On 2015 Mar 31, James M Heilman commented:

Published an analysis of this paper here http://community.cochrane.org/news/blog/wikipedia’s-medical-content-really-90-wrong

Basically the data do not support the conclusions. It once again shows peer review is not infallible. But we already knew that.

On 2014 Oct 06, Paul Vaucher commented:

False conclusions drawn about the level of evidence of factual statements drawn from Wikipedia

Paul Vaucher, PhD, DiO^1, Jean Gabriel Jeannot, MD^2, Reto Auer, MD, MAS²

1 University Center of Legal Medicine Lausanne-Geneva, University Hospital of Lausanne (CHUV), Lausanne, Switzerland

2 Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland

We believe Hastly et al's study (Hasty RT, 2014) to be misleading and that their paper should not be made available to the scientific community without serious revision. Apparently, it has passed unnoticed that the methodology and statistical analysis they used had little to do with their stated hypothesis and that their interpretation of the statistics was erroneous. Authors concluded Wikipedia to be an unreliable source of health information when an alternate interpretation of the presented results would in contrary point towards considering Wikipedia as a trusted source of information, provided rigorous reanalysis and reinterpretation. There conclusions were therefore in contradiction with other studies on the subject (Archambault PM, 2013, Kräenbring J, 2014) that tend to show that for topics for which health workers contribute, such as for drugs, Wikipedia’s information as trustworthy as those from textbooks. These discrepancies can be explained by major statistical and methodological errors in Hastly et al’s publication.

The correct interpretation of the McNemar statistic suggests that the concordance for diabetes and back pain are significantly better than for concussion, and not the reverse, as stated by the authors. Using data provided in Table 3, for factual statements identified by both reviewers (two first columns of Table 3), for diabetes mellitus and back pain, the authors found that up to 94% of assertions on Wikipedia were verified (respectively 72 out of 75 statement and 63 out of 67, p<0.001 for NcNemar statistic). In contrast, for concussion, only 65% were verified (66 out of 98, p=0.888 for NcNemar statistic ). The McNemar statistic tests whether the proportion of factual statements from both reviewers, classified as concordant or discordant by the authors, are above what would be expected by chance alone (i.e. 50%). The interpretation for diabetes mellitus, if McNemar’s test should be used at all, is that we would fail to reject the null hypothesis of a proportion of concordance of 50% in < 1% of the cases. McNemar statistic thus suggests that the concordance for diabetes and back pain are significantly better than for concussion, and not the reverse, as stated by the authors. The calculation is based on the number of discordant results on the diagonals (i.e. 34 vs 1 for diabetes mellitus). It does by no means test the discordance between Wikipedia statements and existing guidelines. To test their hypothesis, it would appear more relevant to simply report the pooled average proportion of correct statements with their confidence intervals. On a technical note, McNemar statistic should not be used when there are different numbers of assertions assessed between reviewers. McNemar is also known to be highly dependent on the number of factual statements within each article. Article with higher number of statements would reach the level of significance with higher proportion of ungrounded factual statements.

Second, the article falsely leads readers to believe that all factual statements (assertions) from 10 Wikipedia articles were identified and independently assessed by two internist to see whether they were concordant or not. Using two reviewers is a recognized method for increasing precision of a measure. However, the authors did not to provide statistics allowing readers to assess the between-reviewers variability in the identification of assertions. Table 3 suggests that over a third of assertions were reported by only one of the two reviewers. Authors did not find a method to then resolve these dissimilarities (to use their definition in Table 2) and clearly define which assertions were factual statements and which were not. They then did not to define a method of agreement to define which assertions were supported by evidence and which were not. Analysed results therefore only tend to show that for certain topics, internists have difficulties in detecting factual statements from Wikipedia and knowing whether they are grounded or not.

Hastly et al’s findings suggest that while there might be some discrepancies in the quality of articles between topics, some appear of very high quality, such as diabetes mellitus and back pain. Given the unnoticed errors included in their article and the importance on the interpretation of the results, Hastly et al.’s published article reveals that peer reviewed misleading information can also be made available to the public.

Conflicts of interest : Reto Auer and Jean-Gabriel Jeannot are advocates of the use of Wikipedia as a communication mean to inform the population on health issues. Paul Vaucher is an important contributor to the French Wikipedia page dedicated to osteopathic medicine.

On 2014 May 28, Lane Rasberry commented:

I participate in WikiProject Medicine, the community which develops health content on English Wikipedia. We discuss most publications which review our content, but this paper for whatever reason was picked up by popular media.

Anyone who wishes to learn more about Wikipedia's health content is invited to say hello at WikiProject Medicine. There really is no way to understand Wikipedia without talking to some of the people who make it.

Here are some links to discussions about this paper:

+Poor paper on Wikipedia, the WikiProject Medicine discussion about this on 30 April

+r/science discussion May 27 on reddit, with 2000 comments

+Don’t Trust Wikipedia When It Comes to Your Health, Study Says, Time magazine

+Trust your doctor, not Wikipedia, say scientists, BBC

Online search will show 10 other news sources reviewing the paper. In my opinion journalists covering this academic article interpret it in various ways, none of which I would expect to be the interpretation which the authors would want people to have.

What a fascinating paper, and what an overwhelming public response to it!

On 2016 Mar 01, Jeffrey S Mogil commented:

In fact, stress is well known to produce both hypersensitivity to pain (see Imbe et al., Front. Biosci. 11:2179-2192, 2006) or inhibition of pain (see Butler & Finn, Prog. Neurobiol. 88:184-202, 2009), depending on the parameters of the stress. In our study, stress produced stress-induced analgesia. This is not a confound; it's the entire finding.

On 2016 Feb 22, Alireza Gharib commented:

Dear Editor I enjoyed studding your paper. However, I have a question. As an accepted fact “higher levels of stress induces pain”; yet, I suppose the results in this paper showed an inconsistent fact in support of other related literature “reduced pain response after stress exposure”. Maybe you just wanted to rule out stress as an intervening factor that may cause bias. I will be grateful if you could explain more. Best

On 2014 Nov 24, Guillaume Filion commented:

This article is one of the "CISCOM meta-analyses", which are very similar papers written by different authors. For more information about the CISCOM meta-analyses, check the blog post "A flurry of copycast on PubMed" at the following link http://blog.thegrandlocus.com/2014/10/a-flurry-of-copycats-on-pubmed

On 2017 Feb 24, Ahmet Selçuk Can commented:

Correction: Evaluation of leptin and insulin resistance in patients with cholelithiasis

We would like to correct our mistakes in the above paper¹ (Atamer A, 2013) titled “Evaluation of leptin and insulin resistance in patients with cholelithiasis” published in the Indian Journal of Biochemistry & Biophysics. We tried to contact the Editor of the Indian Journal of Biochemistry & Biophysics via e-mail on September 15th 2015 and via surface mail on February 16th 2016, but we did not get a response. The reason probably is that the Indian Journal of Biochemistry & Biophysics is not active and its last issue was published in April 2015, before our effort to contact the Editor. There are errors in the abstract, text and Table 1 of the manuscript. We apologize for these errors. These errors were also present in another publication of Atamer et al.² (Atamer A, 2014) that derived data from the same subject group. We were alerted by a correspondence by Agilli et al.³ (Agilli M, 2014) that pointed to these errors. Those errors were addressed and corrected in a previously published letter⁴ (Atamer A, 2016) submitted by us. We now address our mistakes in the above paper¹ (Atamer A, 2013). Table 1 has the following errors. The mean age of the controls was 56.93 years and was significantly higher than subjects with cholelithiasis (p=0.016). There was an error in the calculation of LDL by the Friedewald formula in healthy controls; the correct calculation of LDL-C is 100.86 mg/dl for the healthy control group. AST level for the healthy control group was 30.00 IU/L. AST level for the cholelithiasis group was 25.48 IU/L. The mean AST level of control subjects was significantly higher than subjects with cholelithiasis (p<0.001). The mean GGT level for the healthy control group was correct and was 41.70 IU/L, but the mean GGT level of cholelithiasis subjects was 35.81 IU/L. The mean GGT level of control subjects was significantly higher than subjects with cholelithiasis (p=0.002). The following corrections need to be done in the text of the manuscript that pertains to the erroneous Table 1. The third sentence of the Abstract should be “The control group included 25 women (62.5%) and 15 men (37.5%) with a mean age of 56.93 ± 11.73 yrs.” The first two sentences of the Results Section should be as follows: “There were 55 women (68.8%) and 25 men (31.3%) with a mean age and standard deviation (SD) of 50.56 ± 14.28 yrs in the cholelithiasis group and 25 women (62.5%) and 15 men (37.5%) with a mean age and SD of 56.93 ± 11.73 yrs in the control group. There were no significant differences in terms of BMI, fasting blood glucose, TG, CRP and ALT levels between two groups (p>0.05), but control subjects were older and had higher AST and GGT levels compared to cholelithiasis subjects (p<0.05).” Biochemical parameters and ultrasound studies subsection under Materials and Methods Section, Results Section, Table 1 and Table 2 should indicate that CRP was measured as highly sensitive CRP (hsCRP). An Acknowledgements section should be added and should mention that part of the data was submitted to a different journal² Atamer A, 2014 and acknowledge the editing and submission assistance by Ahmet Selçuk Can (the third author of this letter). Aytaç Atamer and Yıldız Atamer are responsible from the integrity of the published data^1,2 Atamer A, 2013, Atamer A, 2014. Ahmet Selçuk Can is responsible from editing and submission of the previously published manuscripts^1,2 Atamer A, 2013, Atamer A, 2014 and writing and submission of this correspondence. We concur with Agilli et al.³ Agilli M, 2014 and accept that several errors make the previously published studies^1,2 Atamer A, 2013, Atamer A, 2014 unreliable⁴ Atamer A, 2016.

Aytaç Atamer^1,2 , Yıldız Atamer¹ and Ahmet Selçuk Can^1*

¹ Termal Vocational School, Yalova University, Kışla Caddesi, Gökçedere Mahallesi, Nergis Sokak, No: 23, Termal, Yalova, 77200, Turkey

² Formerly from the Division of Gastroenterology, Department of Internal Medicine, Republic of Turkey, Ministry of Health Haydarpaşa Numune Training and Research Hospital, Istanbul, Turkey

*Corresponding Author E-mail: selcukcan@endokrinoloji.com

References

1) Atamer A, Ovunc AO, Yesil A, Atamer Y. Evaluation of leptin and insulin resistance in patients with cholelithiasis. Indian J Biochem Biophys 2013;50:266-72.

2) Atamer A, Kurdas-Ovunc AO, Yesil A, Atamer Y. Evaluation of paraoxonase, malondialdehyde, and lipoprotein levels in patients with asymptomatic cholelithiasis. Saudi J Gastroenterol 2014;20:66-73.

3) Agilli M, Aydin FN, Aydin I. Serum paraoxonase and malondialdehyde levels in asymptomatic cholelithiasis. Saudi J Gastroenterol 2014;20:203-4.

4) Atamer A, Atamer Y, Can AS. Response to: Serum paraoxonase and malondialdehyde levels in asymptomatic cholelithiasis. Saudi J Gastroenterol 2016;22:84-5.

On 2015 Jan 21, John Cannell commented:

How was the abuse "documented"? By a Child Abuse Committee? By Child Protective Services (CPS)? By the courts? How were the caregivers judged to be guilty? Without witnessed abuse or free and un-coerced confessions by caregivers, you have no way of knowing how many innocent caregivers were included in the "guilty" group.

Therefore, selection bias makes studies similar to Darling et al's practically useless. What percent of studies of “guilty” cases involve CPS telling innocent parents if they admit to the abuse - and take parenting classes - they can immediately get their infant back and avoid further costly litigation? What percentage of “guilty” cases involves CPS allowing innocent parents to plead "guilty" to the lesser charge of neglect to get their infant returned and avoid further litigation?

In what percentage of “guilty” cases does the district attorney or CPS give a mother the “Sophie’s Choice” of not being prosecuted and getting her infant back if she will testify against her innocent husband? What percent of “guilty” cases involve an innocent parent accepting a plea bargain after the defense attorney concludes a trial will result in conviction?

