed, they do not address women in science outside academia.

      The authors address only 3 possible explanations for women’s underrepresentation in science: discrimination, women’s choices and preferences (especially relating to motherhood), and gender differences in mathematics ability. They argue that only women’s choices, particularly in relation to family, are a big enough factor to explain women’s underrepresentation. What is arguably the dominant hypothesis in the field is not addressed: that men are overrepresented in science because of cumulative advantage. Advantages do not have to be large individually, to contribute to the end result of underrepresentation in elite institutions and positions. (I have also commented on another paper in which they advance their hypothesis about motherhood and women scientists (Williams WM, 2012) - link to comment.)

      In addition, they do not address the full range of issues within the 3 areas they consider. For example, in grants and hiring, they do not address analyses of potential bias in letters of recommendation (e.g. Van Den Brink, 2006, Schmader T, 2007).

      In my opinion, this review is irredeemably flawed and should be retracted.

      My methodological critique and individual notes on studies are included at my blog.

      Disclosures: I work at the National Institutes of Health (NIH), but not in the granting or women in science policy spheres. The views I express are personal, and do not necessarily reflect those of the NIH. I am an academic editor at PLOS Medicine and on the human ethics advisory group for PLOS One. I am undertaking research in various aspects of publication ethics.


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    2. On 2016 Oct 12, Stephen Ceci commented:

      Below Hilda Bastian criticizes our 2011 article in the Proceedings of the National Academy of Sciences. The criticisms reflect a simplistic rendering of the rich data landscape on women in academic science. Our conclusion was valid in 2011 and since then new scholarship has continued to support it. Below is an abbreviated response to Bastian’s claims, but a somewhat longer account can be found at: http://www.human.cornell.edu/hd/ciws/publications.cfm Claim 1: Our work failed to represent all research on the topic. This criticism does not take into account the quality of the research and the need to use judgment on study inclusion. Rather than calculate mean effect sizes based on all published studies, it is important to down-weight ones that have been refuted or supplanted. We did this in our narrative review in 2011. Nothing we wrote has changed and the intervening research has reinforced our conclusion of gender-neutrality in journal reviews, grant reviews, and tenure-track hiring. For example, Marcia McNutt, editor of Science, wrote "there was some good news from a panel representing major journals…such as the American Chemical Society (ACS) and the American Geophysical Union (AGU)…female authors are published either at a rate proportional to that at which they submit to those journals, or at proportionally higher rates, as compared with their male colleagues." McNutt, 2016, p. 1035) This may surprise those who read claims that women were selected as reviewers less often than their fraction of the submission pool, but it is true: women’s acceptance rates were, if anything, in excess of men’s. This is not cherry-picking, nor can it be erased by aberrations. These are large-scale analyses of acceptance rates of major journals, and it shows the landscape is either gender-fair or women actually have an advantage—in contrast to what Dr. Bastian alleges. The same is true of funding. To illustrate why it is important to move beyond factoring all the studies into a mean effect size, we offer three examples at http://www.human.cornell.edu/hd/ciws/publications.cfm For example Bornmann et al.’s finding of gender bias in funding using a large sample of grant applications. However, Marsh et al. reanalyzed these findings using a multilevel measurement model and arrived at a different conclusion. Bornmann himself was a coauthor on the Marsh et al. publication and agreed that the new finding of gender-neutrality supplanted his earlier one of gender bias. Marsh et al. found that the mean of the weighted effect sizes based on the 353,725 applicants was actually +.02--in favor of women! (see p. 1301): "The most important result of our study is that for grant applications that include disciplines across the higher education community, there is no evidence for any gender effects in favor of men, and even some evidence in favor of women…This lack of gender difference for grant proposals is very robust, as indicated by the lack of study-to-study variation in the results (nonsignificant tests of heterogeneity) and the lack of interaction effects. This non effect of gender generalized across discipline, the different countries (and funding agencies) considered here, and the publication year.” (p. 1311) Marsh, Bornmann, et al. (2009) (DOI: 10.3102/0034654309334143)

