PubMed

I disagree with some points presented. A reply was submitted and not accepted. But published in Bulletin of Marine Science (http://dx.doi.org/10.5343/bms.2016.1018)

Succession of generations is still the general paradigm for scyphozoan life cycles

Abstract: A recent study proposed an unorthodox view of the long-known metagenetic life cycle of scyphozoan jellyfish. We argue that misinterpretations and imprecise information generated a misleading view of such life cycle patterns. In favor of our reasoning, we present the historical understanding of metagenesis, and contend that it can still be used as a shared general life cycle pattern for Scyphozoa, as well as for other medusozoans.

This paper is part of two dissertations (2016), here: http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-125925 and here: http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-123313

This paper is part of a dissertation (2016), available here: http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-125925

A Corrigendum for this article (10.1210/jc.2012-1444) was published on May 10, 2016: http://dx.doi.org/10.1210/jc.2016-1651.

We recently identified an error in the week 30 resting metabolic rate (RMR) data in the above manuscript. In Table 1, the RMR at week 30 in the full 16 subject sample was (mean ±SD) 2015 ±332 kcal/d such that there was a decrease from baseline of 664 ± 469 kcal/d (p<0.0001) with a significant metabolic adaptation of -370 ± 290 kcal/d (p<0.0001). Also in Table 1, the week 30 RMR of the 11 subjects completing measurements at 6 weeks was 1926 ± 328 kcal/d (p=0.001 vs. baseline) and the metabolic adaptation of -345 ± 239 kcal/d (p=0.0004) was no longer significantly different from week 6 (p=0.082). A corrected Figure 2 was published in the Corrigendum.

In Figure 3A, non-resting energy expenditure at week 30 was 1129 ±399 kcal/d and significantly lower than baseline (p=0.04). Physical activity at week 30 shown in Figure 3B was 4.4 ±3.3 kcal/kg/d higher than baseline (p < 0.0001) and significantly lower than week 6 (p =0.02). The previously reported correlation of metabolic adaptation with weight loss at week 30 remained significant (r=0.56, p=0.038) but the correlation with TSH change was no longer significant (r=0.16, p=0.61). The authors regret this error.

Consumer Health Digest Scientific Abstract based on this article is available at: https://www.consumerhealthdigest.com/general-health/obesity-metabolic-inflammation-and-insulin-resistance.html

Calculate the Alvarado score online or using a mobile app http://qxmd.com/calculate/calculator_269/alvarado-score-for-acute-appendicitis

Calculate the Sequential Organ Failure Assessment (SOFA) score online or using a mobile app at https://www.qxmd.com/calculate/calculator_268/sequential-organ-failure-assessment-sofa

The following conclusion drawn by the authors has no foundation in the study:

In conclusion, our study strongly suggests that electronic cigarettes are not as safe as their marketing makes them appear to the public.

There are three main concerns about how this conclusion is drawn:

Firstly, the paper makes no assessment of electronic cigarette marketing claims. I am not aware of any marketing claims for complete safety and the authors do not provide any evidence that this is a common or even exceptional claim made by those marketing e-cigarettes.

Secondly, a cell study of this nature can provide no useful information on the magnitude of the human health risks or whether such risks are even material at all. It is impossible, therefore, to say if any marketing claims are reasonable or misleading on the basis of this study.

Thirdly, the study does provide evidence - though this is buried and barely referred to - that e-cigarette vapour has a much lower impact than tobacco smoke, at least when measured using this methodology. Cells were still alive in the e-cigarette vapour medium after 8 weeks, but all were dead in the tobacco smoke extract within 24 hours. It tends to support, therefore, the more common argument that e-cigarettes are much less hazardous than smoking, but may not be 100% safe.

This has most recently been expressed by the Royal College of Physicians (London) in its major assessment of e-cigarette science, Nicotine with smoke: tobacco harm reduction

Although it is not possible to precisely quantify the long-term health risks associated with e-cigarettes, the available data suggest that they are unlikely to exceed 5% of those associated with smoked tobacco products, and may well be substantially lower than this figure. (5.5)

A more detailed and critical discussion of this paper and the related irresponsible media handling was published in May 2016 and should be read by anyone reading or citing Yu V, 2016

Holliday R, Kist R, Bauld L. Commentary, Evidence-Based Dentistry (2016) 17, 2–3. doi:10.1038/sj.ebd.6401143

Media handling

In a quote in the media release one of the authors, Dr Wang-Rodriguez, asserted that evidence so far available shows no difference in risk between cigarette smoking and e-cigarette use.

The overarching question is whether the battery-operated products are really any safer than the conventional tobacco cigarettes they are designed to replace. Wang-Rodriquez doesn't think they are. "Based on the evidence to date," she says, "I believe they are no better than smoking regular cigarettes."