For these reasons studies on infantile child abuse such as Darling et al have selection bias and, in my opinion, include an unknown number of innocent caregivers in the "guilty" group, making the studies scientifically unreliable.

On 2014 May 07, James C Coyne commented:

Nice ruling out of one possible bias in using community-based data to estimate effectiveness of flu vaccine effectiveness.

On 2014 Aug 20, Nikolai Slavov commented:

Q&A about this paper: http://crosstalk.cell.com/blog/veries-lie-hidden-behind-the-facade-of-popular-assumptions-qa-with-nikolai-slavov

On 2014 Apr 29, Gwinyai Masukume commented:

“Data from WHO [World Health Organization] suggest that nearly half of all births in China were delivered by caesarean section in 2007–08 …”; in the article that the author’s cite to support their statement it is written, “The results, especially rates of caesarean section, should not be regarded as representative rates and outcomes for entire countries or regions.” [1]

The authors claim that the caesarean section rate in China (42% in 2010) is the highest in the world; however this does not seem true; the Chinese rate could be around 26% (still a high rate) but the rate is certainly not the highest in the world [2].

The authors also state that WHO recommends a 15% proportion of births by caesarean section, but they give no reference. WHO states, “Both very low and very high rates of caesarean section can be dangerous, but the optimum rate is unknown.” - the 15% proportion has its origins in 1985 [3].

References

[1] Lumbiganon P, Laopaiboon M, Gülmezoglu AM, Souza JP, Taneepanichskul S, Ruyan P, et al. Method of delivery and pregnancy outcomes in Asia: the WHO global survey on maternal and perinatal health 2007-08. Lancet. 2010; 375(9713):490-9. Lumbiganon P, 2010

[2] Gibbons L, Belizán JM, Lauer JA, Betrán AP, Merialdi M, Althabe F. The Global Numbers and Costs of Additionally Needed and Unnecessary Caesarean Sections Performed per Year: Overuse as a Barrier to Universal Coverage. World Health Report, Background Paper, 30. [Internet] 2010. [cited 25 April 2014]. Available from: http://www.who.int/healthsystems/topics/financing/healthreport/30C-sectioncosts.pdf

[3] Monitoring emergency obstetric care – a handbook. [Internet] 2009. [cited 25 April 2014]. Available from: http://whqlibdoc.who.int/publications/2009/9789241547734_eng.pdf

On 2016 Aug 24, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT00123456. We believe the correct ID, which we have found by hand searching, is NCT00403767.

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

Many thanks,

Jessica Fleminger, Ben Goldacre*

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

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

On 2016 Aug 30, 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 NCT001747. We have contacted the corresponding author, who has told us that this trial was not registered.

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 Aug 16, Melissa A Farmer commented:

Dear Dennis,

Thank you for your interest in our methods, and we are pleased to address your questions.

The first question raised is related to the amount of solution injected. For estradiol and progesterone, the mice received injections of 0.1 mL of each solution under the scruff of the neck. We found that the mice could easily tolerate this volume (no scratching or visual discomfort), provided that injections were limited to once per week (thereby limiting frequency of mating). We chose this volume due to the sensitivity of our scale, which constrained the concentration of stock solutions we could make. Lesser volumes with appropriately adjusted dilutions would work, as well.

The second issue is related to optimizing copulation/female receptivity in novel couples. On one hand, the probability of a novel couple mating can be enhanced by providing the male with prior sexual experience with other receptive females (“stimulus” females). This prior learning will increase the frequency with which he approaches the novel female, which in turn increases probability that copulation will occur.

A complementary strategy is to optimize hormonal and environmental factors that can facilitate female receptivity in virgin mice, independent of the actions of the male. Sexually mature female mice should be used (> 6 weeks age). Based on our experience, the timing of the progesterone injection is the most important factor that optimizes a female’s behavioral response during testing. Unfortunately the mouse mating literature is older and authors infrequently reported the timing of progesterone administration in females (hence the Jones et al. reference). In pilot experiments, we varied progesterone injections from 4-6 hours pre-test, and in our hands, 5.5 hours produced the most consistent behavioral results. To further optimize behavioral receptivity, we scheduled testing towards the beginning of the dark cycle when mice would be most physically active. Even though mice were maintained in an artificially-lit vivarium, we noticed seasonal variation in the onset of dark cycle physical activity, and so we shifted the timing of testing (and therefore progesterone injections) accordingly, with a later testing time during winter. Also note that more complicated mating environments, like a paced mating boxes, require repeated habituation to reduce novelty effects.

On 2014 Aug 14, Dennis Eckmeier commented:

Dear authors,

A really interesting paper!

I have a question according to methods:

You write "Sexual receptivity was induced in ovariectomized females with subcutaneous (s.c.) injections of estradiol benzoate (5 μg/0.1 ml in sesame oil; Sigma-Aldrich) given 48 h pretest, and progesterone (500 μg/0.1 ml in sesame oil) 5.5 h pretest. These parameters are known to induce a state of optimal sexual receptivity, comparable to the estrus phase (Jones et al., 2013)."

What amount of drug solutions did you administer?

You determined that some pairs of treated ovariectomized females and males would indeed mate, so no doubt it worked for your study. However, a study I am planning doesn't allow previous encounters between the stimulus female and the male. The paper you cite (Jones et al., 2013) is about rats. Did you somehow determine whether your treatment induces optimal sexual receptivity in mice?

On 2014 Apr 28, Jim Woodgett commented:

SB415286 inhibits both the GSK-3alpha and GSK-3beta isoforms (encoded by different genes) with similar potency. Beta-catenin is only stabilized when Axin-associated GSK-3 (a mixture of both alpha and beta isoforms) is disrupted following Wnt receptor binding - causing association with of Axin with LRP5/6 (PMID 22682247). Knocking out GSK-3 alpha or GSK-3beta typically has no measurable effect on beta-catenin levels as only 5-10% of cellular GSK-3 is bound to Axin and each isoform fully compensates for the other in this pathway (e.g. PMID 17543867). Hence, the observed effects are likely (in the case of the drug) not GSK-3beta specific and in the case of the KO, likely reflect increased sensitivity of the residual GSK-3alpha to an endogenous signal (presumably Wnt).

On 2015 Feb 09, Edoardo Aromataris commented:

Thank you for your comment Wichor and for pointing this out for readers. You've highlighted how a simple detail in a search strategy and familiarization with the search platforms used can increase the specificity of the search markedly.

On 2015 Jan 29, Wichor Bramer commented:

I found a rather lage error in the search strategy as presented in this article, resulting in the retrieval of 26 times more irrelevant than relevant terms. When creating a complex search strategy it is very important to have the parentheses correct. The authors developed a search strategy in which they plan to search for P AND (I OR C) AND O, which is a god way (albeit maybe a bit too much elements). However the search string as shown on page 53 is constructed as (P) AND (I) OR (C) AND (O). PubMed alike other databases does not have a preset preference for Boolean operators, but just adds new elements in the order given. Constructed like this PubMed will retrieve all articles on Music Therapy and the desired outcomes, but not related to dementia. When using this search strategy in PubMed it currently retrieves 8000 references. When the parentheses are corrected only 300 articles remain, containing much more relevant references. Do watch closely when creating more complex searches that parentheses are placed correctly. Always fill them in yourself, and don't let PubMed decide that!

On 2014 Apr 28, Daniel Macqueen commented:

Firstly, congratulations to these authors for being the first to publish a salmonid genome sequence. This is a major achievement and an important landmark for salmonid biologists and fish biologists generally. I find many of the analyses in the paper to be interesting and novel.

With that said, readers of this paper should be aware that the timing of the salmonid genome duplication (i.e. ‘Ss4r’) was already demonstrated in an earlier article that (surprisingly) was not cited by Berthelot et al. (Macqueen and Johnston 2014. A well-constrained estimate for the timing of the salmonid whole genome duplication reveals major decoupling from species diversification. Proc. R. Soc. B. 281: 20132881). See Macqueen and Johnston's earlier paper here http://rspb.royalsocietypublishing.org/content/281/1778/20132881.short?rss=1

In short, Macqueen and Johnston (2014) performed a Bayesian relaxed molecular clock and phylogenetic analysis, calibrated by the fossil record, to estimate that Ss4r occurred 88-103 Mya. The Berthelot et al. estimate (90-102 Mya) was achieved using a more basic method, but nevertheless, is strikingly consistent with our earlier independent result.

I would also like to comment on some text from Berthelot et al:

“We first use the rainbow trout genome to refine the timing of the Ss4R and we dated this event around 96 Mya (±5.5 Mya), a timing in the upper range of the previous 25–100 Mya estimation^{11^.} This result is in striking contrast with the age of the Salmonidae family, which has been estimated as 50–60 Mya ^{4,16^,} suggesting that the Ss4R occurred long before the last common ancestor of extant salmonids.”

Again, Macqueen and Johnston (2014) reported this result already. From the abstract: “Our results suggest that the event [WGD] occurred no later in time than 88 Ma and that 40–50 Myr passed subsequently until the [salmonid] subfamilies diverged”.

These comments were made by Dr Dan Macqueen from the Institute of Biological and Environmental Sciences, University of Aberdeen, United Kingdom. Email: daniel.macqueen@abdn.ac.uk

On 2014 Nov 23, Stephen Wood commented:

We feel the authors should consider the possibility that their key finding, that Large for Gestational Age (LGA) birth weight is a risk factor for stillbirth, was an artifact of sampling. We note that 50% of the stillbirths in your study occurred at <28 weeks gestation yet < 1% of the live birth controls were <28 weeks and only 1% <32 weeks. This may have been appropriate for the analysis that determined LGA using population norms but error may have been introduced when using the ultrasound (Hadlock) or indvidualized norms. In developing these norms Hadlock et al assessed only 392 subjects and although they had ultrasounds at a range of gestational ages the accuracy of the estimates was only reported for deliveries > 36 weeks. Therefore, it is uncertain how accurate they would be for preterm fetuses. The individualized norms are also prone to similar error as they are as essentially slightly adjusted Hadlock ultrasound norms. As your controls were a population based sample not matched by gestational age then this error could have been important. To investigate this possibility we analyzed data from our provincial perinatal database. For the years 1992-2009 there were 727693 singleton births at 23 weeks or greater gestation, we excluded 11 with gestational age>45 weeks and 3216 with missing birth weights. In the first analysis all stillbirths were matched with the next two live births (population based controls). The gestational age distribution of live birth controls was similar to your study with only 1.1% delivering <28 weeks. Using the same population norms as your study (Alexander) we observed similar results to those you reported; SGA was associated with stillbirth using both population and ultrasound norms but LGA only increased the risk of stillbirth using the Hadlock ultrasound norms. In fact using the population norms it was protective.

Hadlock U/S norms SGA (small for gestational age) OR 6.38 (5.77, 7.06) AGA (appropriate for gestational age) Reference LGA (large for gestational age) OR 1.91 (1.64, 2.22)

Alexander Population norms SGA OR 6.43 (5.74, 7.21) AGA Reference LGA OR 0.61 (0.51, 0.74)

To evaluate the possible effect of sampling we then matched all stillbirths to the next two live births with the same gestational age.

Hadlock (ultrasound norms) SGA OR 4.77 (4.32, 5.26) AGA Reference LGA OR 0.98 (0.85, 1.13)

Alexander (population norms) SGA OR 6.47 (5.78, 7.24) AGA Reference LGA OR 0.83 (0.69, 1.01)

The results as you see are quite different. While SGA is still strongly associated with stillbirth LGA is not using either population or ultrasound norms. This suggests that the increase in risk of LGA observed in your study was an artifact of sampling. This almost certainly applies to the results using the "individualized norms" as they essentially modification of the ultrasound norms. We suggest that you do a similar analysis on your own data with gestational age matched controls to ensure the increase risk of stillbirth you observed with LGA is robust to changes in the control population.