      The rest of our paper concerned hiring and journal publishing. We stand by our conclusion in these two domains as well, as the scientific literature since then has supported us. We do not have time or space here to describe in detail the evidence for this assertion, but the interested reader can find much of it in our over 200 analyses (http://psi.sagepub.com/content/15/3/75.abstract?patientinform-links=yes&legid=sppsi;15/3/75 DOI:10.1177/1529100614541236)Unsurprisingly, the PNAS reviewers were knowledgeable about these domains and agreed with our conclusion. It is incumbent on anyone arguing otherwise to subject their evidence to peer review and show how it overturns our conclusion. Does our claim that gender bias in hiring and publishing lacks support mean there are no gender barriers? Of course not; we have written frequently about them: we have discussed an article that Bastian appears to believe we are unaware of—showing differences in letters of recommendation written for women and men. And we have written about other barriers facing women scientists, such as their teaching ratings downgraded and their lower tenure rates in biology and psychology. However, we stand by our claim that the domains of hiring, funding, and publications are largely gender-neutral. Unless peer reviewers who are experts in this area agree there is compelling counter-evidence, we believe our conclusion reflects the best scientific evidence. Claim 2: We failed to specify what we meant by “women”. Bastian points out differences between women of color, class, etc. We agree these are potentially important moderating factors and we applaud researchers who report their data broken down this way. But the literature on peer review, funding, and hiring rarely reports differences by ethnicity, class, or sexual orientation. Most of the few studies to do so emerged after our study was published. Claim 3: Bastian criticized us for not taking into consideration the size and trajectory of fields, suggesting those with large numbers of scholars may overwhelm smaller ones, or the temporal trajectory of some fields is ahead of others. Field-specific gender differences are a valid consideration but in funding they have been small or non-existent according to several large-scale analyses. Jayasinghe et al.’s (2004) comprehensive analysis of gender effects in reviews of grant proposals (10,023 reviews by 6,233 external assessors of 2,331 proposals from 9 different disciplines), found no gender unfairness in any discipline nor any disciplinary x gender. If anyone has compelling evidence of disciplinary bias against women authors and PIs, they should submit it and allow the peer review process judge how compelling it is. As far as differences among fields in their trajectories, we have done extensive analyses on this, which can be found at the same site above. In these analyses we examined temporal changes in 8 disciplines in salary, tenure, promotion, satisfaction, productivity, impact, etc. With some exceptions we alluded to above, the picture was mainly gender-fair. Finally, Bastian raises analytic issues. We agree these are central. This is why we minimized small-scale, poorly-analyzed reports. We gave more attention to large journals and grant agencies that allowed multilevel models, instead of or in addition to Fixed and Random effects analyses that sometimes violated fundamental statistical assumptions. Both Fixed effect and Random-effects models have limitations. (The latter assumes features of the studies themselves contribute to variability in effect sizes independent of random sampling error, whereas multilevel models permit multiple outcomes included without violating statistical assumptions such as the independence of effect sizes from the same study due to using the same funding agency or multiple disciplines within the same funding agency.) Mean effect sizes are not the analytic endpoint when there is systematic variation among studies beyond that accounted for by sampling variability, which is omnipresent in these studies; it is important to determine which study characteristics account for study-to-study variation. In the past, some have cherry-pick aberrations to support claims of bias, and our 2011 report went beyond doing this to situate claims amidst large-scale, well-analyzed studies, minimizing problematic studies. Although women scientists continue to face challenges that we have written about elsewhere, these challenges are not in the three domains of tenure-track hiring, funding, and publishing.

      Steve Ceci and Wendy M. Williams


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    1. On 2014 Aug 11, Tom Kindlon commented:

      Estimate for prevalence of CFS in the population may be an underestimate:

      Many people affected by chronic fatigue syndrome (CFS) are unable to work [1-3]. This suggests to me that the sample was not ideal to estimate the prevalence of CFS, and presumably a more representative sample would find a higher prevalence.

