Selected recent comments - more about this
- Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis.
JAMA. 2013.2 commentsMarcus Munafò also commented
John Spitzer2015 Apr 18 4:41 p.m. (6 hours ago)edited 1 of 1 people found this helpful
The article in JAMA by Flegal et al is a summary of the literature. It includes 97 articles with 2.88 million individuals and more than 270,000 deaths. The conclusions described as "misleading" by Munafò et al (below) are simply a summary of the results that arise from the data and the statistical methods. Munafò et al do not present any specific criticisms of the methods of the Flegal et al article nor do they assert that the summary of the literature is incorrect. The single study by Lawlor, described by Munafò et al as "large," based its results on 5,337 never-smoking participants, and it was one of the articles included in the review by Flegal et al. The majority of those articles do not show smoking and pre-existing illness as important causes of bias. Opinions about "detrimental" public health messages arising from scientific findings should be distinguished from scientific criticisms of those findings. In a commentary on reactions to the Flegal et al article the editors of Nature stated: "It is risky to oversimplify science for the sake of a clear public-health message." http://www.ncbi.nlm.nih.gov/pubmed/23936910
- Early asymmetry of gene transcription in embryonic human left and right cerebral cortex.
Science. 2005.1 comment
Dorothy V M Bishop2015 Apr 18 03:26 a.m. (19 hours ago) 2 of 2 people found this helpful
As a psychologist interested in the genetics of lateralization, I frequently come across this paper, which is cited as evidence for early genetic influences on brain asymmetry. As of today, 160 citations are shown in Web of Science.
When I read the paper a couple of years ago, I found some details that did not seem to support the conclusions of the authors. These are described in a blogpost: http://deevybee.blogspot.co.uk/2012/12/genes-brains-and-lateralisation-how.html
I will summarise the main issue below, but I was interested to note that, since that time, other papers have appeared, using larger datasets, which have stressed the remarkable symmetry of early gene expression, notably:
Johnson, M. B., et al (2009). Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron, 62(4), 494-509. doi: 10.1016/j.neuron.2009.03.027
and
Pletikos, M., Sousa, A. M. M., Sedmak, G., Meyer, K. A., Zhu, Y., Cheng, F., . . . Sestan, N. (2014). Temporal specification and bilaterality of human neocortical topographic gene expression. Neuron, 81(2), 321-332. doi: 10.1016/j.neuron.2013.11.018
Here is a brief account of the main issue I raised about the study. Please see the blogpost for more details.
Sun et al used a method called Serial Analysis of Gene Expression (SAGE) which compares gene expression in different tissues or – as in this case – in corresponding left and right regions of the embryonic brain. The analysis looks for specific sequences of 10 DNA base-pairs, or tags, which index particular genes. SAGE output consists of simple tables, giving the identity of each tag, its count (a measure of cellular gene expression) and an identifier and more detailed description of the corresponding gene. These tables are available for left and right sides for three brain regions (frontal, perisylvian and occipital) for 12- and 14-week old brains, and for perisylvian only for a 19-week-old brain. The perisylvian region is of particular interest because it is the brain region that will develop into the planum temporale, which has been linked with language development. One brain at each age was used to create the set of SAGE tags.
To verify asymmetrically expressed genes the authors performed chi square tests. The chi square involves testing whether the distribution of expression on left and right is significantly different from the distribution of left vs. right expression across all tags in this brain region – which is close to 50%. In the left-right perisylvian region of a 12-week-old embryonic human brain, there were 49 genes with chi square greater than 6.63 (p < .01): 21 were more highly expressed on the left and 28 more highly expressed on the right. But for each region the authors considered several thousand tags. My analysis indicated that the number of asymmetrically expressed genes appeared to be lower than you would expect by chance – entirely consistent with the conclusions of Pletikos et al.
Unless my analysis is mistaken, it would seem this paper should not be cited as evidence for asymmetric fetal gene expression, as it actually shows the opposite.
- Plant biology. Suppression of endogenous gene silencing by bidirectional cytoplasmic RNA decay in Arabidopsis.