On 2015 Jan 07, Wichor Bramer commented:

Volpato et al investigated in their article what the best method is to search phrases in the database PubMed. Does it matter whether parentheses, quotes or truncation are used? They could have saved themselves time and FAPESP money, because the answer to that can easily be found in NLM documentation, or by attending an advanced PubMed class. Parentheses are necessary only when combining OR's and AND's. Around phrases they do not change anything to the results. Quotes around phrases create an exact search for that phrase, while phrases without quotes will be split in parts combined with AND. Ending a phrase with an asterisk (truncation) will search for any phrase that starts with that phrase. In general most results will be found not using quotes or truncation (but this might contain much noise), followed by truncated phrases, and the least of quoted phrases. (It would be interesting to see the four queries in which quotes retrieved more hits). Therefor Volpato et al conclude in the text that no quotes should be used. However they state that quotes are recommended when the searcher wants to be exact (that is indeed the case, the search will be more exact) and they explicitely do not recommend using truncation, since it reduces the number of hits. But had they compared truncation to quoted phrases they would have found that truncated phrases generate more hits than untruncated phrases (cardiac event OR cardiac events), at least when applied well (in their example they should have used intracapsular partial tonsillectom*, to also find the intracapsular partial tonsillectomies). Whether or not the simple search or the search history tool should be used completely depends on the searcher. If it does not make a difference in the results, one can not draw a conclusion to that, and one should not recommend one or the other. A good systematic search, however, combines truncated phrases and mesh terms and is optimized to find as much relevant articles as possible.

On 2014 Apr 29, Amanda Capes-Davis commented:

Unfortunately KB cells do not come from oral squamous cell carcinoma. KB was shown to be cross-contaminated by Stanley Gartler in 1967; these cells are HeLa, from cervical carcinoma. For a database of cross-contaminated or otherwise misidentified cell lines, see http://iclac.org/databases/cross-contaminations/.

On 2014 May 13, MARTA MARGETA commented:

For the authors' reply, see: Reply to Deighton et al.: Neuronal activity regulates distinct antioxidant pathways in neurons and astrocytes.

On 2014 Apr 30, Andreas R Gruber commented:

The idea that the G/U repeat in C/D box scaRNAs might serve as an import signal into Cajal bodies was first proposed here:

Insights into snoRNA biogenesis and processing from PAR-CLIP of snoRNA core proteins and small RNA sequencing. Kishore S1, Gruber AR, Jedlinski DJ, Syed AP, Jorjani H, Zavolan M. Genome Biol. 2013 14(5):R45. PMID: 23706177

I am happy to see that there is now also experimental evidence supporting it!

On 2016 May 07, Jan Preiss commented:

I was a little bit surprised to see that the NBI mode in the study by Leung et al. an endoscope from the 190 series was compared to the white light mode in an endoscope from the 260 series. Having worked with both types of endoscopes I find even the white light picture in the 190 series a lot sharper and brighter than any of the older Olympus endoscopes - including the 260/160 series. It is very difficult to conclude from this design whether the higher adenoma detection rate actually stems from using the NBI mode or merely from using an endoscope with superior light and optics.

On 2014 May 14, Thein Oo commented:

I am the author of this manuscript. I do not think the citation sequence of the author's name is correct. It should have been "Oo TH" instead of "Hlaing Oo T" as my last name is "Oo". "Hlaing" is my middle name.

On 2014 Jun 17, Patrick Mc Gann commented:

It is not "technically" wrong, it is plain wrong!

On 2014 May 21, Maria João Carvalho commented:

The paper approaches the way how information spreads can lead to wrong actions, knowledge etc., so it should have been more accurate. I agree that the paper is itself Science miscommunication!

On 2014 May 06, D. Hilbert commented:

NDM-1 is not a microbe. It is an enzyme produced by certain microbes. Even if it has erroneously been referred to as a "superbug, bacterium, enzyme and virus" in the popular press there is no reason why it should be referred to as such in a peer-reviewed scientific publication. This article clearly should not have been published and should not be indexed in PubMed with a factually incorrect title and abstract.

On 2014 May 02, Alicia Mason commented:

The NDM-1 microbe has been referred to as a superbug, bacterium, enzyme, and virus interchangeably in popular, trade, professional and social media. As this article’s focus is on how NDM-1 has been portrayed in the popular press, referring to it as a virus fits with the nomenclature that had been used in the popular media at that time. Whilst acknowledging that referring to NDM-1 in this way is technically wrong, the editors of Journal of Health Communication are confident that the essence of what is covered in the article and quality of the peer review have not been compromised.

On 2014 Apr 25, Maneesh Paul-Satyaseela commented:

NDM-1 is not a virus, but an enzyme produced by bacteria. Indexing of this article could cause public confusion...

On 2014 Apr 23, Allison Stelling commented:

Journal of Health Communication seems to be one of the partial open access ones (see http://www.tandfonline.com/page/openaccess/openselect)- may be more about "proliferation" than "open access".

On 2014 Apr 23, Patrick Mc Gann commented:

How was this ever allowed to be published? NDM-1 is NOT a virus! I cannot believe that this paper underwent any sort of peer review, but if it did, this is terrible! The Journal of Health Communication needs to do some explaining! The proliferation of these open access journals is becoming a serious problem for scientific integrity.

On 2014 Apr 22, Vasily Aushev commented:

assigning the name which is already commonly used for the protein (RalA is small GTPase) is not very good idea.

On 2014 Sep 17, Asht Mishra commented:

A correction to this article has been published online. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133402/

On 2014 Aug 27, Ryan Radecki commented:

Post-publication commentary:

"The BATiC Score for Pediatric Trauma – Promising, But Not Prime-Time"

Excluding significant intra-abdominal trauma on the basis of clinical evaluation is a lost art in the realm of zero-miss. Nowhere is this more important than in a pediatric population, considering the small, but real, potential from harms due to exposure to ionizing radiation from CT.

This is the Blunt Abdominal Trauma in Children (BATiC) score, derived in 2009 by a Swiss group....

http://www.emlitofnote.com/2014/08/the-batic-score-for-pediatric-trauma.html

On 2014 Apr 26, Anders von Heijne commented:

This is a really good review about PRES. Let me just add yet another possible mimicker - inflammatory CAA; with oedema, microhemorhages and areas with restricted diffusion.

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 NCT00137744. We believe the correct ID, which we have found by hand searching, is NCT00133744.

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 2017 Mar 14, Ricardo Belda commented:

Very interesting!

On 2014 May 30, Lane Rasberry commented:

The author says, "This study is unique in that it is the first scientific investigation, to the authors' knowledge, into the harnessing of Wikipedia usage data over time to estimate the burden of disease in a population." Yes, this is unique, and the Wikipedia community struggles to manage responsibility for what to do with the tremendous amount of traffic data the site creates. As the paper says, WP:STATISTICS is a description on Wikipedia of all the traffic on Wikipedia. A lot of privacy issues are still being sorted, but the community intent has always been to make as much information as ethically possible available to researchers.

It is encouraging to the community of Wikipedia editors to see a study like this because it confirms that when sources like Wikipedia make health information available to the public, then the public will spontaneously seek the same when the need arises and presumably use the information to inform the health decisions they make. It is more encouraging to think that this study was made possible because of Wikipedia's odd practice of making lots of visitor data available; of course commercial websites can never do this, but the public space of Wikipedia allows for novel research like this study.

This study sets precedent beyond the conclusions made from the research - in the Wikipedia community it has provoked discussion about the role of Wikipedia in serving public health.

On 2014 Aug 30, Michelle Lin commented:

An interesting perspective on the MMI for medical students, applying to an EM residency program. A week-long ALiEM-Annals of EM discussion can be seen here, along with a videocast with the authors and experts.

http://www.aliem.com/multiple-mini-interviews-annals-em-resident-perspective-article/

On 2015 Apr 11, Gerhard Nebe-von-Caron commented:

in the absence of the raw dada to be available at the flow repository it is not possible to evaluate the validity of the data and their analysis. Whilst the supplementary data show 4 dot plots of side scatter versus fluorescence, neither the the data of the reference particles on which the gating was established is shown, nor the ungated data against trigger level.

On 2014 Jun 06, Pedro Reche commented:

Based on the success of this Special Issue, we have been invited to make it into an Annual Special Issue. Call for papers for the 2015 edition is at http://www.hindawi.com/journals/jir/si/768102/cfp/.

On 2016 Nov 22, MICHAEL BALLARD commented:

This manuscript has been republished as Li, W., et al. (2014). “Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer's disease mouse model.” Mol Brain 7(1): 65. See PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172865/ and journal site: https://molecularbrain.biomedcentral.com/articles/10.1186/s13041-014-0065-y

Figures 4 and 5D from the original article have been removed from the republished version.

According to the authors' retraction notice: “This article described the effects of elevating brain magnesium on preventing and reversing cognitive deficits in an Alzheimer's disease mouse model. During recent efforts to extend this work, we discovered errors in the quantification of the expression and/or phosphorylation of a subset of signaling pathways, particularly related to Figures 4 and 5D. Despite these errors, the major conclusions of the paper remain substantiated."

On 2014 Nov 25, Hugo Spiers commented:

See F1000 commentary on this article: http://f1000.com/prime/718354176

On 2014 Apr 26, Sergio Stagnaro commented:

None

On 2014 Apr 25, Anders von Heijne commented:

Yes, we need a discussion that is practically useful in the clinical environment. There are so many areas of medical knowledge where RCTs are more or less impossible to perform. Focusing on available evidence rather than methodology seems to be a useful framework. Medical practice is at times a difficult intellectual challenge and we need all the help we can get in order to move from data on group level to relevant information that can help the individual patient - from Aristotles episteme and theoria to phronesis and praxis .

On 2014 May 21, Emran Askari commented:

The Global Occurrence of VRSA as a Serious Public Health Concern

Zulfiqar Ali Mirani¹ , Emran Askari² , Zahra Moravvej²

¹ Microbiological Analytical Centre, PCSIR Laboratories Complex, Karachi ² Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

In their study, Rossi et al (Apr. 17 issue) [Rossi F, 2014] describe the presence of community-associated MRSA containing vanA as a serious public health concern. In such a comprehensive study, the authors should have considered a previous similar report of VRSA. Our report described the strain, CP2 which was isolated from the blood sample of a post-operative cardiac patient in Pakistan [Mirani ZA, 2013]. Similar to the study of Rossi et al, CP2 was also able to transfer vancomycin resistance trait to other staphylococci. It contained a Tn1546-like element without open reading frame 1 and an insertion sequence element similar to IS1216V [Mirani ZA, 2013]. Further studies showed that the strain belongs to agr type II and carries SCCmec type IV which is prevalent in community-associated MRSA (unpublished data).

The number of VRSA incidences has been the subject of our recent discussion [Moravvej Z, 2013]. Furthermore, considering the new VRSA reports from Portugal [Melo-Cristino J, 2013] and Brazil [Rossi F, 2014], it has now been reported from four continents. This warrants the need for continual monitoring of VRSA in order to predict the global occurrence of the “perfect storm” [Tenover FC, 2008].

On 2014 Apr 23, Hilda Bastian commented:

This is a critical topic for a systematic review, given the potential for decision-making interventions to increase inequality in the community. The conclusions here seem to me over-optimistic. There's another way of putting this: the meta-analyses for most outcomes found no improvement. The weight of evidence for improvement was carried by less than a handful of studies - including some intensive interventions such as community outreach strategy (Wray RJ, 2011).

It's striking that with so much research in this field, such a small proportion could be found that addresses such a critical question. The results here certainly point to the importance of doing more work on this subject, because the cause clearly is not hopeless. Beyond these studies, though, lies another critical question: who is adopting these practices in the community, and is it contributing to a lessening or increase in inequity? Generally, only concerted effort can prevent those who already have more, getting more - in this case, information and clinicians' time (Bastian H, 2003).

On 2016 Sep 11, Morten Oksvold commented:

Before reading or citing this article, please read the conclusion from the misconduct investigation regarding this article:

http://www.sciencemag.org/news/2016/09/panel-finds-misconduct-rat-paper-star-surgeon-paolo-macchiarini

Report regarding the Macchiarini case:

http://ki.se/sites/default/files/karolinska_institutet_and_the_macchiarini_case_summary_in_english_and_swedish.pdf

On 2016 Sep 10, Md. Shahidul Islam commented:

Please note the information posted by the Karolinska Institutet where the experiments reported in this paper were conducted. Click here

On 2017 Oct 24, Victoria MacBean commented:

Plain English summary

With a rise in obesity, a bigger effort must be made to understand all the factors and effects of obesity on the human body. It is already known that obesity is associated with an increase in work of breathing and neural respiratory drive (the muscular effort required to breathe), as well as changes in lung capacities. It can also cause hypercapnic respiratory failure which is when there’s too much carbon dioxide in the blood. However, the effects on the mechanics of breathing are unclear. This study attempts to measure the effect of obesity on lung volume and various pressures in the chest and better understand the physiological differences between different weight people.