      Extract:

      Design and setting:

      We designed a cross-sectional study to assess the characteristics of Japanese with CFS in participants in a medical health checkup program at Murakami Memorial Hospital, Gifu, Japan. We randomly invited 3000 participants to enroll in the study, who received the health checkup programs between September 2006 and August 2007. The study was approved by the ethics committee of Murakami Memorial Hospital.

      The purpose of medical health checkup programs are to promote public health through early detection of chronic diseases and their risk factors. Medical service of this kind, known as“a human dock,”is very popular in Japan [37]. The health checkup center at Murakami Memorial Hospital was founded in 1994 and is currently performing health checkups in more than 8000 examinees annually. Most of the participants were employees of private companies and local governmental organizations in Gifu, Japan, and their spouses. These companies and organizations recruit employees each year according to requires recruits to be checked in Murakami Memorial Hospital. The cost of the medical examination was largely paid for by the employers. Fewer than 10% of the participants individually registered in this program and paid checkup-costs by themselves, and they were all citizens of local communities.

      Also

      “All the CFS participants, who answered short sleep duration, unrefreshing sleep, disturbance of sleep, and/or insufficient sleep, stated that their sleep duration was inadequate because of social factors, mainly job-related ones.” – 13 of 14 CFS patients had sleep problems suggesting many/most of those with CFS in the sample were working.

      References:

      1. Comiskey C, Larkan F. A national cross-sectional survey of diagnosed sufferers of myalgic encephalomyelitis/chronic fatigue syndrome: pathways to diagnosis, changes in quality of life and service priorities. Ir J Med Sci. 2010 Dec;179(4):501-5.

      2. Collin SM1, Crawley E, May MT, Sterne JA, Hollingworth W; UK CFS/ME National Outcomes Database. The impact of CFS/ME on employment and productivity in the UK: a cross-sectional study based on the CFS/ME national outcomes database. BMC Health Serv Res. 2011 Sep 15;11:217.

      3. Reynolds KJ, Vernon SD, Bouchery E, Reeves WC. The economic impact of chronic fatigue syndrome. Cost Eff Resour Alloc. 2004 Jun 21;2(1):4.


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    1. On 2014 Mar 09, Gyanshankar Mishra commented:

      We did further studies on complete pulmonary function profile in Diabetics with COPD or Asthma. available online at http://www.applied-cardiopulmonary-pathophysiology.com/05_mishra.html


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    1. 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 NCT003311032. We believe the correct ID, which we have found by hand searching, is NCT00331032.

      This comment is being posted as part of the OpenTrials.net project<sup>[1]</sup> , 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


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    1. On 2014 Nov 21, Gerhard Nebe-von-Caron commented:

      This work is unfortunatelly missing appropriate revision. There is no evidence that the authors observed single bacteria due to the fact that no pictures of scatter versus nucleic acid fluorescence are shown. It would be recommended that the authors submit the raw data listmode files to http://flowrepository.org/ for validation. The fact that the picture in their 2010 poster "Flow cytometry as a means of observing the effects of ultrasound on bacteria" shows scatter data and antibody fluorescence of white blood cells instead of bacteria and regions of interest that indicate a lack understanding of the data analysis made me search for a follow up paper from the authors and my suspicion was confirmed in this paper. For example there is no distinction made between bacteria and noise signals. Figure 5 and 7 show the settings of quadrants cutting across clusters which is scientifically incorrect, and some of the clusters are in part likely to be caused by trigger artefacts. Figure 5e include permeabilised cells and DNA negative events in the lower left quadrant which could be pumping cells, cell debris as well as bubbles and micelles, distinguishable by appropriate data analysis.

      The conclusion "Although flow cytometry data were comparable to viable plate count techniques, the percentage of live cells appeared higher. This observation is considered to be almost certainly because of the ability of flow cytometry to identify and count bacteria as single cells, whereas viable plate counts only enumerate colony forming units (CFUs) which can be either single bacterial cells or agglomerates of cells" indicates a lack of understanding of the measurement principles. Apart from the problems of colony formation, discussed in several of my publications, when measuring bacteria, cell aggregation can only be detected if genome equivalents are measures or one realises that double positive cells in case of energy transfer staining combinations represent two cells with one red and permeabilised and another green and intact, either coincident or still attached to each other. Most instruments unless aligned and maintained to the standards required for microbial analysis will not detect bacteria adequately when triggering on forward scatter. Thus the separation of bacteria from instrument noise needs to be demonstrated and a comprison of the data should be based on absolute counts. Also the use of aggregated bacteria would have been preferential to compare the effect of disaggregation compared to cellular injury as an indicator for the delivered energy on the membrane.