Science. 2015.1 comment
Alexis Maizel2015 Apr 17 02:50 a.m. (yesterday)
Great article. Nicely confirms the results of Martinez et al. showing that decapping prevents the entry of endogenous mRNAs to the PTGS pathway and therefore the production of rogue siRNAs (http://nar.oxfordjournals.org/content/43/5/2902.long).
- Retraction: Histone methylation by the Drosophila epigenetic transcriptional regulator Ash1.
Nature. 2015.1 comment
Ivan Oransky2015 Apr 16 7:21 p.m. (2 days ago)
This is the fifth retraction by last author Frank Sauer: http://retractionwatch.com/2015/04/16/nature-retracts-epigenetics-paper-by-author-who-lost-two-science-papers-last-year/
- The breast cancer susceptibility FGFR2 provides an alternate mode of HER2 activation.
Oncogene. 2015.1 comment
Paul Brookes2015 Apr 16 11:51 a.m. (2 days ago)
Figure 5 of this paper contains images that appear more similar to each other than one would expect by coincidence.
A corresponding post. has been made at PubPeer... https://pubpeer.com/publications/BBC278257761C0C12E5D38844873DF
The journal has been notified.
- Acupuncture for chronic knee pain: a randomized clinical trial.
JAMA. 2014.6 commentsDavid Keller and Qin-hong Zhang also commented
Arthur Fan2015 Apr 16 09:12 a.m. (2 days ago)edited
The methodology flaws in Hinman’s acupuncture clinical trial, Part II: Zelen design and effectiveness dilutions: http://www.jcimjournal.com/articles/publishArticles/pdf/S2095-4964(15)60172-8.pdf
Hinman and colleagues concluded that “in patients older than 50 years with moderate or severe chronic knee pain, neither laser nor needle acupuncture conferred benefit over sham for pain or function. Our findings do not support acupuncture for these patients.” As pointed out in my former article (The methodology flaws in Hinman’s acupuncture clinical trial, Part I: Design and results interpretation. J Integr Med. 2015; 13(2): 65–68.), there were serious flaws in the trial design and statistics, as well as in the interpretation of the results. In here I address problems in the Zelen design used by them -Using Zelen design in this study does cause biases.
1 High drop-out rate:
The drop-out rates were 2.82% (2/71) in the control group; 22.86% (16/70) in the acupuncture group; 18.31% (13/71) in the laser acupuncture group; and 22.86% (16/70) for the sham laser acupuncture group. According to the acceptable standards for an RCT, dropout rates less than 10% are acceptable, drop-out rates between 10% and 20% mean that the resulting data quality is poor, and drop-out rates of more than 20% mean that the data quality is considered very poor and should not be used in analysis. In this trial analysis, the data quality in the acupuncture and sham laser acupuncture groups are very poor as the drop-out rates are over 20%; the authors should not have directly used them in any statistical analysis, unless they had re-adjusted and re-balanced the sample among the groups during the study. As outlined by the National Institutes of Health, if there is a differential drop-out rate of 15% or higher between study arms, such as between the control group and the treatment group in this clinical trial, then there is a very high potential for bias. This is a flaw that can decrease the quality of the study results.
2 The effectiveness in intervention groups was diluted by various factors
The dilution rates should then be 21.87% in the laser acupuncture group, 13.80% in the sham laser acupuncture group, and 31.27% in the acupuncture group (the dilution rate calculations were shown in Tables 1–3). The dilution rate was very significant in the acupuncture group, which causes the effectiveness to be undervalued in the acupuncture group, by almost 1/3.
The effective significance was masked by limited sample size due to the Zelen design of this study.
3.The sample size calculation in this study is questionable.Too small.
4 Conclusion
The effectiveness of the acupuncture group was diluted 31.27%, and its drop-out rate was 22.86%, much higher than that of the other groups in Hinman’s clinical trial, which constitutes major flaws in how this study is analyzed and interpreted[8]. Based on the bias of Zelen design used in the study, and incorrect sample size calculation, the conclusions drawn from this study are of poor quality, inaccurate, and invalid.
http://www.jcimjournal.com/articles/publishArticles/pdf/S2095-4964(15)60172-8.pdf
- Shorter men live longer: association of height with longevity and FOXO3 genotype in American men of Japanese ancestry.