9 obese people and 9 normal weight people volunteered to be measured whilst seated and whilst lying on their back. During the study, the subjects breathed into the mouthpiece of a machine called a spirometer which monitors the speed and volume of air movement into and out of the lungs. Pressures in the chest and abdomen were also measured, along with the amount of air remaining in the lungs after a breath out (functional residual capacity, or FRC).

After evaluating results, it was noted that high pressures in the chest are have an important role in the mechanisms of the respiratory system. The chest and abdomen pressures were found to be much higher in the obese group, and the FRC lower. The strength of the breathing muscles were measured and the result showed that the obese group had weaker muscles. There was a direct relationship seen between subjects’ waist circumference and the chest and abdominal pressures, as well as with the drop in FRC.

One of the main conclusions is that gastric and oesophageal pressures correlated with waist size, since the obese group had significantly higher pressures. One can deduce from this result that these high pressures are inhibiting efficient function of the lungs, and contributing to the reduced volume of air in the lungs. To bring this research into practical everyday healthcare, more could be done to attempt to reduce abdominal pressures in obese patients. By doing so with appropriate treatment in the future, obese people may be able to reach normal lung function, thereby reducing the number of patients suffering from breathlessness and sleeping disorders from respiratory problems.

This summary was produced by Casril Liebert, Year 13 student from JFS School, Harrow, London as part of the authors' departmental educational outreach programme.

On 2014 Jun 21, Christopher Southan commented:

It is surprising that phraseology such as "chemical features of the qi-enriching and blood-tonifying compounds" was considered appropriate for a cheminformatics scientific report

On 2014 Aug 28, Guillem Feixas commented:

A los lectores hispanohablantes les recomiendo visionar un video relacionado con este artículo. Se trata de la conferencia impartida el 28-19-2013 por el Prof. Guillem Feixas titulada "Conflictos cognitivos, salud mental y psicoterapia: Un enfoque constructivista" en la Facultad de Psicologia de la UNED, en Madrid. Se puede ver completa (2h. y 14 min.) incluyendo presentación por parte del Sr. Decano y la Prof. Begoña Rojí, y también con un amplio turno de preguntas y respuestas. http://www.canal.uned.es/mmobj/index/id/15596

On 2014 Aug 28, Guillem Feixas commented:

Interested readers can watch a vídeo much realted to this paper. It was a keynote address of Dr. Guillem Feixas titled "Cognitive conflicts: A neglected issue in CBT?" given at the 42nd. Annual Congress of the European Association for Behavioural and Cognitive Therapies (Geneva, 1st. of sept. 2012) http://youtu.be/Fz631j71r3o

On 2014 May 09, Greg Lennon commented:

This article is certainly worthy of discussion, not just due to the credibility and experience of its authors, but I hope that future publications will be able to provide some benchmarking and analysis of systems outside the US in terms of the aspects that are better (or not) compared to the current American system, and to provide context for the proposals in this publication.

On 2014 May 06, Melissa Vaught commented:

In this perspective, Alberts et al reference a white paper published by the American Society for Biochemistry & Molecular Biology (ASBMB), Toward a Sustainable Biomedical Research Enterprise. In part, the white paper provided a basis for a discussion hosted by the ASBMB Public Affairs Advocacy Committee at Experimental Biology 2014. My report from the session provides a summary and includes a link to a collection of tweets posted by myself and others from the session.

Both Jeremy Berg (president of ASBMB) and Paula Stephan (a professor of economics) highlighted the pronounced increase in PhD production in recent years. Alberts et al state here, "The goal of the next set of recommendations is to gradually reduce the number of entrants into PhD training in biomedical science—producing a better alignment between the number of entrants and their future opportunities..." The message from these groups seems clear: In biomedical sciences, the influx of funds was met by expansion of PhD programs, and it's now time to scale back PhD production. Yet in this and another session, I heard some faculty push back against the idea that their departments should train fewer PhD students. This dissonance emphasizes the importance of a question raised by the ASBMB white paper: "Are there approaches that could estimate how many Ph.D.-, M.S.-, and B.S.-level scientists are needed for the American biomedical research enterprise?"

Finally, I would like to raise an issue that I have missed in the discussions thus far. Diversity of the biomedical workforce is also out of balance (see, for example NSF data on Women, Minorities, and Persons with Disabilities in Science & Engineering). I think it's important to consider how proposed changes might disproportionately affect underrepresented minorities and how to ensure that we continue to improve diversity in science while moving toward a sustainable research enterprise.

On 2014 Aug 14, Jim Woodgett commented:

While Alberts et al. describe the situation in the USA, they might take a look to their north where the equivalent funding agency to NIH (except with a 30th of the budget), the Canadian Institutes of Health Research, is grappling with several of the issues raised by the authors. The "funding reforms" are documented here (http://www.cihr-irsc.gc.ca/e/44761.html) and attempt to address a slow but steady decline (slow train wreck) in confidence in adjudication caused by a 6 year flat-lined budget further exacerbated by the predictable reactions of scientists to the increased pressures.

Some of their proposed changes are interesting (virtual review, 7 year programs, etc.) but it's a huge simultaneous experiment with no controls, transitional funding or Plan B. I encourage researchers in other jurisdictions to follow the progression of the CIHR reforms and to learn from their outcomes. Clearly the current ecosystem of science is not sustainable without either additional investment or elimination of some of the perverse incentives that drive poor decisions and planning.

On 2014 Aug 14, David Colquhoun commented:

I think that the problems are stated very well in this article. See also 'The Mismeasurement of Science' (http://www.dcscience.net/?p=186 ), and other writing by Peter Lawrence of the Lab for Molecular Biology. But the solutions that are suggested are not as convincing as the statement of the problem. I fear that Alberts at al. have failed to grasp the nettle. My suggestions are as follows(based on 'Open access, peer review, grants and other academic conundrums': http://www.dcscience.net/?p=487 ) .

(1) Limit the number of papers that an individual can publish. This would increase quality, it would reduce the impossible load on peer reviewers and it would reduce costs. It would also encourage the best people to do experiments themselves, rather than presiding over an army serfs.

(2) Limit the size of labs so that more small groups are encouraged. This would increase both quality and value for money.

(3) More (and so smaller) grants are essential for innovation and productivity.

(4)Move towards self-publishing on the web so the cost of publishing becomes very low rather than the present extortionate costs. It would also mean that negative results could be published easily and that methods could be described in proper detail.

(5) Peer-review is less than satisfactory even for the most glamorous journals. At the bottom end of the market it is utterly ineffective. The solution to that is open post-publication peer review. Every paper should be followed by a comments section.

(6)Stop using metrics as a substitute for reading papers. The use of metrics is corrupting science. Citation counting is inadequate (see http://www.dcscience.net/?p=182 ). Altmetrics are plain silly (http://www.dcscience.net/?p=6369 ).

On 2014 Apr 28, Kenneth D Gibbs commented:

The potential, downward impacts of the current system are real. In speaking to recent biomedical science Ph.D. graduates, issues with science funding generally, and the climate created by the current funding climate particularly, came up as reasons for some to leave academic science and/or science altogether. I commend my recent work published in CBE Life Science Education: "What Do I Want to Be with My PhD? The Roles of Personal Values and Structural Dynamics in Shaping the Career Interests of Recent Biomedical Science PhD Graduates". The link is here: http://www.lifescied.org/content/12/4/711.full

On 2014 Apr 18, Allison Stelling commented:

L Charles Murtaugh: "reduce the temptation to package all results into "stories" that compromise messy scientific reality for the sake of superficially compelling narrative"

Well-put. As compelling- and useful, when used properly- as stories and narratives are, they can also gloss over important complexities that are part and parcel with the realities of lab work. Storytelling will always have a place in any human endeavor, but the degree to which it is currently emphasized in science can cause damaging hype and overselling.

I think there are elements of pre-publication peer review that should be kept. It is usually helpful to have senior, experienced scientists give feedback prior to presenting one's work to the Academy. (I'd quite prefer to be told if I am completely wrong about something in a semi-private fashion before I present it to the world!) However, post-publication peer review has great potential to put many eyes on data and produce robust applications that are planted upon firmly tested foundations.

bioRxiv may be the start of an inversion in biomedical publishing- I like the idea, but I also know there is much invested in the current distribution system for high quality biomedical science. (It'd be interesting to see a similar site geared towards clinical trial data.)

A recent Nature editorial, Credit where credit is due, suggests new authorship metrics as well. Such systems may help clear up exactly whom did what in the increasingly team-orientated work of life science. Biology needs teamwork, yes- but it is also important to acknowledge (and reward) all the individual contributions.

On 2014 Apr 18, L Charles Murtaugh commented:

I found Dr. Bishop's comments interesting and provocative. In particular, I quite like the idea that granting agencies should "require grantholders to write up the findings from a funded project before they are eligible to apply for further funding." This could be a great use for preprint depositories like bioRxiv. The wider use of such depositories, as a means for disseminating data from funded projects, could also reduce the temptation to package all results into "stories" that compromise messy scientific reality for the sake of superficially compelling narrative. I don't know that the entire journal system needs to be jettisoned -- I sometimes joke that the future of scientific publishing will be to dump a stack of TIFF files onto a server and issue a tweet -- but some new approach is needed to ensure access to data from publicly funded projects and, in turn, to ensure some level of reward for those who generate that data. Making data release a mandatory part of grant applications would serve these ends.

On 2014 Apr 17, Allison Stelling commented:

The other issue is that the entire United States biomedical endeavor is severely underfunded, by about an order of magnitude. Putting a man on the moon was cheap, easy, and fast compared to "curing" cancer. If we are truly at war with death, we should fund it like one.

However, simply throwing money at the problem will solve little. Self reinforcing negative feedback loops of money, power, and prestige are endemic in many American systems. They result in the inefficient allocation of resources, and consolidate that which should be fairly evenly distributed. We need a fully transparent accounting of where the money is going before more resources are pumped into the system.

We need to get universities out of professional research, and allow PIs to train their students instead of desperately writing grants which, more and more, will not get funding. We need to set up institutes to soak up the excess of biomedical "trainees" and provide them with stable work. We need more lab technicians and staff scientists to perform replications and verify discoveries.

We must parallel process the quest for cures- after all, science must happen anywhere, in any language; otherwise it is not science. It will not be one single person, department, scientific field, institute, city, State, or nation that finds such "cures". It will take all of us working together, and societies that are educated and understand why this is so very necessary.

On 2014 Apr 17, Dorothy V M Bishop commented:

Thanks to Alberts et al for opening up this discussion. While I agree with many of their points, I was rather disappointed in their proposed solutions. Their recommendations fall into three categories:

a) Improving predictability of scientific budgets

b) Changing the ways in which early-career scientists are funded, and in particular removing financial incentives for institutions to treat them as scientific serfs

c) Increase the quantity and quality of reviewing of grants

I felt that (a) would be unworkable in a world subject to unpredictable political and economic forces; (b) seemed worth serious consideration, but (c) seemed unlikely to achieve much and ran the danger of making worse the problem that scientists have in reducing the time to think and do productive work^1.

I was disappointed that the authors said very little about how we might tackle the malaise that affects the top echelons of science in many institutions, which they describe clearly in their first section: "pressure to rush into print, cut corners, exaggerate findings, overstate significance". They recognise the 'reproducibility crisis'² but it's not clear that their recommendations do anything to tackle it.

As I noted in a blogpost last year^3: "I don’t believe anyone goes into science because they want to become rich and famous: we go into it because we are excited by ideas and want to discover new things. But just as bankers seem to get into a spiral of greed whereby they want higher and higher bonuses, it’s easy to get swept up in the need to prove yourself by getting more and more grants, and to lose sight of the whole purpose of the exercise – which should be to do good, thoughtful science. We won’t get the right people staying in the field if we value people solely in terms of research income, rather than in terms of whether they use that income efficiently and effectively."