This extraordinary and unqualified assertion created worldwide news headlines (for example, E-cigarettes are no safer than smoking tobacco, scientists warn - The Telegraph).

However, this assertion has no foundation whatsoever in the study. To the extent that the study shows anything about health risks, it shows this assertion to be false. Looking beyond this study, there is no science that supports such a claim anywhere and plenty that bluntly refutes it.

As a result, the interpretation of the findings in this study and the subsequent media handling have attracted severe criticism, for example:

• Clive Bates (this author) - Counterfactual

• Dr Michael Siegel - Boston University School of Public Health

• Adam Jacobs - medical statistician

Posted on behalf of the American Academy of Sleep Medicine:

These recommendations for the use of adaptive servo-ventilation for the treatment of congestive heart failure related central sleep apnea are updates to the 2012 recommendations found in the guideline "The treatment of central sleep apnea syndromes in adults: practice parameters with an evidence-based literature review and meta-analyses." These recommendations serve as an essential supplement to the 2012 practice parameter document:

Aurora RN, 2012

We apologize, but at the time of submission, the mutation was not referenced in retina international database, and in HGMD (human gene mutation database in free access).

Robert Jackler assumes a priori that attracting adolescents to vaping through flavour descriptors is a bad thing. Saul Shiffman provides a compelling defence of their study showing that teenage interest in flavours was low and this should not concern us much. But this framing may be an over-simplification.

E-cigarette appeal may be good for health

What if the rise in e-cigarette use among adolescents is displacing tobacco smoking, and that this effect accounts for the rapid fall in teenage smoking measured in both the NYTS survey: Tobacco Use Among Middle and High School Students — United States, 2011–2014 and the University of Michigan Monitoring the Future survey, Media release: Teen cigarette smoking drops to historic low in 2015?

In that case, critics must contemplate the idea that e-cigarettes have a harm reduction function among adolescents and that their attractiveness to young people who would otherwise become smokers may be overall a public health benefit. Levy DT, 2016 shows that e-cigarettes create many beneficial pathways for the evolution of nicotine use and abstinence. It is far from clear that obstructing these pathways with policies or campaigning communications is positive for public health.

Scope for adverse unintended consequences

There is already evidence that measures designed to block youth access to e-cigarettes have adverse unintended consequences on youth smoking: see Friedman AS, 2015 and Pesko MF, 2016 on the impact of e-cigarette age restriction laws on cigarette smoking. It is not a great leap of logic to hypothesise that making e-cigarettes less attractive to adolescents would attenuate the decline in smoking that is, or should be, the primary concern in tobacco policy.

The appropriate focus is on adults

The right way to address this issue is not to try to micro-manage adolescent behaviours but to ensure that adults have attractive alternatives to smoking. Restrictions imposed with the misguided purpose of 'protecting' adolescents from very low-risk alternatives to cigarettes could have the effect of harming longstanding adult smokers - the real at-risk group. Several surveys (e.g. Farsalinos KE, 2014) have shown that non-tobacco flavours matter to adults who are using e-cigarettes as an alternative to smoking and are part of the long-term transition away from tobacco use.

Conclusion

Anyone proposing a ban on certain flavours or flavour descriptors needs to assess the risk of harmful unintended consequences - that more adolescents will take up smoking instead of vaping, and that adults smokers will find vaping a less attractive alternative to smoking and never switch, remain as dual users, or relapse back to smoking.

The post released by AG Atanasov, revealed the wide interest that CoQ has arisen in health debates. He explained, in a a few words and for a public which is not professionally involved in health care, where, how and why CoQ has a critical/strategic role in our physiology and well-being. When I began to investigate CoQ antioxidant properties in health and disease in addition to the well-known role in the mitochondrial respiratory chain of this molecule, about 25 years ago, I was considered one of the pioneer in the field and several criticisms arose from reviewers (e.g., it took more than 2 years to publish DOI: 10.1016/0003-2670(91)80070-A and DOI: 10.1016/0098-2997(94)90016-7 and also DOI: 10.1024/0300-9831.69.4.243 suffered important delays). 25 years later, CoQ is widely recognized as an active compound with important features which go beyond its primitive redox role and also those antioxidant properties my group proposed at the beginning. Nowadays, we have clear proofs of its involvement in several pathologies and we directly found evidences it has, among others, key roles in aging (doi: 10.1093/gerona/glv063, doi: 10.1016/j.freeradbiomed.2011.02.004, doi: 10.1016/j.mad.2009.11.004, DOI: 10.1023/A:1023754305218), in periodontal diseases (doi: 10.1016/j.phrs.2014.10.007, doi: 10.1016/j.fct.2009.06.026, doi: 10.1016/j.numecd.2009.03.003), in fibromialgia (doi: 10.1089/ars.2013.5198, doi: 10.1089/ars.2013.5260), in Papillon-Lefevre Syndrome (DOI:10.1080/1071576031000083116) and in modulating the effects of nutrients as outlined by this very last review (doi: 10.3390/molecules21030373).