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    1. On 2015 Apr 22, Bernard J Crespi commented:

      With regard to interpretation of the results of this article, do note that of the four schizophrenia patients described here with maternal duplications, one had a duplication that spanned BP1-BP3, two showed duplications of BP2-BP3, and one had a duplication from BP1 to a region between BP4 and BP5. By contrast, of the comparison subjects with maternal duplications, two had BP1-BP3 duplications and one had a duplication of BP2-BP3. These duplications are thus rather heterogeneous, which complicates inferences regarding causation.

      Restricting the analysis to the BP2-BP3 region (and noting also that BP1-BP2 region deletions have been associated statistically with schizophrenia in previous work), yields two patients and one control with the maternal duplication (Fisher’s exact test, p = 0.061). If the BP2-BP3 duplication is considered regardless of parental origin, then two patients and two controls show the duplications (Fisher's exact test, P = 0.10). It would thus be useful if, at some point, further analysis could be done with larger samples of individuals with relevant duplications.

      With regard to the causal genes, a newly-published study (Noor et al. 2015) shows that duplications encompassing just the maternally-expressed, imprinted gene UBE3A, which is in the BP2-BP3 region, segregate with psychiatric diagnoses including schizophrenia, anxiety and depression, in an extended pedigree.

      Reference

      Noor A, Dupuis L, Mittal K, Lionel AC, Marshall CR, Scherer SW, Stockley T, Vincent JB, Mendoza-Londono R, Stavropoulos DJ. 15q11.2 Duplication Encompassing only the UBE3A Gene is Associated with Developmental Delay and Neuropsychiatric Phenotypes. Hum Mutat. 2015 Apr 17. doi: 10.1002/humu.22800.


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    1. On 2015 Nov 25, Uday Yanamandra commented:

      The second author name Uday Y should read as Yanamandra U.


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    1. On 2014 Dec 06, Harri Hemila commented:

      Errors in the Cochrane review (2011) on zinc for the common cold

      The Cochrane review (2011) on zinc for the common cold by Singh M, 2011; DOI; had a number of problems, which were commented on in detail in a separate document. Here the problems in the Cochrane review (2011) are listed and briefly described:

      1) Search of the studies was not thorough. Singh M, 2011 did not include Eby GA, 2006 although that study was listed in Pubmed with keywords zinc and the common cold.

      2) There were errors in the extraction of data. In Fig. 3 (p.15) Singh M, 2011 claimed that in the Petrus 1998 study (http://dx.doi.org/10.1016/S0011-393X(98)85058-3), the duration of colds in the zinc group was 4.4 days, whereas Petrus reported 3.8 days for the zinc group, see the link.

      3) The characteristics of included studies table had errors and was not consistent in describing the included trials.

      4) The characteristics of excluded studies table had errors. For example, Singh M, 2011 (p.39) claimed that the study by Turner RB, 2000 was “Not a randomised trial” though the study report clearly describes that the trial was randomised, see pp.1202-3 in DOI.

      5) Different methods of administering zinc should be analyzed separately, whereas Singh M, 2011 pooled all together. Some studies administered zinc as syrup or tablets, some as lozenges. It is probable that the benefit of zinc in syrup and tablet trials is caused by biological mechanisms that are different from the mechanisms of the zinc lozenges, which are intended to be dissolved slowly in the mouth, see eg Hemilä H, 2011 and Eby GA, 2004. Combining different methods of zinc administration is the classical apples and oranges problem of meta-analysis.