A depressing example of the consequences is here: a postdoc describing leaving the field because of pressure to distort findings^4.

I was pleased to see Alberts et al suggesting that funders should take into account the amount of funding already awarded when considering a proposal. That's a step in the right direction. But I would go further: require grantholders to write up the findings from a funded project before they are eligible to apply for further funding. Require pre-registration of research protocols, to prevent cherry-picking of results^5. Alberts et al want science to be more slow and thoughtful: I think to achieve that aim we need to change the incentives for those at the top.

References

¹ http://deevybee.blogspot.co.uk/2013/09/evaluate-evaluate-evaluate.html

² http://www.nature.com/news/independent-labs-to-verify-high-profile-papers-1.11176

³ http://deevybee.blogspot.co.uk/2013/05/the-academic-backlog.html

⁴ http://anothersb.blogspot.com/2014/04/dear-academia-i-loved-you-but-im.html

⁵ http://deevybee.blogspot.co.uk/2014/01/why-does-so-much-research-go-unpublished.html

On 2015 Feb 27, Geriatric Medicine Journal Club commented:

This study of the Confusion Assessment Method - Severity (CAM-S) was critically appraised at the first Geriatric Medicine Journal Club (follow #GeriMedJC on Twitter) in August 2014. A full transcript of the discussion can be found at http://gerimedjc.blogspot.com/2014/08/first-gerimedjc.html?spref=tw Highlights included the concern that the first cohort in CAM-S study excluded patients with dementia.

On 2014 Nov 19, Francisco Felix commented:

This report is highly provocative because it poses the question of administration density and dosing for temozolomide. Data from phase I-II trials settles the issue for two basic administration schemes. In the first one, temozolomide is given concomitant with radiotherapy at a dose ranging from 75-90 mg/m2, 5 days a week, for 6 consecutive weeks, with a cumulative total dose of 2250-2700 mg/m2. This protocol is very well tolerated with virtually no grade III-IV toxicities. The second one is a 5-day administration course with a total cumulative dose of 750-1000 mg/m2 per course and 28-day intervals. It is also very well tolerated. The dosing "scheme" inadvertently used with the reported patient can be viewed as a dose-dense version of the first protocol, with a nearly equal cumulative dose (2560 mg/m2) in about half the time span (3 weeks versus the normal 6-week interval). As such, it is probably not really correct to classify it as a >3 times normal dose, but a "regular" dose administered in a dose-dense way. Of course, this is only a way of wording and does not change the facts in no manner. The fact is it should be worthwhile to plan dose-dense phase I trials of temozolomide for pediatric patients, to test the hypothesis of this report: higher peak doses of temozolomide could overcome intrinsic tumor resistance and be more effective?

On 2014 Apr 29, Michael Kurth commented:

This review does not consider the recent findings of oocyst morphology in rodent coccidia species (Wiedmer et al. Protist. 2011 Oct;162(4):668-78.)As shown by Wiedmer et al. the micropyle and the cap are independent structure.

On 2014 May 29, David Keller commented:

Replace the USPSTF with several committees composed of experts in the disease being considered

In medicine, as in other sciences, open questions regarding Nature are settled by experimentation. If the data from an experiment yield unclear results, the outcome of the experiment should not be declared by a committee. The experiment should be refined and repeated until the data clearly indicate the answer to the question being examined.

If we have clear, unambiguous results from well-designed experiments, we do not need a committee like the USPSTF to interpret those results and declare what they mean. Conversely, if the data is so ambiguous, arguable or suspicious that a committee is required to interpret it, then that data is inadequate to base important recommendations on.

Equipoise is the state of not being certain which of two opposite courses of action is correct. Take multivitamins or not? Screen for carotid stenosis or not? Screen for prostate cancer using PSA or not? These are all very important questions with life-altering consequences for many people if we get it wrong. Equipoise exists as long as the data are so unclear that the correct answer is not obvious, and certainly as long as a committee is required to interpret the results.

The USPSTF members are part-time volunteers who are mainly occupied by other important jobs, such as running large healthcare organizations, academic departments and research enterprises. How can a pediatrician or a gynecologist on the USPSTF, for example, be expected to master, in a few hours per week, the art and science of an unfamiliar specialty such as urology or vascular surgery, which they do not practice and to which others devote their lives? They cannot, nobody is that smart or that efficient. This is why the pronouncements of the USPSTF often meet with disbelief and non-compliance among practicing physicians. When our accumulated experience informs us that certain screening tests or treatments are helpful to patients, we require convincing data to change our practices. And, given data which is convincing, alert clinicians do not need a committee to interpret it for us. The consensus of editorials and reviews in medical journals is a reliable source of guidance when it is required.

In the years following the widespread introduction of PSA screening, there was a drop of over 35% in deaths due to prostate cancer. While this is merely observational data, from which no conclusions can be drawn regarding cause-and-effect, it is still an impressive fact, which must be explained if we are asked to stop screening with PSA. One of the main clinical trials which the USPSTF relied on to arrive at their "D" recommendation for PSA screening was PLCO (for "Prostate, Lung, Colorectal and Ovarian" cancer). PLCO was hindered by the fact that 52% of the men in the control arm, who were not supposed to get PSA screening, had PSA testing done off-protocol. Yet the rigorously-applied intention-to-treat analysis demanded that these men be counted as if they had not been screened with PSA tests. With the majority of the "control" group thus contaminated, no wonder PLCO did not discern a benefit to screening versus not screening PSA (1).

In addition to giving too much credence to the flawed PLCO results, the USPSTF did not place enough emphasis on the Goteburg study, which showed robust benefits to PSA screening (1), since it was conducted prior to widespread access to off-protocol PSA testing; it may be the last trial which can ever be conducted under such pristine conditions.

There is a great deal we must do to improve how we use the PSA test, but it remains the best hope we have for maintaining the dramatic improvements in prostate cancer mortality we have seen since its widespread introduction.

Reference

1: Allan GM, Chetner MP, Donnelly BJ, Hagen NA, Ross D, Ruether JD, Venner P.Furthering the prostate cancer screening debate (prostate cancer specificmortality and associated risks). Can Urol Assoc J. 2011 Dec;5(6):416-21. doi:10.5489/cuaj.11063. PubMed PMID: 22154638; PubMed Central PMCID: PMC3235209.

On 2014 May 06, Preben Berthelsen commented:

Correction. On page 506 I wrote ”Almost 150 years ago, Francis Darwin opined: In science, credit goes to the man who convinces the world, not to the man to whom the idea first occurs.” The quotation is correct but it is incorrectly dated. Francis Darwin (1848-1925) - seventh child of Charles Darwin – wrote his words of wisdom 100 years ago, in Eugenics Review April 1914. P.G.Berthelsen, MD. Charlottenlund Denmark

On 2014 Apr 18, Christopher Southan commented:

For molecular details see: http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=summary&ligandId=198

On 2014 May 30, Amanda Capes-Davis commented:

The authors use a panel of cell lines for this work. Please be aware that KB is not epidermoid carcinoma; the KB cell line is known to be cross-contaminated with HeLa, which also appears in their panel. It is also important to test lab stocks to be sure they are not cross-contaminated, using an accepted method such as short tandem repeat (STR) profiling. For a list of known cross-contaminated cell lines, see http://iclac.org/databases/cross-contaminations/.

On 2014 May 20, Guri Giaever commented:

Erratum: In the report "Mapping the Cellular Response to Small Molecules Using Chemogenomic Fitness Signatures" by A. Y. Lee et al. (11 April 2014, p. 208), the chemical substructures, or fragments, in Fig. 2 were represented without R groups, leading some to misinterpret them as full chemical structures. To improve clarity, we revised Fig. 2 by (i) illustrating the substitution sites of fragments; (ii) labeling fragments numerically for reference to supplementary materials containing details about their derivation; and (iii) representing the dominant tautomers of signature compounds. We also discovered an error in our fragment generation software that, when corrected, resulted in slightly fewer enriched fragments being identified. In the revised Fig. 2, we removed redundant substructures and, where applicable, illustrated larger substructures containing the enriched fragment common among signature compounds. We include a table indexing the numbered fragments in Fig. 2 to the signature small molecules (table S8) and a supplemental figure (fig. S25) highlighting the enriched fragments within those molecules. In the first sentence of the penultimate paragraph, n = 20, not 28. We have also corrected a graphical misprint in the structure presented in Fig. 3 where the N-N bond was rotated in error. None of these changes affect the results or conclusions of this study. The HTML and PDF versions online have been updated to reflect the revised Figs. 2 and 3 and associated figure legend and text. The supplementary materials have been revised to add the new table and figure.

On 2014 Apr 14, Christopher Southan commented:

This paper is the subject of two technical blogposts already http://pipeline.corante.com/archives/2014/04/11/biology_maybe_right_chemistry_ridiculously_wrong.php and http://pipeline.corante.com/archives/2014/04/14/more_on_the_science_chemogenomic_signatures_paper.php

On 2014 May 22, Swapnil Hiremath commented:

This article was discussed on May 13th 2014 on the open online nephrology journal club, #NephJC, on twitter. The highlight of the chat was the active participation of Vlado Perkovic, one of the authors, who made many insightful comments.

An introductory comment is available here. A storify'd version of the tweetchat is also available at the same link.

On May 20th, there was a Google Hangout, between the NephJC editors and Dr Perkovic, which can be viewed on Youtube.

The highlights of the tweetchat were: 1. The fact that novel effective therapies are urgently needed for progressive diabetic nephropathy 2. The ASCEND trial with Avosentan reported a higher incidence of adverse events with the drug - Previous research suggests that a low dose of 0.25 mg of Atrasentan is not effective; this study suggests that 1.25 mg may be too high, and 0.75 mg may be the optimum dose 3. Patients in this trial were carefully selected to minimize the risk of adverse events (heart failure) seen with previous studies of endothelin antagonists 4. This phase 2 trial is being followed by SONAR, a 4000 patient trial with hard endpoints

Interested individuals can track and join in the conversation by following @NephJC or #NephJC, or visit the webpage at www.NephJC.com.

On 2014 Apr 17, Farrel Buchinsky commented:

Fascinating work and interesting use of large administrative database with checking against medical record. There was almost double the incidence and prevalence in the Medicaid group. So the obvious association is between lower socioeconomic status and higher RRP burden.

Can the database and analysis confirm or refute (or apply probability to) various hypotheses? For instance:

1) In 2006 many people had no insurance yet many children were eligible for state-provided insurance and could get it. Could dysphonia and dyspnea drive uninsured people into Children's Health Insurance Program (CHIP). The hypothesis may or may not be true, but even if it is true it may be way too small a number to account for the difference. It would be interesting to characterize date of enrollment as a function of date of incidence. Also remember that symptoms often precede diagnosis by a long time (about a year).

2) Does low SES ("Medicaid") cause RRP or does RRP cause low SES ("Medicaid") or does another factor "Y" cause both low SES("Medicaid") and RRP? Does data structure permit one to see if an individual moved from commercial to Medicaid as a function of disease incidence or prevalence.

3) Does the data structure permit one to explore association between frequency of interventions (as merely one metric, albeit flawed, of aggressiveness) and type of insurance?

4) In 2006, what number of the 20 million Americans less than 5 years old had no insurance and what effect would/could that number have on the estimates.

5) In my state at least, a child can qualify for Medicaid based on disease and independent of socioeconomic status. How widespread is it and can that be modeled into the data?

On 2014 Apr 25, Attila Csordas commented:

proteomics data available via PRIDE/ProteomeXchange http://www.ebi.ac.uk/pride/archive/projects/PXD000928

On 2014 Apr 29, Nikolai Slavov commented:

This deletion collection is a great resource and will enable many cool experiments.

On 2014 Apr 26, Nikolai Slavov commented:

None

On 2014 Sep 30, Ryan Radecki commented:

Post-publication commentary:

"Sedation May Not Always Be the Answer in Shoulder Reduction"

What happens when you combine Ultrasound guided nerve blocks and shoulder reduction? In the hands of experienced operators, not surprisingly, great things!