Four of the five BEST1 variants published to be novel had been published before (p.Leu294Phe, p.Phe84Val, p.Gly83Asp, p.Trp93Arg, p.Trp309Arg).

In June 2015 we published our paper “The smoking population in the USA and EU is softening not hardening” in the journal Tobacco Control. We showed that as smoking prevalence has declined over time, quit attempts increased in the USA and remained stable in Europe, US quit ratios increased (no data for EU), and consumption dropped in the USA and Europe. These results contradict the hardening hypothesis which is often used as part of the tobacco industry’s strategy to avoid meaningful regulation and protect its political agenda and markets, claiming that there is a need for harm reduction among those smokers who “cannot or will not quit.” Indeed, rather than “hardening” the remaining smoking population is “softening.”

In February 2016 we received an email from Robert West, editor of the journal Addiction, informing us that Addiction was about to publish an article by Plurphanswat and Rodu entitled “A Critique of Kulik and Glantz: Is the smoking population in the US really softening?” whose sole purpose was to critique our Tobacco Control paper, and offered to let us respond to the criticism.

The fact that Plurphanswat and Rodu sent their paper to Addiction was unusual because normal scientific procedure would have had them sending a letter to the editor of the journal that originally published the work (Tobacco Control).

As detailed below, we did respond, noting that Plurphanswat and Rodu’s paper followed the well-established pattern of tobacco industry-funded researchers trying to create controversy about research inconsistent with industry interests, the fact that Rodu had understated his financial ties to the industry, and, of course, showing how their criticism was based on statistical error that they made.

Addiction rejected our response because we would not delete the first two points and limit our response only to the statistical issue.

This blog post includes the response that Addiction rejected so that readers of Plurphanswat and Rodu’s critique do not think we did not have a response. We also include a summary of our interactions with the journal and the related email correspondence.

THE REJECTED RESPONSE

Consider the Source

“Harm reduction” is a key part of the tobacco industry’s strategy to avoid meaningful regulation and protect its political agenda and markets.[1] This agenda is premised on the existence of “hard core” smokers who “cannot or will not” quit.[2-4] Our paper, “The smoking population in the USA and EU is softening not hardening”,[5] undermined this agenda because it showed that, contrary to the hardening hypothesis, as smoking prevalence has declined over time, quit attempts increased in the USA and remained stable in Europe, US quit ratios increased (no data for EU), and consumption dropped in the USA and Europe.

There is a longstanding pattern of tobacco industry-funded experts writing letters criticizing work that threatens the industry’s position, first described in 1993 by then-JAMA Deputy Editor Drummond Rennie.[6] Rodu and various co-authors have written several such letters.[7-10] Another similarity to past efforts is industry-linked experts submitting critiques of a paper published in one journal to another,[11-15] which is also the case here, with this critique of our paper published in Tobacco Control being published in Addiction. One would have expected any criticism to have been published as a letter in Tobacco Control.

Addiction requires “full disclosure of potential conflicts of interest, including any fees, expenses, funding or other benefits received from any interested party or organisation connected with that party, whether or not connected with the letter or the article that is the subject of discussion.” As with another investigator supported by the tobacco industry,[16] the conflict of interest statement Plurphanswat and Rodu provide may not truly reflect the extent of Rodu’s involvement with the tobacco industry. For example:

• Rodu’s Endowed Chair in Tobacco Harm Reduction Research at the University of Louisville is funded by the U.S. Smokeless Tobacco Company (US Tobacco) and Swedish Match North America, Inc.[17]

• Rodu is a Senior Fellow at the Heartland Institute, which has received tobacco industry funding.[18-20]

• Rodu is a Member and Contributor to the R Street Institute, which has received tobacco industry funding.[19,21]

• Before moving to Louisville, Dr. Rodu was supported in part by an unrestricted gift from the United States Smokeless Tobacco Company to the Tobacco Research Fund of the University of Alabama at Birmingham.[8]

• Rodu was a keynote speaker at the 2013 Tobacco Plus Expo International, a tobacco industry trade fair to discuss “How has the tobacco retail business evolved; where was it fifteen years ago, where is it today and where is it going”.[22]

• Rodu has worked with RJ Reynolds executives between at least 2000 and 2009 to help promote industry positions on harm reduction, including specific products.[23-26]

The substance of Plurphanswat and Rodu’s criticism is that the statistically significant negative association between smoking prevalence and quit attempts and the positive association between prevalence and cigarettes smoked per day both become non-significant when more tobacco control variables are included in the model (state fixed effects, cigarette excise taxes, workplace smoking bans and home smoking bans). The problem with including all these variables is that it results in a seriously overspecified model, which splits any actual effects between so many variables that all the results become nonsignificant. The regression diagnostic for this multicollinearity is the Variance Inflation Factor (VIF); values of the VIF above 4 indicate serious multicollinearity. For the United States, adding all the other variables increases the VIF for the effect of changes in smoking prevalence from 1.8 in our model for quit attempts to 16.7, and from 1.8 in our model to 17.9 for cigarettes per day, respectively. Plurphanswat and Rodu’s model is a textbook case of why one has to be careful not to put too many variables in a multiple regression.