      6) The duration of the common cold should not be arbitrarily dichotomized as was done in Analyses 2.1 to 2.3 (pp.43-5) by Singh M, 2011. Duration is a continuous variable and should be analyzed as a continuous variable. The results of the zinc lozenge studies can be and should be analyzed using cold duration as a continuous variable, see Hemilä H, 2011.

      7) Duration of the common cold should have been normalized so that placebo groups have length 100%. There is substantial variation in the duration of colds in the placebo groups of the zinc lozenge trials, from 5.1 days to 9.0 days and 10.8 days, see Hemilä H, 2011. For example, if a 5-day cold is shortened by 4 days, it is not equivalent to a 11-day cold being shortened by 4 days although both differences are equal in absolute units. The former is an 80% decrease in duration, whereas the latter is only a 36% decrease. Although part of the placebo group variation is caused by random variation, it is also caused by differences in viruses and in the severity of disease in different patient groups, and in differences in outcome definitions. Therefore, the relative effect of zinc on the common cold duration should be calculated in percentages, because the relative effect partly adjusts for the variations between patient groups and outcome definitions. In another study, the results of the zinc lozenge studies were analyzed as percentage effects, see Hemilä H, 2011.

      8) Subgroup analysis should have been carried out. In the Background section (p.6), Singh M, 2011 wrote that a “significant correlation between total daily dosages of positively charged zinc species and a reduction in the mean duration of common colds” has been reported, however, they did not analyze that question. In the zinc lozenge studies, there is a 6-fold variation in the total zinc dose from 30 to 207 mg per day, see Hemilä H, 2011. Dose-response relation is a basic concept in pharmacology and thus the relation between dose and the effect of zinc lozenges should have been analyzed in the Cochrane review (2011). Hemilä H, 2011 found that none of the low zinc dose studies found effects of zinc lozenges, whereas high zinc dose studies found very strong evidence that colds were shortened by zinc. Such findings are consistent with the dose-response concept.

      9) Pooling the adverse effects of all zinc trials is unsound, yet Singh M, 2011 did so in Fig. 6 (p.18). Eby GA, 2004 pointed out that the adverse effects of zinc lozenges, such as bad taste, can be explained largely by the differences in the composition of the lozenges. Furthermore, it is obvious that dissolving a zinc lozenge slowly in the mouth causes different adverse effects compared with ingesting a zinc syrup or tablet straight to the stomach. There is no justification to pool adverse effects of all zinc trials together, ignoring the considerable variations in the zinc products. As to the zinc lozenges, Eby GA, 2004 commented that “although pure zinc gluconate is bland and chalky in taste, it reacts with dextrose and related carbohydrates (excluding fructose) upon aging of lozenge compositions to produce noisome bitterness... On the other hand, zinc acetate allows the production of pleasant tasting, flavor stable lozenges”. In the most recent zinc acetate lozenge trial, Prasad AS, 2008 found no significant differences between the zinc and placebo groups in the occurrence of adverse effects although the daily dose of zinc was 92 mg.

      10) Credit should be given to earlier work on the same topic. In the Introduction, Singh M, 2011 (p.7) wrote “The last review of all available RCTs of zinc for the common cold was published in 1999”, which is false. Reviews on zinc and the common cold by Jackson JL, 2000 and Caruso TJ, 2007 were published after 1999 and should have been mentioned as previous reviews on the same topic.

      There is much evidence to indicate that high doses of zinc as zinc lozenges have effects on the duration of colds, see Hemilä H, 2011 and Eby GA, 2004. Therefore the topic of Singh M, 2011 is important; however, there were numerous methodological problems which limited the relevance of the conclusions.

      Singh M, 2011 concluded that “In view of this and the differences in study populations, dosages, formulations and duration of treatment, it is difficult to make firm recommendations about the dose, formulation and duration that should be used.”

      Had Singh M, 2011 separately analyzed the syrup and tablet studies and the lozenge studies, and had they analyzed the relation between the dose and effect, they could have reached much more clear conclusions.