This is a randomized control trial of 41 patients out of Turkey that compared shoulder reduction utilizing procedural sedation versus an ultrasound guided suprascapular nerve block. Using the modified Kocher method for reduction, the authors found that the nerve block leads to a statistically significant decrease in pain quantified by a Visual Analog Score....

http://www.emlitofnote.com/2014/09/sedation-may-not-always-be-answer-in.html

On 2014 Nov 24, Guillaume Filion commented:

This article is one of the "CISCOM meta-analyses", which are very similar papers written by different authors. For more information about the CISCOM meta-analyses, check the blog post "A flurry of copycast on PubMed" at the following link http://blog.thegrandlocus.com/2014/10/a-flurry-of-copycats-on-pubmed

On 2014 Nov 24, Guillaume Filion commented:

This article is one of the "CISCOM meta-analyses", which are very similar papers written by different authors. For more information about the CISCOM meta-analyses, check the blog post "A flurry of copycast on PubMed" at the following link http://blog.thegrandlocus.com/2014/10/a-flurry-of-copycats-on-pubmed

On 2014 Oct 31, Francisco Felix commented:

The many technical flaws in this article should be obvious to the educated reader, but I can summarize the most prominent ones for the sake of helping the eventual reader of scientific papers. 1. Diagnostic criteria: even though there is no clear cut criteria listed for DIPG, there is a common set of characteristics for defining it. As the acronym implies, it should be DIFFUSE, meaning no evident boundaries between the lesion and surrounding brain tissue. Also, it has to be INTRINSIC, meaning it should be completely embedded in pons, with no main exophytic or extra-axial portion. Other commonly recognized features include little or no contrast enhancement of the lesion and location on the ventral aspect of pons. For my astonishment, figure 2 depicts a mesencephalic focal tumor with cystic areas, typical of a low grade glioma with good prognosis, whereas figure 3 shows an upper pons, lower mesencephalon focal, highly enhancing lesion. 2. Accrual time: why it was so long? What happened to the patients diagnosed between 1994 and 2003? This is not a trivial question. We know that DIPG comprises 15-20% of all pediatric brain tumors, so there should be a regular registration of new patients in the trial. Around 3-5% of DIPG patients show longer survival, and duration of symptoms before diagnosis and patient age are strong factors influencing survival. This patient series seems to be enriched in older patients and longer pre-diagnostic symptom duration, both factors associated with better survival. This strongly indicates a bias, and one could imagine if there was some intentional selection of patients. 3. Evaluation: once there is irregular contrast enhancement by DIPG lesions, it is simply wrong to evaluate response by measuring it. Period. Hence, no result pertaining response evaluation should be trusted in this paper. 4. Prior treatment: patients with more than one previous chemotherapy treatment should raise suspicion, because tipically DIPG patients do not survive beyond the first progression. So, a second and even a third progression seems highly unlikely. 5. Survival data: there is no median survival time reported, and the graph difficults its visual inspection. However, it probably lies before 6 months, once survival was less than 30% at one year. The lack of confidence intervals make it hard to define if this survival time reflects reality. The best estimate on literature (upper bound) is around 5 months in patients that have done radiotherapy after progression. So, where is the point? 6. Title: there is no such thing as a 'recurrent DIPG', once there are no complete responses to treatment for this disease. It should refer to 'progressive DIPG'. However, this is such a small detail when compared to the many flaws of this article that it is almost worthless to mention.

On 2015 Feb 05, Serge Evrard commented:

We have followed with interest the publication of interim results from the New EPOC trial Primrose J, 2014 and the controversies emerging around its conclusions (e.g. Nordlinger B, 2015 Primrose JN, 2014 and Hasegawa K, 2014). The unexpected result indicating shorter PFS with cetuximab, despite a higher rate of complete or partial response (70% versus 62% in the control arm) is so peculiar that a clear explanation needs to be found. The absence of residual tumor in 15% of the retrieved specimens in both arms also raises questions.

Based on findings regarding the efficacy of Cetuximab in the palliative setting, the add-on value of Cetuximab as a peri-operative adjunct to surgical treatment of colorectal liver metastases (CRLM) could be expected to be low when translated into PFS. In this context, it is clear that a small imbalance in the severity of disease across groups or in the modalities of the surgery may cancel or even inverse such a small expected improvement. A historical example of an adjuvant randomized trial that was biased by the surgery was the McDonald trial in gastric cancer where postoperative chemoradiotherapy was established as an adjuvant treatment to surgery when actually it was just necessary to make up for inadequate surgical choices. There are some possible concerns with the surgery in the New EPOC trial regarding the number of R1 resections and the use of ablation. R1 hepatectomy or use of ablation could result either from suboptimal practice in liver surgery or from lesions that are more difficult to treat. Especially intra-operative use of ablation is often used when resection cannot be done easily. Therefore, patients with more R1 margin resections and more ablation procedures might have suffered more advanced disease, which was the case for the cetuximab group.

For these reasons, we would like to call for an external audit of the patient-level data, following the increasingly-accepted principles of data transparency promoted by journals such as Plos One. Launched on an online platform initially by GlaxoSmithKline, public access to patient-level data from clinical trials is now a standard offered by many industry sponsors. As an academic trial funded by Cancer research UK, the new EPOC trial has no obligation to make patient-level data available for external audit. However, making this data available would allow validation, reanalysis and reinterpretation of these important results that potentially have a direct impact on patient care. Well-designed phase III trials are sufficiently rare in surgical oncology; the efforts of the study design committee should be lauded for their rigorous planning and carrying out of this large trial. It would be a pity for both the clinicians involved in this trial and the patients who participated, for the results to be discarded due to unsolved controversies during analysis and reporting.

Serge Evrard, Institut Bergonié, Bordeaux

René Adam, APHP Hôpital Paul Brousse, Villejuif

On 2014 Oct 11, GianCarlo Panzica commented:

Authors: M. Bonomi, M. Cappa, A. Cariboni, E. Di Schiavi, A. Fabbri, A. Ferlin, C. Foresta, L. Ghizzoni, E. Jannini, C. Krausz, M. Maggi, R. Maggi, M. Maghnie, A. Mancini, G. Merlo, G. Panzica, G. Radetti, G. Russo, M. Simoni, A. A. Sinisi, L. Persani

On 2014 Jun 06, Amanda Capes-Davis commented:

The authors use five cancer cell lines in their analysis. Please be aware that one of these cell lines, KB, is known to be cross-contaminated with HeLa and is not from nasopharyngeal epidermoid carcinoma. Cross-contamination is a common problem in cell culture; cell lines should be tested for authenticity using a technique such as short tandem repeat (STR) profiling. For a list of known cross-contaminated cell lines, see http://iclac.org/databases/cross-contaminations/.

On 2017 May 30, Rashmi Das commented:

We thank Harri for his PERSONAL (NON PEER REVIEWED) OPINION which is available at above HANDLE ( http://hdl.handle.net/10138/153180) THAT CONTAINS DIRECT COPY AND PASTE OF THREE FIGURES/IMAGES FROM OUR PREVIOUS PUBLICATIONS (JAMA 2014 and Cochrane 2013). We are happy to reply to above comments made by Harri. First regarding the Cochrane review which was withdrawn in 2015, the detailed report is already available at following link (http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001364.pub5/abstract). This report is the collaborative observation and conclusion of the Cochrane editors (UNLIKE THE HANDLE WHICH CONTAINS MORE OF PERSONAL OPINION WHICH HAS ALREADY BEEN EXAMINED BY THE COCHRANE EDITORS BEFORE REACHING THE CONCLUSION). The same HANDLE WAS SENT TO JAMA EDITORS REGARDING THE JAMA CLINICAL SYNOPSIS (PUBLISHED IN 2014) AND HARRI REQUESTED THE EDITORS TO CARRY OUT THE INVESTIGATION AND VERIFY. THE EDITORS ASKED US FOR REPLY WHICH WE CLARIFIED IN A POINT TO POINT MANNER (BOTH THE COMMENT BY HARRI AND OUR REPLY WAS PUBLISHED, SEE BELOW). HAD THE COMMENT/REPORT BY HARRI WAS ENTIRELY CORRECT, THE JAMA EDITORS COULD HAVE STRAIGHTWAY RETRACTED/WITHDRAWN THE SYNOPSIS WITHOUT GOING FOR PUBLICATION OF THE COMMENT/REPLY (Both are available at following: https://www.ncbi.nlm.nih.gov/pubmed/26284729; https://www.ncbi.nlm.nih.gov/pubmed/26284728). IT HAS TO BE MADE CLEAR THAT THE JAMA SYNOPSIS (DAS 2014) WAS WITHDRAWN AS THE SOURCE DOCUMENT ON WHICH IT WAS BASED (COCHRANE 2013 REVIEW) WAS WITHDRAWN (NOT BASED ON THE REPORT IN THE HANDLE WHICH IS A PERSONAL NON PEER REVIEWED OPINION). The irony is that though HARRI'S COMMENT got published as LETTER TO EDITOR in JAMA after OUR REPLY, still the NON PEER REVIEWED HANDLE THAT CONTAINS DIRECT COPY OF THREE FIGURES/IMAGES FROM OUR PUBLICATION IS GETTING PROPAGATED.

On 2015 Jan 04, Harri Hemila commented:

JAMA Synopsis by Das RR, 2014 is misleading about the effects of zinc on the common cold

Note added in March 2015: After I wrote the comments below, I used time to figure out explanations for the inconsistencies described below. A detailed description of serious problems with the calculations is available as a separate document at: handle.

In 2011, I wrote Feedback about the problems of the Cochrane review (2011) on zinc for the common cold by Singh M, 2011. My Feedback is available at handle, with a summary in Pubmed Commons. Some errors were corrected in the 2013 update by Singh M, 2013, but many remain.

In JAMA, Das RR, 2014 published a Synopsis of the updated Cochrane review (2013). Here I describe the main problems of the JAMA Synopsis.

1) The figures in Table are inconsistent

In the first row of the Table summarizing the zinc lozenge trials, Das RR, 2014 report that the mean duration of cold symptoms was 6.75 (SD 2.36) days in the zinc group and 7.5 (SD 4.03) days in the placebo group, and from these figures Das RR, 2014 calculate the difference as -1.04 (95%CI -2.02, -0.05) days. However, the correct difference between 6.75 and 7.5 is -0.75 instead of -1.04. In addition, the means and SDs give (95%CI -1.10, -0.40) which is much narrower than the 95%CI reported in the Table.

The same problem is seen in the second row of the Table for zinc syrup (2 studies with children). The duration of colds was 5.1 (SD 0.4) days in the zinc group, and 5.9 (SD 0.6) days in the placebo group, the Table giving the difference as -0.63 (95%CI -0.84, -0.43). However, the difference between 5.1 and 5.9 is -0.8 and not -0.63. Furthermore, the means and SDs give (95%CI -0.91, -0.69) which is inconsistent with the Table. Table is also inconsistent with Singh M, 2013, which gives -0.65 (95%CI -0.92, -0.39).

Thus, either the mean durations and their SDs are incorrect, or the estimates and their 95%CIs are incorrect. In any case the figures in the Table are inconsistent.

2) When there is strong heterogeneity, the main focus should be on trying to understand the sources of that heterogeneity, see Thompson SG, 1994

In the Table, Das RR, 2014 report that there is a high level heterogeneity in the effect of zinc lozenges on the duration of colds, with I-square=89%. Previously, Hemilä H, 2011 showed that the heterogeneity over all the zinc lozenge trials can be explained by the dosage of zinc and the zinc salt used in the lozenges. That approach was copied without citation into Fig. 4 in the Cochrane review (2013) by Singh M, 2013, which shows that 5 studies used low doses of zinc, <75 mg/d, and uniformly found no benefit of zinc, whereas 7 studies used high doses of zinc, >75 mg/d, and found a 2.0 day (95%CI 0.8, 3.1; P=0.0006) reduction in the duration of colds. Thus, the dosage of zinc is a source of heterogeneity. However, this plausible explanation for heterogeneity was not made clear to the readers of the JAMA Synopsis.

