PubMed

It is important to emphasize that our study is about documented disclosure of information that should be provided to patients in accordance with minimum ethics standards for consent to IVF. Most of the critical points made by Hilde Bastian are openly avowed in the limitations section of the paper. We explicitly acknowledged the declining participation rate over time and the fact that fewer of the participating Canadian IVF clinics provided us with information sheets. To be clear, the documents we very specifically requested and the documents we reviewed (as stated in the article) were ‘consent documents’ comprised of both consent forms and accompanying information sheets.

As regards our content analysis, disclosure elements were deemed present if mentioned anywhere in the consent documents reviewed. Mere mention of a keyword (or keywords) for an information element was sufficient for that element to be deemed present as part of documented disclosure. We used this strategy to remove any subjectivity as regards the quality of disclosure, and to be as generous as possible (from a clinic perspective) as regards any conclusions that might be drawn. In practice, this meant that if a consent form indicated that information about a disclosure element was in an accompanying information sheet, that element would have been judged as present just on the basis of the keyword and/or a rudimentary description alone.

Thus, while Bastian is correct that information elements might have been present in the information sheets known to exist but not provided to us, reasonable efforts were made to minimize this possibility. We could do no better given that we could only work with the consent documents that the clinics provided. For the 2014 data set, all clinics were sent an initial request by email followed by a posted letter. If there was no response, those remaining were contacted at least once by telephone. In our estimation, there is nothing more we could have done to generate better and more comprehensive information without increased collaboration by Canadian IVF clinics.

We stand behind our conclusion that “the disclosure of information relevant to the interests of those undergoing IVF and those who are born as a result of IVF appears to be decreasing. Furthermore, the information that increasingly is being disclosed in consent documents appears to be directing the orientation and content of these documents away from the primary interests of the relevant women, couples, and children.” [emphasis added] This general and avowedly tentative conclusion is consistent with the limited representativeness of the data and this we openly acknowledged.

Conflicting conclusions.

In abstract: "Bleeding disturbances, the most frequent reason for method discontinuation, were significantly more common in the ENG group [16.7 (95% CI 14.4-19.3)] than in the LNG group [12.5 (95% CI 10.5-14.9)] (P 0.019)."

A P value < 0.05 with overlapping 95% Confidence Intervals sugests that a different statistical test was used.

In the paper results it is written: "The frequency of symptoms and signs reported in the course of the study by ENG- or LNG-implant users is shown in Table II together with diagnoses of PID. Apart from more reports from ENG-implant users about amenorrhoea, therewere no significant differences recorded between the two implant groups."

And in discussion: "In conclusion, this RCT showed that the ENGand LNG implants have the same contraceptive effectiveness and similar reasons for implant removal for all combined medical reasons in the 3 years after insertion, continuation rates for the two implants were similar up to the middle of the third year of use and had, during this time period, higher continuation rates than the TCu380A IUD."

Full list of Altmetric to 50 Dental Articles-2014 is available via:

http://www.nature.com/bdj/journal/v220/n11/extref/sj.bdj.2016.411-s1.pdf

Adding to the discussion on the role of monoamines in violent aggression, this new data shed light on results we published many years ago on three models of aggression in REM sleep deprived rats. Aggression can be elicited in these animals by dopaminergic agonists like apomorphine, dopamine/noradrenaline precursor L-DOPA and noradrenaline synthesis inhibition by fusaric acid. We observed the clear differences in these three models and fusaric acid induced the more violent aggression while L-DOPA the most stereotyped mild boxing type. Our discussion proposed then that noradrenergic transmission was responsible for moderating the behavior while dopamine was triggering it. We offer the full paper at: Troncone LR, & Tufik, S. - Physiology & Behavior (1991), 50, 173-178 (PMID 1946713).

The method employed in this study offers no control over the 10⁵ statistical tests performed. The results are can not be considered statistically significant or a meta-analysis.

The version of GingerALE used (2.3.2) is known to produce false positive results due to a bug; fixed at 2.3.6. The results can not be considered valid. Furthermore, there is no control for type 1 error rate when comparing HC and patient groups, which is not appropriate given the 10⁵ statistical tests performed.

Manuscript was featured as the cover page article: http://medcraveonline.com/GHOA/archive

The method employed here offers no protection against type 1 error rate. It cant be considered a meta-analysis. Uncorrected p-values provide no evidence of statistical significance when large numbers of voxel-wise tests are performed.

The version of GingerALE (2.1.1) has a bug that results in false positive results. The results in this publication are not valid. There was a fix at version 2.3.3

This study was commented on as the principle subject of two Correspondence articles in Development:

Transcriptional interpretation of Shh morphogen signaling: computational modeling validates empirically established models. Uhde CW, Ericson J. Development. 2016 May 15;143(10):1638-40. doi: 10.1242/dev.120972. No abstract available. PMID: 27190032

and

Mathematical models help explain experimental data. Response to 'Transcriptional interpretation of Shh morphogen signaling: computational modeling validates empirically established models'. Cohen M, Page KM, Perez-Carrasco R, Barnes CP, Briscoe J. Development. 2016 May 15;143(10):1640-3. doi: 10.1242/dev.138461. No abstract available. PMID: 27190033

The methods employed provide no control over the type 1 error rate. There is no evidence that the results are statistically significant.

The version of GingerALE used (2.3.4) had a bug that produced false positive results. This was fixed at version 2.3.6

The methods employed in this study are not corrected for multiple statistical tests; uncorrected p-value. This can therefore not be considered a meta-analysis as there is no evidence of statistical significance. The results can not be considered valid.

