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.

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 definition¹ 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.

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

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.

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.

On 2014 Dec 10, Kath Wright commented:

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

On 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.

On 2015 Nov 13, Lydia Maniatis commented:

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

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.

On 2014 Oct 12, GianCarlo Panzica commented:

This article is free online at: http://dx.doi.org/10.13128/IJAE-8709

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

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."

On 2015 Jun 25, Paolo Sonego commented:

Broken link to the original paper.

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/.

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!

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

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?

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.

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.

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.

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

Many thanks,

Jessica Fleminger, Ben Goldacre*

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

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

On 2015 Feb 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

On 2014 Feb 21, Alexis Verger commented:

A short Pymol movie is available to visualize in 3D the protein's structure : http://www.youtube.com/watch?v=fxn1oKsV9iM

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.

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

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.

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.

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.

On 2013 Oct 31, John Cannell commented:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

70% of American toddlers do not take

On 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

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.

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

On 2014 Mar 12, Johnson Francis commented:

Any other recent trials on MRI conditional pacemakers?

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)

On 2014 Feb 04, Jan H. Duedal Rölfing commented:

Free full-text available: Danish version, English translation

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/.

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.

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.

On 2013 Dec 06, Lorraine Johnson commented:

It is not possible to keep up. Stepping back down the food chain a moment to RCTs. Consider the use of RCTs to solve combination regimen questions. Answer: cannot be done in our lifetime. We need better (and faster) tools. The summation of these efforts will necessarily incorporate the weaknesses of the underlying data to provide answers. See Saver re combination regimen RCTs and duration to answer.Saver JL, 2001 "Strategies for testing combination regimens include: head to head trials of all combinations, which lead to unwieldy trial numbers; very large multi-arm trials, which impractically delay interval information on regimen utility; and hierarchical, serial clinical trials. Systematic literature review revealed seven classes of agents already approved or in late phase III testing for preventing the development or slowing the progression of Alzheimer disease and five for ischemic stroke prevention. Possible combination regimens number 128 (2(7)) for Alzheimer disease and 32 (2(5)) for ischemic stroke. Hierarchical, serial clinical trials would permit identification of the optimum combination of these agent classes for Alzheimer disease through 127 trials, enrolling 63,500 patients, requiring 286 years; for ischemic stroke through 31 trials, enrolling 186,000 patients, requiring 155 years."

On 2013 Nov 13, Hilda Bastian commented:

Yes, that's an important point to keep in mind: this is just indicative of trends, not a way to find reviews that are rigorously systematic. The methods we used based on the Montori filter are detailed in the supporting information for the article here.

Filters are not the only way to identify systematic reviews via PubMed services. There is information on ways of finding curated systematic reviews at PubMed Health as well as via PubMed here. (Disclosure: I work on the PubMed Health project.)

On 2013 Nov 13, Amy Donahue commented:

I appreciate the appendix/supplemental data explaining how you counted/found systematic reviews. I do wonder about the quality of the SRs found using the Montori filter - as my colleagues and I (medical librarians) are asked more often to help with the searches for systematic reviews, we're finding that authors are calling many things "systematic" when they really aren't, and many journals don't hold SRs to the standards put out by the various organizations.

That aside, we are more than happy to help with the movement of prioritizing the creation of systematic reviews and our skills can be utilized in their creation. And 3 cheers for making sure they're accessible to both patients and clinicians!

On 2013 Nov 12, Hilda Bastian commented:

We haven't updated the data on trials yet, but will. Trials are subject to some different influences than systematic reviews, such as the impact in recent years of trial registration on the proportion of conducted trials being reported. Yes, the relationship between the two would be interesting to understand.

On 2013 Nov 11, Jamie Horder commented:

Thanks for this update. I wonder, has the number of primary trials published per day risen to the same extent?

My (wholly qualitative) impression is that the ratio of primary:metaanalysis publications has been falling in recent years; it would be interesting to find some evidence on that point.