Furthermore, the third row of the Table shows the comparison “High dose vs low dose zinc lozenges.” No such comparison is published in the Cochrane review (2013). It is not evident where the data for the third row comes from.

Das RR, 2014 state that “Because of… high heterogeneity among the lozenge trials, results should be viewed with caution”, but no justification is given for that statement. When a source of heterogeneity has been identified, heterogeneity per se does not lead to any caution. Low doses of zinc are uniformly ineffective in treating the common cold, but that is no argument against the benefit of high dose zinc lozenges, which seem to reduce the duration of colds by 2 days, see above.

3) There is no basis to speculate that publication bias might explain the reported benefits

Das RR, 2014 claim that ”Because of a significant potential for publication bias … results should be viewed with caution”, but no justification is given for the concern about publication bias in the JAMA synopsis, nor in the Cochrane review (2013).

If we wish to use publication bias as an explanation for the pattern of the published findings, there should be strong correlation between the zinc dosage and the decision to publish the results. When low dose studies uniformly show no evidence of effect (still they were published), and high dose zinc lozenge studies show strong evidence of benefit, a large number of high dose negative studies should remain unpublished, to explain such a pattern. Thus, complex speculation would be needed to explain the pattern of results by publication bias, instead of explaining the pattern as the result of dose dependency.

4) Das RR, 2014 show the effect in days but the percentage effect is more useful for common cold patients

The standard practice of analyzing binary data is to calculate relative effects, which adjusts for baseline variations. In the analysis of common cold duration, relative effects should also be calculated, since these automatically adjust for variation in baseline cold durations.

In Fig. 4 of the Cochrane review (2013), high dose zinc lozenges shorten the duration of colds by 2 days, but we do not know whether the corresponding untreated colds would last for 3 or 14 days. Thus, the practical significance of the reduction by 2 days depends on the baseline duration, but that has varied over the studies. Hemilä H, 2011 calculated that high dose zinc acetate lozenges shortened the durations of colds by 43% (95%CI 35%, 48%) and lozenges made of other salts by 20% (95%CI 12%, 28%). Percentage estimates seem more useful for cold patients since they are not associated with a specific but undefined duration of untreated cold.

5) Das RR, 2014 conclude that “Used prophylactically, oral zinc is associated with a reduced cold incidence in children.” However, the findings on children are from 2 Turkish studies. There is no justification to extrapolate such findings to all children, implying validity for children in developed countries.

6) Das RR, 2014 describe findings of an RCT carried out in Thailand with children, the reporting of which is sloppy, see Pubmed Commons. Even if the findings might be valid for Thai children, they cannot be directly extrapolated to developed countries.

7) Das RR, 2014 claim that “Zinc lozenges were associated with a higher incidence of adverse events compared with placebo.” This conclusion is based on the pooling of studies that used different types of zinc lozenges. However, the adverse effects of lozenges depend on their specific compositions and pooling adverse effects of all zinc lozenge trials is unsound, see comment 9 in Pubmed Commons.

8) Das RR, 2014 conclude their JAMA Synopsis by stating that “further information on the association of zinc dose with toxicity is needed”

For certain patients, zinc has been administered at high doses, 150 mg/d, for therapeutic purposes for months and there are case reports of people taking up to 2000 mg/d of zinc for years. Many of these reports found that long-term high dose zinc decreased copper levels and led to haematological changes, but the changes were reversible with the cessation of zinc intake. See reports of high zinc doses eg by Pories WJ, 1967, Greaves MW, 1970, Simkin PA, 1976, Prasad AS, 1978, Samman S, 1987, Hoffman HN 2nd, 1988, Simon SR, 1988, Forman WB, 1990, Fiske DN, 1994, Irving JA, 2003, Bamford JT, 2012.

Thus, given that months of 150 mg/d zinc regime does not cause permanent harms, it seems evident that treating the common cold for 1 to 2 weeks with 80-90 mg/d of zinc in the form of zinc acetate lozenges does not cause unanticipated harm. Common cold patients should not be scared about the possible toxicity of short-term zinc lozenge treatment.

On 2014 May 01, Giovanni M. Dall’Olio commented:

Interesting article that explores the role of pseudogene formation by retrotranscription of mRNAs in somatic cells in cancer.

After reading the article, my impression is that pseudogene formation is not a major process driving cancer. In fact, the percentage of pseudogenes found in the cancer samples analyzed is relatively low, and only few of these cases seem to be relevant to the cancer process. However, it is very good to have an estimate of how much somatic retrotransposition is important in cancer, and to have a few examples of newly formed pseudogenes causing damage to the expression of cancer genes.

One detail that didn't convince me of the article is the result presented in Figure 3. I don't think there are enough points for the Wilcoxon test, except maybe only for the lung samples. Maybe a permutation test would be more robust, although the real problem is that there are too few data points.

A colleague of mine also noted, from Figure 1, that most of the pseudogenes observed seem to be patient-specific, rather than cancer-type specific. For example patient PD7354 (if we interpret the sample naming scheme right) seems to host half of pseudogene events observed. Can it be that this individual is somehow more prone to this process, e.g. that retrontransposon activity is higher in this individual?

It would also be useful to have an estimate of the overall mutation rate in somatic cells in the samples analyzed, to know if this correlates with pseudogene formation.

Congratulations again to the author for the work presented.

On 2014 Apr 09, David Keller commented:

Are tadalafil and vardenafil also associated with increased risk of melanoma?

Sildenafil (Viagra) was associated with increased risk of melanoma in this study, and a plausible biological mechanism was proposed to explain this association. Two other closely-related phosphodiesterase inhibitors are widely used: tadalafil (Cialis) and vardenafil (Levitra); are these drugs also associated with increased risk of melanoma? One would expect this association to be a class effect.

The results of this study will be of particular concern to men who have used sildenafil and may be at elevated risk of melanoma due to history of extensive sun exposure, basal or squamous cell skin cancers, Parkinson disease (which causes autonomic erectile dysfunction and is associated with elevated risk of melanoma) or family history of melanoma.

A recent editorial advocates adjuvant therapy with vitamin D and melatonin for every stage of melanoma, and as secondary prophylaxis versus melanoma recurrence (1). Given the low risk of harm from these supplements, might it be reasonable for persons at high risk for melanoma to consider taking them as primary prophylaxis?

Reference

1: Slominski AT, Carlson JA. Melanoma resistance: a bright future for academicians and a challenge for patient advocates. Mayo Clin Proc. 2014 Apr;89(4):429-33. doi: 10.1016/j.mayocp.2014.02.009. PubMed PMID: 24684870.

If you find this comment unhelpful, please explain why, to facilitate discussion

On 2014 May 02, Francisco Xavier Castellanos commented:

This appears to be a well-intentioned open trial with unblinded reports provided by the parents as the evidence of improvement. There is no way in which these observations can be interpreted as a "demonstration" of a "beneficial effect." Was this "clinical trial" registered on clinicaltrials.gov?

On 2014 Nov 24, Guillaume Filion commented:

This article is one of the "CISCOM meta-analyses", which are very similar papers written by different authors. For more information about the CISCOM meta-analyses, check the blog post "A flurry of copycast on PubMed" at the following link http://blog.thegrandlocus.com/2014/10/a-flurry-of-copycats-on-pubmed

On 2014 May 03, Stefanie Butland commented:

All interaction data from this paper are freely available at IntAct http://www.ebi.ac.uk/intact/query/24705354 and are featured as Dataset of the Month for May 2014. These include 312 binary interactions from yeast two-hybrid, anti tag coimmunoprecipitation, fluorescence microscopy and luminescence based mammalian interactome mapping (LUMIER) experiments.

We submitted our data directly to IntAct through the IMEx Consortium as part of the publication process. I encourage others to consider this route to making your data available for re-use and re-mixing as the expert biocuration service provided by IntAct was smooth, accurate, and required very little of our time. A very positive experience.

On 2015 Sep 30, Jan Egger commented:

This article is related to: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0031064

Best wishes, Jan

On 2014 May 23, Roy Wise commented:

It is interesting that the decrease in dopamine release that Willhun et al. found to correlate with escalated cocaine intake (decreased within-session inter-response times) was a decrease in the core rather than the shell of nucleus accumbens. Like Willhun et al., we have found that attenuated dopamine actions in the core (but not the shell) of accumbens results in greater cocaine intake—shorter inter-response times—during periods of self-administration (Suto, Psychopharmacol 205, 431-439). Conversely, we find that enhanced dopamine actions in the core (but not the shell) result in decreased intake—longer inter-response times (Suto J Neurosci 31, 17917-17922). We expected the opposite: that dopamine antagonists and agonists would increase or increase intravenous cocaine intake when infused (by reverse dialysis) into the ventromedial shell but not the core. Our hypothesis was based on the findings that reinforcing actions of cocaine take place in the shell and not the core (Carlezon, Psychopharmacol, 122, 194-197; Ikemoto, J Neurosci 23, 9305-9311); we assumed that goal of intravenous self-administration was to elevate dopamine levels at the site where dopamine (Ikemoto, J Neurosci 17,8580-8587) is rewarding. On the contrary, our experiments and Willhun’s, suggest that dopaminergic activation in the core serves quite a different function than that served by dopaminergic activation in the shell. Dopamine in the shell serves the functions of establishing and maintaining cocaine self-administration habits, whereas dopamine in the core serves the function of limiting cocaine intake, producing periods of cocaine satiation between successive injections. The mechanisms for establishing, maintaining, and reinstatement of cocaine self-administration have been studied extensively, but have not yet led to a proven medication for cocaine addiction. Perhaps it is time to turn attention to the endogenous mechanisms for what appears to be a state of drug satiety.

On 2014 May 08, Serge Ahmed commented:

This study provides important novel insights into the neurobiological mechanisms that drive escalation of cocaine intake in rats. It shows that escalation of i.v. cocaine self-administration is selectively associated with a loss of cue-induced phasic dopamine in the nucleus accumbens. Reversing this neurochemical deficit with l-Dopa (30 mg/kg) was sufficient to reverse escalated levels of cocaine intake, suggesting that cue-induced phasic dopamine plays a causal role in regulating cocaine intake.

This conclusion is rather unexpected because cocaine cues are generally invoked as key triggers of drug seeking but not as key regulators of drug taking. Perhaps one way to test this hypothesis would be to measure the effects of cue omission (or reduced cue intensity) on maintenance of cocaine self-administration. This intervention should prevent (or reduce) cue-induced phasic dopamine and thus induce an increase in cocaine intake, at least initially.

Finally, to better understand the action of l-Dopa on escalation of cocaine intake, it will be important to check whether and to what extent it also affects tonic dopamine levels during a session of cocaine self-administration.

On 2017 Oct 31, Morten Oksvold commented:

Please note that this article contains unreliable data, and should not be cited. The central ethical review board in Sweden found research misconduct in six articles by Macchiarini, including this one.

Please see the report from the Central ethical review board in Sweden: http://www.epn.se/media/2516/pressmeddelande-o-12-2016eng.pdf https://drive.google.com/file/d/0By2HqPi4t2RbYzZweVRieVVMajhJQUM0cmFMekwyRVJTUFVr/view

This information was provided by Leonid Schneider (forbetterscience.com).

On 2016 Sep 10, Morten Oksvold commented:

Before reading or citing this article, please read the reports regarding the Macchirini case:

http://ki.se/sites/default/files/karolinska_institutet_and_the_macchiarini_case_summary_in_english_and_swedish.pdf

http://ki.se/en/news/macchiarini

On 2016 Feb 14, Md. Shahidul Islam commented:

None

On 2015 Jun 23, Darko Lavrencic commented:

(R)evolving concept of spontaneous intracranial hypotension: from Georg(es) Schaltenbrand coming back to Georg(es) Schaltenbrand, see http://www.med-lavrencic.si/research/correspondence/

On 2014 Apr 05, GRAHAM COLDITZ commented:

Arising from an ARRA funded award to build capacity for cancer prevention and control in Guatemala, this paper summarizes in a way the power of linking to service providers who are keen to improve outcomes in their population. The value added from these training opportunities and return on investment keeps compounding. See, for example, the Global Health Scholars program in internal medicine at Barnes and Washington University School of Medicine. http://ghs.wustl.edu

On 2014 Dec 10, Kath Wright commented:

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

On 2017 Jul 30, David Keller commented:

This study can't tell whether avoiding sun exposure or the resulting low vitamin D levels were to blame

The authors state that "all-cause mortality is related to low vitamin D levels", and that "exposure to sunlight remains the main source of vitamin D". They did not have access to data concerning vitamin D levels or supplementation in their study. Therefore, they cannot control for vitamin D levels, nor prove that sun exposure confers any benefits beyond those associated with higher vitamin D levels, regardless of whether the vitamin D is obtained from sun exposure or by taking a supplement pill. We know that sun exposure leads to increased risk for malignant melanoma. It is unreasonable to risk a deadly skin cancer to obtain vitamin D, rather than take vitamin D in supplement form. This will not change until a study is performed which controls for vitamin D levels, and thereby demonstrates mortality benefit for sun exposure which is independent of sunlight's effect on raising vitamin D levels.