See a letter to the editor "Greater electromyographic responses do not imply greater motor unit recruitment and 'hypertrophic potential' cannot be inferred" regarding the data in this paper: http://www.ncbi.nlm.nih.gov/pubmed/26670996

This paper reports that an NR1H3 variant, rs61731956, encoding p.Arg415Gln, causes familial multiple sclerosis (MS) (Wang Z, 2016). We have some major concerns about the evidence for the effect of the R415Q variant on risk for MS, which rests on two pedigrees with imperfect segregation with disease.

The reported data allows us to provide an estimate of penetrance for the R415Q variant. This variant was found in 1 out of 2053 individuals in a multiple sclerosis case series, but is also seen (as the authors note in passing) in 21 individuals among the 60,706 present in the Exome Aggregation Consortium (ExAC) collection (11-47290147-G-A). Enrichment in cases over controls is one important criterion for establishing pathogenicity of sequence variants (MacArthur DG, 2014, Richards S, 2015).

The ancestry distribution of the case series reported in Wang Z, 2016 is not stated, but the series was collected in Canada and appears to be of predominantly European ancestry (Sadovnick AD, 1998, Traboulsee AL, 2014). The 21 individuals with this variant in ExAC are all of non-Finnish European ancestry, with 66,738 non-Finnish European chromosomes having genotype calls for this variant. Thus, the variant is not significantly enriched in cases over ExAC population controls (P = .56) - indeed, its allele frequency is lower in MS cases (0.02%) than in ExAC European population controls (0.03%).

A review of lifetime risk estimates for MS found the best estimates of lifetime risk of MS to be 0.25% for women and 0.14% for men (Alonso A, 2008, see Table 1). Using the allele frequencies observed in ExAC and in the case series, along with these estimates of lifetime risk, we can apply formulae for calculating the penetrance or lifetime risk, and confidence intervals thereof, for reportedly Mendelian variants as described in (Kirov G, 2014, Minikel EV, 2016). The upper bound of the 95% confidence interval is 1.7% for women and 0.9% for men, indicating that this variant contributes extremely weakly, if at all, to MS risk.

The functional characterization of the effects of the p.Arg415Gln variant on gene function, while potentially interesting, does not provide independent support for a role of this gene in MS risk.

We urge the community to consider rigorous statistical approaches and independent replication before making strong claims of pathogenicity. In this case, publicly available data (and indeed data that are actually noted in the paper) are sufficient to strongly suggest that this variant has little or no effect on MS risk. Independent analyses of this variant in large case-control studies of MS are needed, and we look forward to seeing the results of such analyses from the MS community in the near future.

Eric Vallabh Minikel and Daniel MacArthur, Broad Institute of MIT and Harvard

Pointers to the F1000 recommendation and molecular mapping details at https://cdsouthan.blogspot.se/2016/06/bace1-inhibitor-post-for-f1000.html

This is a helpful broad brush update on randomized controlled trials (RCTs) of peer review interventions in biomedical journals (see older review Jefferson T, 2007 and my comment on that review). However, while the authors list several limitations, including restricting to RCTs and to biomedical journals, there are other limitations that, in turn, highlight the impact of those limitations.

One of those is the outcomes addressed here. The focus is explicitly on the peer reviews themselves and the process, and not wider outcomes, such as potential benefits and harms to peer reviewers or the impact of policies such as open review on journals (e.g. level of unwillingness to review).

In particular, the issue of harms brings us back to the limitation of looking only at RCTs, and limiting to the biomedical literature and a limited scope for databases searched. The authors provide no rationale for limiting the review to biomedical publications. Given that there are so few eligible studies within the scope this review, moving past this is essential. (In a blog post on anonymity, openness, and blinding of peer review in March 2015, in addition to the 11 RCTs identified in this systematic review, I identified a further 6 comparative studies, as well as other types of studies relevant to the questions around which known concerns exist.)

Peer reviewers are not just a means to an end: biases of peer reviewers can have a major impact on the careers of others, and at a minimum, specifically addressing gender, seniority, and institutional/country/language impact is critical to further work on this topic. A more contextual approach is needed to grapple with the complex ecosystem involved here.

A final point that is less likely to have had an impact, but is worth consideration by others working on this issue. Limiting the search strategy to the single term "peer review" may have an impact on searches, as terms such as open review and post-publication review become more widely used. Terms such as manuscript and editorial review, and peer reviewers could also be considered in constructing a search strategy in this area. (To identify the studies to which I refer above, Google Scholar and a wider range of search terms was necessary.)

(Disclosure: Part of my job includes working on PubMed Commons, which does not allow anonymous commenting.)

Kari Poikolainen and I sent a letter to the Lancet about this paper. It was not published. The content is as follows

The authors report no association between level of alcohol intake and a composite health measure. They write that "In summary, our study shows that current drinking is not associated with a net health benefit." What they fail to mention is that their study also "shows" that current drinking is not associated with net health harm. The interpretation, "sufficient commonalities to support global health strategies and national initiatives to reduce harmful alcohol use" does not follow from their study, which taken on its own suggests that there is no need for such initiatives. However there are a number of methodological problems with their data and analysis. The follow-up time (median 4.3 yrs) was short and the proportion of alcohol consumers (33%) small. There is a strong implication of overfitting, and in the stratified analyses in particular a shortage of degrees of freedom. Since a large body of earlier well-conducted studies shows evidence of both benefits and harms it would be inappropriate to base conclusions on this work.

The HOSPITAL score can be used online and in mobile apps here: http://qxmd.com/calculate/calculator_353/hospital-score