      Hemilä H, 2011 limited analysis to the zinc lozenge studies and found that five trials that used the lowest doses of zinc uniformly found no effect. Three trials used zinc acetate in daily doses of over 75 mg, and the pooled result indicated a 42% reduction in the duration of colds (95% CI: 35% to 48%). Five trials used zinc salts other than acetate in daily doses of over 75 mg, the pooled result indicating a 20% reduction in the duration of colds (95% CI: 12% to 28%). Thus, clear conclusions for patients and for further research could have been drawn from the studies that were available to Singh M, 2011.


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    1. On 2014 Nov 24, Tom Kindlon commented:

      Letter published criticising threshold for normal functioning used in PACE Trial:

      Bleijenberg and Knoop claimed a strict criterion for recovery was used in the PACE Trial. A letter has been published challenging this: it quotes some population data to show how ridiculous a threshold of 60+ on the SF-36 physical functioning is to define "normal functioning" and recovery (particularly in the PACE Trial given its own entry criteria).

      Kindlon T, Baldwin A. Response to: reports of recovery in chronic fatigue syndrome may present less than meets the eye. Evid Based Mental Health doi:10.1136/eb-2014-101961 http://ebmh.bmj.com/content/early/2014/09/19/eb-2014-101961.extract


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    2. On 2016 Sep 27, Alem Matthees commented:

      The 'normal range' was not a strict criterion for recovery nor was it based on healthy scores

      The editorial by Bleijenberg & Knoop (2011) contains a misleading statement: “PACE used a strict criterion for recovery: a score on both fatigue and physical function within the range of the mean plus (or minus) one standard deviation of a healthy person’s score. In accordance with this criterion, the recovery rate of cognitive behavioural and graded exercise therapy was about 30%—although not very high, the rate is significantly higher than that with both other interventions.” [1]

      However, the PACE publication did not report on "recovery" [2] and the PACE authors issued a statement to that effect [3] despite previously approving the editorial before it was published [4,5]. The normal range overlapped with trial eligibility criteria for severe disabling fatigue [2]. The largest overlap was with SF-36 physical function, where 13% of participants simultaneously met the normal range on this measure and the entry criteria for "significant disability" [6]. The individual participant data recently released from the PACE trial reveals that 45% (60/134) of those within the normal range at 52-week follow-up still met Oxford CFS criteria [7].

      It is disappointing that the Lancet and Bleijenberg & Knoop stand by the comment on recovery despite being alerted of the problems [5]. The Press Complaints Commission ruled that the editorial was misleading [4,5]. Oddly enough, both Bleijenberg & Knoop have previously co-authored papers where a score of 60 (the threshold for normal physical function) was regarded as severe impairment [8-11].

      The normal range was not based on healthy people of working age only. For example, the normal range for physical function was based on a general population that included the elderly and chronically disabled [3]. If the normal range was based on a healthy population as asserted, the threshold for normal physical function would be 85 points or more, not 60 or more [6]. A preliminary re-analysis of recovery in the PACE trial, based on the protocol-specified recovery criteria, shows that the recovery rates in the CBT and GET groups were 6.8% and 4.4% respectively, and not significantly higher than with specialist medical care alone [7].

      References

      1) Bleijenberg G, Knoop H. Chronic fatigue syndrome: where to PACE from here? Lancet. 2011 Mar 5;377(9768):786-8. doi: 10.1016/S0140-6736(11)60172-4. Epub 2011 Feb 18. PMID: 21334060. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60172-4/fulltext

      2) White PD, Goldsmith KA, Johnson AL, Potts L, Walwyn R, DeCesare JC, Baber HL, Burgess M, Clark LV, Cox DL, Bavinton J, Angus BJ, Murphy G, Murphy M, O'Dowd H, Wilks D, McCrone P, Chalder T, Sharpe M; PACE trial management group. 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 Mar 5;377(9768):823-36. doi: 10.1016/S0140-6736(11)60096-2. Epub 2011 Feb 18. PMID: 21334061. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065633/

      3) 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, Volume 377, Issue 9780, Pages 1834 - 1835, 28 May 2011 (Published Online: 17 May 2011). doi:10.1016/S0140-6736(11)60651-X http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60651-X/fulltext