On 2017 Jul 31, David Keller commented:

Study subjects who exercise indoors, avoid solar radiation exposure & take vitamin D"

PubMed Commons commenters have difficulty responding to anonymous "unhelpful" votes which do not include any explanation or critique. I will have to guess that the study of spelunkers would be impractical (too few spelunkers) or biased (spelunkers are too distinctly different than non-spelunkers). So, instead of spelunking, substitute any form of moderate indoor exercise which includes social contact. For example, subjects who work out at indoor gyms and take vitamin D supplements at adequate doses could be compared with persons who exercise outdoors, to control for vitamin D levels and other confounding sources of bias associated with sun exposure of the skin. This is an important question, because the inherently limited findings of the Melanoma In Southern Sweden (MISS) study are being touted widely in the popular media by sunbathing advocates, which could lead to a future increase in malignant melanoma and even all-cause mortality, depending on the degree to which the MISS trial was confounded by unrecognized biases. The public generally are not informed that the MISS results do not prove that sunbathing promotes health or longevity, independent of vitamin D levels, or some other unrecognized and uncontrolled difference between sun-seekers and sun-avoiders.

On 2017 Jul 28, David Keller commented:

A proposed study to determine whether sun exposure promotes good health, or good health is a result of other factors associated with sun exposure, like sociable moderate exercise

Spelunking, the recreational exploration of caves, is an "outdoor" activity that promotes healthful cardiovascular exertion and social interaction, but zero sun exposure. The null hypothesis is that solar irradiation of the skin is not beneficial per se, and that the mortality benefits observed by Lindqvist and colleagues were due to factors associated with sun exposure, such as higher vitamin D levels, social interactions, and moderate exertion during hikes, volleyball games, etc. If sun exposure was, therefore, at best a "bystander" factor overall with regard to the mortality benefits observed in Lindqvist's study, then we ought to observe similar benefits in mortality among active spelunkers, despite the fact that they derive zero sun exposure from cave exploration. Is spelunking associated with the same benefits as sun exposure (or, are spelunkers equally self-preselected for good health) after correcting for vitamin D status? Spelunking mortality must also be corrected for the high rate of rabies from bat bites, and for trauma associated with spelunking, such as impalement injuries on stalactites and stalagmites, sudden drops into deep holes and other unseen hazards, and spelunkers who get lost in the caves and are never heard from again, who should be presumed dead, by intention to treat. Importantly, the serum vitamin D levels of spelunkers should be raised by oral supplementation until both groups exhibit equivalent levels. After those corrections, if spelunkers are found to be as healthy as those who sun-expose, we would have evidence supporting the null hypothesis, posed above.

On 2017 Jul 24, David Keller commented:

Swedes, and other depigmented peoples, should not engage in "daily, midday....sun exposure" of any duration

Depigmentation of northern peoples may seem like an evolutionary argument in favor of sun exposure to the skin. However, there is no safe threshold of solar radiation, especially for the fair-skinned, who are at the highest risk of melanoma. The risk of mutation accrues with each and every ionizing photon that hits the skin.

If there is benefit to sunbathing, then we should seek to identify and isolate the factors that provide such benefits, and advise the healthy how to maximize the benefits associated with sun exposure while minimizing its risks. The increased mortality from sunbathing is fully expressed over decades, not months or years. Older generations may have been too busy or too embarrassed to lay around near-naked in the sun. Today's generation suffers from no such inhibitions or lack of leisure time, and melanoma is now one of the fastest-increasing causes of cancer death.

My recommendation to patients, in "light" of the findings of Dr. Lindqvist and others, is as follows:

1) Avoid sun exposure to the skin. Never sunbathe. The best sunblock is clothing or shade.

2) Engage in outdoor activities that promote cardiovascular exertion and social interactions, which are healthy, while fully dressed and always seeking shade.

3) Evidence suggests that indirect light exposure can prevent or treat seasonal depression. This means that visual perception of bright light may be beneficial, but avoid direct solar radiation to the retina, which again causes melanoma. Outdoor activities in the shade safely provide this benefit.

4) Strict avoidance of sun exposure can lead to sub-optimum blood levels of vitamin D, which I suggest measuring with blood tests, and treating with vitamin D supplements. I aim for a high-normal vitamin D level.

If any other benefits of sun exposure are isolated, we should strive to find safer ways to attain those benefits. The increased risk of melanoma from sunbathing cannot be mitigated. Doctors who advise sunbathing violate the Hippocratic directive of "Primum non nocere" ("First, do no harm").

On 2017 Jul 18, P G Lindqvist commented:

Are we forcing people to choose health or melanoma? Or having a balanced discussion regarding pros and cons of sun exposure? In our observational study 2014 Lindqvist PG, 2014, we showed a strong inverse relationship between sun exposure and risk of all-cause death. Dr Keller is right that from an observational study we might not show causality. Even if we adjust for age, education, marital status, income, exercise, and smoking there might still be residual bias. The authors draw the conclusion that we might titrate a proper vitamin D dose, without raising the melanoma risk. This might be right, however, we still do not know that vitamin D is “the” mediator. Over exposure of solar radiation is a risk factor for melanoma incidence. However, as we show in our 2016 publication Lindqvist PG, 2016 using the same material. Incidence of melanoma increase with increasing sun exposure, but avoiders of sun exposure have a higher death rate if caching melanoma. Therefore, in Sweden, which is a country with scarcity of UV radiation we suggest daily, midday, short time sun exposure.

On 2017 Jul 07, David Keller commented:

Forcing a choice between vitamin D deficiency and elevated melanoma risk is a fallacy of the inevitable alternative

This observational study demonstrated that sun exposure was inversely associated with all-cause mortality. No epidemiological study, such as this, can distinguish whether lack of sun exposure caused increased mortality, or whether being destined to have increased mortality for other reasons caused reduced participation in outdoor activities that confer sun exposure.

Even if reduced sun exposure does increase mortality due to relative vitamin D deficiency, as the authors theorize, nobody would be forced to risk melanoma by exposing their skin to solar radiation. Vitamin D supplements can be titrated to match the blood levels of vitamin D achieved by sun worshipers, without raising melanoma risk.

The implication that people must choose to either raise their risk of melanoma by exposing their skin to solar radiation, or suffer morbidity and mortality from relative vitamin D deficiency is an example of the logical fallacy known as "the inevitable alternative".

Exposure of the skin to solar radiation is the number one modifiable risk factor for malignant melanoma, a cancer with rapidly rising incidence in the U.S.

The American Academy of Dermatology warns, "There is no scientifically validated, safe threshold level of UV exposure from the sun or indoor tanning devices that allows for maximal vitamin D synthesis without increasing skin cancer risk." [1]

1: American Academy of Dermatology, Position Paper on Vitamin D. Accessed on 7/5/2017 at:<br> https://www.aad.org/Forms/Policies/Uploads/PS/PS-Vitamin D Postition Statement.pdf

On 2014 Apr 23, Attila Csordas commented:

2 associated datasets available via PRIDE/ProteomeXchange, PXD000900 and PXD001258: http://www.ebi.ac.uk/pride/archive/projects/PXD000900 http://www.ebi.ac.uk/pride/archive/projects/PXD001258

On 2014 Apr 23, Attila Csordas commented:

None

On 2016 Mar 02, Atanas G. Atanasov commented:

Consumer Health Digest Scientific Abstract of this article is available at: https://www.consumerhealthdigest.com/general-health/is-yogurt-beneficial-for-healthy-aging.html

On 2014 Apr 04, Kamel Hamzaoui commented:

Yes the paper is very interesting and conclusion was true

On 2014 Jul 26, Borja Ibanez commented:

Fully agree with the comment. It is surprising that the infarct-limiting effect of b-blockers in the context of reperfused STEMI was not properly evaluated. The METOCARD-CNIC is the first trial and should be taken as a pilot endeavor. It shows that metoprolol (most probably not all b-blocker are equal in this regard) reduces infarct size. This was the primary endpoint and the trial was powered just for this outcome. All other benefits are hypothesis generating. Of note, the reduction in heart failure events could be of massive socioeconomic impact if proven in dedicated trials. There is a European multidisciplinary consortium working on the design of a large trial recruiting STEMI Pts in 8 countries randomizing them to pre-PCI metoprolol or placebo. primary outcome will be death or admission due to heart failure. This is the MOVE ON! trial. If positive, clinical practive will change. Until then, these results are the most promising in the field of cardioprotection in STEMI

On 2014 Jul 24, Ryan Radecki commented:

Post-publication commentary:

"The Return of Metoprolol – for Anterior STEMI"

Beta-blockade early in the course of myocardial infarction was once fashionable – until COMMIT demonstrated an excess of early cardiogenic shock detracting from subsequent late, favorable effects. This led to beta-blockade initiation being deferred until after hemodynamic stability established....

http://www.emlitofnote.com/2014/07/the-return-of-metoprolol-for-anterior.html

On 2014 Jul 28, Amanda Capes-Davis commented:

Please be aware that HBL-100 is known to be misidentified and it is unclear if these cells are actually from breast. Some authentic stocks may exist; stocks can be authenticated using a test method such as short tandem repeat (STR) profiling. For a list of known cross-contaminated or otherwise misidentified cell lines, see http://iclac.org/databases/cross-contaminations/.

On 2014 Apr 07, Anders von Heijne commented:

This is an interesting and important discussion. However, the cited paper by Geurts et al from 2005, that compares 3D FLAIR and 3D DIR, reports on older versions of both sequences, with scan times around 15 minutes and with rather poor image quality in the published images. Modern versions using parallell imaging renders much better image quality with higher GM-WM contrast. 3D FLAIR is also much better in showing cortical lesions than comparable 2D sequences, if not quite as good as 3D DIR. The most pragmatic approach is then, in my opinion, to use modern 3D FLAIR, with reconstructed 3mm consecutive images in three orthogonal planes for monitoring MS patients, allowing for the best trade off between scan time and detection of WM and GM lesions. 3D DIR has its place in the diagnostic phase of neuroinflammation in order to optimize the process of differential diagnosis.

On 2017 Mar 10, Pavel Nesmiyanov commented:

Logically, simple sugars (e.g. glucose) become available for the lactic bacteria other bacteria, that are cariogenic, after the enzymatic action and the toothpaste with amylase activity only promotes caries.

On 2016 Dec 19, F-C Sung commented:

I am sorry that there was a typo error in the first paragraph of dicussion. The numbers in the abstract and results were correct.

On 2016 Dec 19, Cheng-Yang Hsieh commented:

In the first paragraph of Discussion, the authors mentioned that "ESRD patients undergoing HD had an adjusted HR of 3.67 for SDH and an adjusted HR of 6.54 for SDH-associated mortality, compared with the control cohort." The numbers of "3.67" and "6.54" were different from those described in the Abstract and Results (i.e., "3.81" and "6.34", respectively). Please check.

On 2017 May 18, Misha Koksharov commented:

A version (pdf) with a couple of corrected typos in the Table S1: http://istina.msu.ru/media/publications/article/adc/55d/1722336/Koksharov_Ugarova_stability-mini-review_2012.pdf

On 2014 Apr 04, Arnaud Chiolero MD PhD commented:

An interesting study trying to disentangle the relative contribution of birth weight and weight gain at differents times during the lifecourse on cardiometabolic risk factors