PLoS One. 2014.1 comment
thomas samaras2015 Apr 15 8:22 p.m. (3 days ago)
Over the last few decades, many studies have supported the findings in this paper. Support has come from US, Swedish, Dutch, Italian, Okinawan, and Spanish research. A list of 45 papers, book chapters, and books are available from www.humanbodysize.com
A few papers are listed below:
Reference sources:
Samaras TT. Evidence from eight different types of studies showing that smaller body size is related to greater longevity. Journal of Scientific Research & Reports. 2014: 3 (16): 2150-2160, 2014; article no. JSRR.2014.16.003.
Samaras TT.(ed) Human Body Size and the Laws of Scaling: Physiological Performance, Growth, Longevity and Ecological Ramifications. New York: Nova Science Pub; 2007.
Salaris L, Poulain M, Samaras TT. Height and survival at older ages among men born in an inland village in Sardinia (Italy), 1866-2006. Biodemography and Social Biology, 58:1, 1-13.
Samaras,TT. Reasons to be small [Commentary] World Nutrition, March, 2011,2,3:108-135. Available at www.wphna.org.
- Short stature is associated with coronary heart disease: a systematic review of the literature and a meta-analysis.
Eur Heart J. 2010.1 comment
thomas samaras2015 Apr 15 6:49 p.m. (3 days ago)
I have studied the relationship between height, chronic diseases, and longevity for almost 40 years. One of my papers appeared in the Indian Heart Journal (2013) that summarized worldwide findings showing shorter people have inherently lower heart disease. In 2014, I had a paper published in the Journal of Scientific Research & Reports that summarized key findings showing shorter people live longer. If tall people had inherently better hearts, then why do today's taller Americans have more coronary heart disease (CHD) compared to the early 1900s when we were a few inches shorter? Also women are shorter than men and have less CHD.
Studies from the 20th C found that many populations were free of CHD and stroke. Yet, these people ranged from less than 5 feet to about 5 feet, 4 inches. These populations included Fiji, Cook Islands, Solomon Islands, Papua New Guinea, Kalahari Bushmen and the Congo pygmies. I know of no modern population that is free of CHD. Unfortunately, CHD has gone up sharply in Fiji over the last 60 years. (Major food changes and increased height have occurred over the last few decades).
In 2007, The World Cancer Research Fund reported that until recently, CHD was rare. However, in parallel with industrial development, we have seen increases in height, weight and chronic disease (which includes CHD).
Of course, both tall and short people can reach advanced ages without CHD. Many other factors are involved, such as genetics, diet, exercise, smoking, weight in relation to height, income level, etc. I found that height represents about 10% of the total longevity picture.
Unfortunately, when it comes to human health and mortality, conflicting studies abound. However, confidence in a study's findings should be based on support from different types of studies (e.g., ecological, longitudinal, cross-sectional) that provide consistent results and include populations from different parts of the world and different ethnic groups.
In 2014, a study also found that shorter people live longer (He, et al.) A 2012 study Also found shorter men lived longer (Salaris, et al.)
I have reported scores of examples showing that non-Western shorter people have less CHD than taller Westerners. See www.humanbodysize.com for a listing of over 45 papers, book chapters and books expanding on what is discussed here. Some papers and a book related to height and CHD are listed below.
Reference sources:
Samaras TT. Shorter height is related to lower cardiovascular disease risk—A narrative review. Indian Heart Journal 2013; 65: 66-71.
Samaras, TT. Is short height really a risk factor for coronary heart disease and stroke mortality? A review. Med Sci Monit 2004; 10(4): RA63-76.
Samaras TT. Evidence from eight different types of studies showing that smaller body size is related to greater longevity. Journal of Scientific Research & Reports. 2014: 3 (16): 2150-2160, 2014; article no. JSRR.2014.16.003.
Samaras TT. Human Scaling and Body Mass Index. In: Samaras TT (ed): Human Body Size and the Laws of Scaling: Physiological Performance, Growth, Longevity and Ecological Ramifications. New York: Nova Science Pub; 2007: pp 17-32.