The Plurphanswat and Rodu criticism misrepresents our conclusions. We did not argue that drops in prevalence caused increased quit attempts and reduced consumption; we simply present the observation that, as prevalence falls, quit attempts increase and consumption fall or remain constant, which is the exact opposite of what the hardening hypothesis predicts.

The references and the full email correspondence with Addiction is available at http://tobacco.ucsf.edu/addiction-refuses-allow-discussion-industry-ties-criticism-our-“softening-paper”

Read about the integration of Reactome pathways into WikiPathways is this new paper: http://dx.doi.org/10.1371/journal.pcbi.1004941

The DAPT Score can be used online or via a mobile app http://qxmd.com/calculate/calculator_373/dapt-score

Did the physical activity increase in the intervention group? Did insulin sensitivity improve? Is it possible that this was the reason for the lack of effect?

FACTS BEFORE COUNTERFACTS

Counterfactual explorations can provide intriguing insights (1). But we have to be sure that the facts themselves are correct in the first place. In the context of Weldon, reference to "bad-tempered conflict with Mendel’s followers," really means conflict with William Bateson. While it is correct that the doctrinaire "Mendelian ‘genes for’ approach is increasingly seen as out of step with twenty-first-century biology" (1), for Bateson (1861-1926) the approach was also seen as out of step with twentieth-century biology.

Well aware of developmental and environmental factors, Bateson recognized that the biochemical characterization of genes should be high on the twentieth century research agenda. Thus, near the end of his life he declared that “Our knowledge of the nature of unorganized matter must first be increased. For a long time we may have to halt” in getting to grips with the underlying biological principles (2). However, he argued forcefully for looking beyond the visible characters of an organism (its conventional phenotype) to what we now regard as its genome phenotype (3). It was here that the answer to Darwin's fundamental question - the origin of species - was likely to lie.

Weldon had allied himself with Pearson whose brilliant work (later built on by Fisher), was to create modern biostatistics. But those were early days and they made elementary mistakes that Bateson was quick to point out. For example, Bateson would have bridled at the idea that “first year biologists” could serve as a reliable “control” against which to compare “second year humanities undergraduates” (1). Yes, we should “study Mendel, but let him be part of his time”(1). And as related by Meijer (4), Mendel followed the statistics of his time. Indeed, his results have withstood the test of time.

(1) Radick G (2016) Teach students the biology of their time. Nature 533:293 Radick G, 2016

(2) Cock AG, Forsdyke DR (2008) "Treasure Your Exceptions." The Science and Life of William Bateson. Springer, New York.

(3) Forsdyke, D. R. (2010) George Romanes, William Bateson, and Darwin's "Weak Point." Notes Rec R Soc Lond 64:139-154.

(4) Meijer OG (1982) The essence of Mendel’s discovery. In: Gregor Mendel and the Foundations of Genetics. Orel V (ed). The Mendelianum of the Moravian Museaum, Brno, pp. 173-200.

A grant application is not a clinical trial registration. The content of such an application is not a blueprint of the research but merely an indication of what the researchers contemplate. What counts scientifically is the pre-trial registration of the study with ClinicalTrials. To finalise the discussion on the question of the aim of the study, I have copy pasted below the Primary Outcome Measure from the ClinicalTrials registration (NCT01680744).

Primary Outcome Measures: • Renal Function [ Time Frame: 12 hours of mild hypothermia ] [ Designated as safety issue: No ] The primary outcome measures are renal function as determined by creatinine and cystatin c between declaration of neurological death and organ recovery in each of the two treatment groups. Delta creatinine and terminal creatinine are important predictors of graft quality and function, as demonstrated in the present data (HRSA study and Region 5 DMG/DGF study), and will be compared between the control and treatment group.

Ethical Problem. If the authors planned - as the thorny lifeline thrown by Dr. Greenwald (HRSA) seems to suggest - to study recipient graft function all along, the kidney recipients should have been informed that they took part in a randomized clinical trial and they should have given their consent before being enrolled in the investigation. This did not happen.

Preben G. Berthelsen, M.D. Charlottenlund, Denmark.