      4) http://www.pcc.org.uk/cases/adjudicated.html?article=ODQwOQ

      5) Continuing Correspondence Between Countess of Mar and Professor Peter White and Professor Sir Simon Wessely. 26 January 2013. http://forums.phoenixrising.me/index.php?threads/continuing-correspondence-countess-of-mar-and-prof-white-and-prof-sir-s-wessely.21545/

      6) Matthees A. Re: Tackling fears about exercise is important for ME treatment, analysis indicates. BMJ Rapid Response. 21 January 2015. http://www.bmj.com/content/350/bmj.h227/rr-16

      7) Matthees A, Kindlon T, Maryhew C, Stark P, Levin B. A preliminary analysis of ‘recovery’ from chronic fatigue syndrome in the PACE trial using individual participant data. Virology Blog. 21 September 2016. http://www.virology.ws/wp-content/uploads/2016/09/preliminary-analysis.pdf

      8) van't Leven M, Zielhuis GA, van der Meer JW, Verbeek AL, Bleijenberg G. Fatigue and chronic fatigue syndrome-like complaints in the general population. Eur J Public Health. 2010 Jun;20(3):251-7. Epub 2009 Aug 18. PMID: 19689970. http://eurpub.oxfordjournals.org/content/20/3/251.long

      9) Tummers M, Knoop H, van Dam A, Bleijenberg G. Implementing a minimal intervention for chronic fatigue syndrome in a mental health centre: a randomized controlled trial. Psychol Med. 2012 Oct;42(10):2205-15. doi: 10.1017/S0033291712000232. Epub 2012 Feb 21. PMID: 22354999. http://www.ncbi.nlm.nih.gov/pubmed/22354999

      10) Stulemeijer M, de Jong LW, Fiselier TJ, Hoogveld SW, Bleijenberg G. Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial. BMJ. 2005 Jan 1;330(7481):14. Epub 2004 Dec 7. doi: 10.1136/bmj.38301.587106.63. PMID: 15585538. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC539840

      11) Heins M, Knoop H, Nijs J, Feskens R, Meeus M, Moorkens G, Bleijenberg G. Influence of symptom expectancies on stair-climbing performance in chronic fatigue syndrome: effect of study context. Int J Behav Med. 2013 Jun;20(2):213-8. doi: 10.1007/s12529-012-9253-2. PMID: 22865100. http://www.ncbi.nlm.nih.gov/pubmed/22865100


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    1. On 2013 Nov 15, Ellen M Goudsmit commented:

      As a co-author of the London criteria for myalgic encephalomyelitis, I wish it to be known that this stdy did not use the criteria and that their citation refers to an incomplete and flawed version written by someone without permission from the original authors. It is therefore unclear if there were any patients with ME who participated in this trial.

      Dr E Goudsmit PhD FBPsS


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    2. On 2014 Sep 28, Tom Kindlon commented:

      Letter published criticising the threshold for normal functioning and recovery in the PACE Trial:

      Quotes some population data to show how ridiculous a threshold of 60+ on the SF-36 physical functioning is to define "normal functioning" and recovery.

      Kindlon T, Baldwin A. Response to: reports of recovery in chronic fatigue syndrome may present less than meets the eye. Evid Based Mental Health doi:10.1136/eb-2014-101961 http://ebmh.bmj.com/content/early/2014/09/19/eb-2014-101961.extract


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    3. On 2015 Oct 23, Lily Chu commented:

      No study is perfect but this trial suffered from some major flaws. These are covered by Dr. David Tuller in the following link:

      http://www.virology.ws/2015/10/21/trial-by-error-i/


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    4. On 2016 Jan 08, Tom Kindlon commented:

      "Trial By Error, Continued: Did the PACE Trial Really Prove that Graded Exercise Is Safe?"

      By two journalists: Julie Rehmeyer is a journalist and Ted Scripps Environmental Journalism Fellow at the University of Colorado, Boulder, who has written extensively about ME/CFS.

      David Tuller DrPH is academic coordinator of the concurrent masters degree program in public health and journalism at the University of California, Berkeley.