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.)

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/.

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.

On 2014 May 04, Ivan Oransky commented:

This paper has been retracted: http://retractionwatch.com/2014/04/28/university-of-maryland-researchers-notch-second-retraction/

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.

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

Many thanks,

Jessica Fleminger, Ben Goldacre*

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

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

On 2015 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.”

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?

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.

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

On 2014 Dec 10, Kath Wright commented:

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

On 2013 Oct 31, John Cannell commented:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

70% of American toddlers do not take

On 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

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

On 2014 Dec 17, Sean Ekins commented:

slides on this work http://www.slideshare.net/ekinssean/collaborative-drug-discovery-a-platform-for-transforming-neglected-disease-rd-and-beyond

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.

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

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

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.

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.

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

On 2014 Apr 10, Alexander Klabnik commented:

I recommend

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

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

Many thanks,

Jessica Fleminger, Ben Goldacre*

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

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

On 2015 May 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."

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)

On 2014 Dec 10, Kath Wright commented:

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

On 2013 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/

On 2014 Dec 10, Kath Wright commented:

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

On 2014 Sep 07, Ivan Oransky commented:

This paper has been retracted, the second of Doo Ok Jang's papers to be retracted: http://retractionwatch.com/2014/09/03/structure-fumble-sinks-second-of-authors-jacs-papers/

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.

On 2017 Mar 05, Boris Barbour commented:

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

On 2015 Apr 25, James Tsung commented:

Link to corresponding ultrasound videos:<br> https://youtu.be/dPEAh2kuNyY?list=PLHg2xyua_KjtezNYwnO81hVNCS2HrjUi7

On 2014 Dec 17, Sean Ekins commented:

This work lead to the development of the open source fingerprints described here http://www.slideshare.net/ekinssean/new-target-prediction-and-vizualization-tools-incorporating-open-source-molecular-fingerprints-for-tb-mobile-version-2

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

On 2014 Dec 03, Harri Hemila commented:

A manuscript version is available at HDL

On 2014 Dec 17, Sean Ekins commented:

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

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.

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.)

On 2014 Dec 10, Kath Wright commented:

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

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

Many thanks,

Jessica Fleminger, Ben Goldacre*

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

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

On 2015 Jul 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.

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

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^-10 ). The random effect model shows similar values (O.R. = 1.67; 95% C.I. = 1.42, 1.98 ; P value = 1.2×10^-9 ).

On 2014 Mar 02, Zhongheng Zhang commented:

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

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

Many thanks,

Jessica Fleminger, Ben Goldacre*

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

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

On 2014 Mar 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.

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

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.

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

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

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

On 2014 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.

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.

On 2017 Mar 22, Misha Koksharov commented:

There are many interesting further comments: Dworak M, 2011

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

Many thanks,

Jessica Fleminger, Ben Goldacre*

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

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

On 2014 Apr 10, Alexander Klabnik commented:

I recommend

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/

On 2016 May 03, Suresh Panneerselvam commented:

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

On 2014 Dec 17, Sean Ekins commented:

slides on this work slides on this work http://www.slideshare.net/ekinssean/collaborative-drug-discovery-a-platform-for-transforming-neglected-disease-rd-and-beyond

On 2014 Dec 17, Sean Ekins commented:

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

On 2017 Mar 05, Boris Barbour commented:

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

On 2017 Mar 05, Boris Barbour commented:

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

On 2018 Jan 19, Natalie Clairoux commented:

Free version of this article available at http://hdl.handle.net/1866/19738

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

On 2016 Apr 08, Sergey Mitrofanov commented:

DOI: 10.1142/S0219720010004719 http://www.worldscientific.com/doi/abs/10.1142/S0219720010004719

On 2017 Mar 05, Boris Barbour commented:

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

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

Many thanks,

Jessica Fleminger, Ben Goldacre*

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

* 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