      I am quoted in it.

      http://www.virology.ws/2016/01/07/trial-by-error-continued-did-the-pace-trial-really-prove-that-graded-exercise-is-safe/


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    5. On 2016 Aug 29, VINCENT RACANIELLO commented:

      Below is the text of a letter sent to The Lancet earlier this year, asking for an independent review of the PACE trial. The Lancet invited us to submit this letter, then rejected it for no reason. To keep the text within the limits of PubMedCommons, only the first six names of those who signed the letter are shown.

      Sir: The PACE trial reported that exercise and psychotherapy were effective treatments for chronic fatigue syndrome. Yet PACE was an unblinded study with subjective primary outcomes—a design already vulnerable to bias. As patients have long noted, PACE also suffered from additional methodological lapses likely to produce unreliable results. A recent investigation by David Tuller of the University of California, Berkeley, heightened public awareness of PACE’s flaws and sparked an open letter from us to The Lancet requesting an independent review.

      Among PACE’s serious missteps:

      *In a paradox, participants could—before treatment—already qualify as improved or “within the normal range” for fatigue and physical function, the primary outcomes. How? Because PACE’s “normal range” outcome scores actually allowed for worse health status than the eligibility scores required at entry to demonstrate serious disability. At entry, 13 percent of participants scored “within normal range” on one or both measures—details unreported in the paper. One PACE investigator described participants meeting these lax “normal ranges” as “back to normal”—a misleading statement highlighted in news coverage. An accompanying commentary, reviewed pre-publication by the PACE investigators, called this “a strict criterion for recovery.”

      *PACE claimed success based solely on subjective outcomes. Participants in one arm improved slightly on a walking test but remained severely disabled. The investigators subsequently dismissed this test and other objective measures--which all failed to demonstrate success--as irrelevant or non-objective. They describe their findings as robust, but unblinded trials with subjective endpoints, even without PACE’s many other problems, can only yield low-quality evidence.

      *PACE used one symptom to identify participants—six months of disabling, unexplained fatigue. A 2015 National Institutes of Health report recommended abandoning this broad definition because it generates heterogeneous samples that could “impair progress and cause harm.” PACE’s sub-group analyses of two alternate criteria are also difficult to interpret—an unknown number of patients might have met these criteria but been excluded by the initial definition and thus unobserved.

      *PACE significantly revised its protocol strategy for assessing primary measures and “recovery” criteria but did not include sensitivity analyses, the accepted method of evaluating the impact and dispelling concerns about bias. Whether or not investigators made revisions before reviewing outcome data is irrelevant: Outcome trends in unblinded trials are often apparent to trial leadership early on, even if assessors do not know treatment assignment. The investigators have declined to provide the protocol results and rebuffed data requests as “vexatious.”

      *A newsletter for participants--published while a third were still undergoing assessment-- included glowing testimonials from earlier participants about excellent outcomes but none reporting poor outcomes, potentially biasing subjective ratings toward the positive. The same newsletter reported that new U.K. treatment guidelines, “based on the best available evidence,” recommended the two PACE interventions favored by the investigators. Adaptive Pacing Therapy, an untested intervention developed specifically for PACE, was not mentioned.

      *Despite investigators’ explicit protocol promise to inform participants of “any possible conflicts of interest,” consent forms did not mention their ME/CFS-related work for disability insurers. It is irrelevant that they disclosed these conflicts in The Lancet and that insurers played no role in PACE. Given the omission, the signed consents are of questionable legitimacy.

      The investigators’ previous responses to such concerns have been unsatisfactory. We firmly believe the trial data should undergo a fully independent review.

      Vincent R. Racaniello, PhD Professor of Microbiology and Immunology Columbia University

      Ronald W. Davis, PhD Professor of Biochemistry and Genetics Stanford University

      Jonathan C.W. Edwards, MD Emeritus Professor of Medicine University College London

      Leonard A. Jason, PhD Professor of Psychology DePaul University

      Bruce Levin, PhD Professor of Biostatistics Columbia University

      Arthur L. Reingold, MD Professor of Epidemiology University of California, Berkeley


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