He Q, Morris BJ, Grove JS, Petrovitch H, Ross W, Masaki KH, et al. Shorter men live longer: Association of height with longevity and FOXO3 genotype in American men of Japanese ancestry. Plos ONE 9(5): e94385. doi:10.1371/journal.pone.0094385.
Salaris L, Poulain M, Samaras TT. Height and survival at older ages among men born in an inland village in Sardinia (Italy), 1866-2006. Biodemography and Social Biology, 58:1, 1-13.
Michael Hoffman2015 Apr 15 3:27 p.m. (3 days ago) 2 of 2 people found this helpful
Correction: Segway no longer needs a computer cluster
Minor correction: since the release of Segway 1.2.0 on 29 August 2014, Segway will run on standalone computers not attached to a cluster.
- A mathematical model for the determination of total area under glucose tolerance and other metabolic curves.
Diabetes Care. 1994.1 comment
Mick Watson2015 Apr 15 11:58 a.m. (3 days ago)
The authors have simply (re)invented integration, a mathematical procedure taught to most high school students. See https://fliptomato.wordpress.com/2007/03/19/medical-researcher-discovers-integration-gets-75-citations/
- Ritual circumcision and risk of autism spectrum disorder in 0- to 9-year-old boys: national cohort study in Denmark.
J R Soc Med. 2015.1 comment
Ann Z Bauer2015 Apr 15 11:34 a.m. (3 days ago)
We commend Frisch and Simonsen on their high quality prospective cohort analysis on ritual circumcision and the risk of autism spectrum disorder (ASD) in young boys. As the authors acknowledge, and we are pleased to see, our ecologic analysis was part of the motivation behind the performance of this study. The finding in this cohort of 342,877 boys born between 1994 and 2003, that circumcised boys were more likely than intact boys to develop ASD before age 10 (HR=1.46, 95% CI: 1.11 -1.93) concurs with our study findings.Bauer AZ, 2013 It is, however, important to note that in our study we did not focus on the psychological consequences of the circumcision procedure as the causal ASD mechanism, rather we were using circumcision exposure as a proxy for the potential paracetamol (APAP, acetaminophen) exposure that may occur with the procedure. Our study aim was to explore at a population level the hypothesis of a relationship between paracetamol exposure and ASD. The authors of this study did point out that they did not have the individual data to explore this but in light of temporal rationale and new research we believe that confounding by paracetamol exposure is a plausible explanation for the observed associations and should be part of the discussion of these findings.
Temporal Rationale: The origins of circumcision predate recorded history, yet autism is considered a relatively new phenomenon, first recognized in 1943 and escalating in incidence, beginning in the 1980’s. History CDC.gov Volkmar FR, 2014 Assuming a significant portion of the recent increase in autism incidence is real, and not strictly a function of greater recognition, something about circumcision would have to have changed during this time period for it to be a significant causal factor in autism. It is difficult to contend that the psychological stress and physical pain related to circumcision has only occurred during the past 35 years. It can, however, be demonstrated that the techniques to manage this pain and stress have changed during this time period. Research beginning in the 1980’s documented the negative consequences associated with inadequate treatment of pain in children. Anand KJ, 1987 Mather L, 1983 Schechter NL, 2008 Prior to the 1990’s many procedures, including circumcision, were generally performed without analgesics. A 1994 study by Howard et al. found that when paracetamol was given regularly for at least the first 24-hour circumcision postoperative period, infants demonstrated decreased response to pain. Howard CR, 1994 This lead to the development of circumcision pain management guidelines by the American Academy of Pediatrics in 1999 suggesting procedures including the use of paracetamol. Anonymous, 1999 The International Evidence Based Group for Neonatal Pain, which included Danish researchers, published their consensus statement on newborn pain management in 2001. This statement suggests the use of paracetamol for postoperative pain including circumcision. Anand KJ, 2001 A perplexing finding in this Frisch and Simonsen Danish study is a statistically significant association between circumcision and the development of autism in the cohort of boys ages 0-4 (hazard ratio (HR)= 1.80, 95% CI 1.25-2.60) while only a very weak association for the boys ages 5-9 (HR=1.15, 95% CI 0.75-1.77). This finding can be explained by the paracetamol hypothesis. The boys that were 5-9 years of age would have been born in 1999 or prior and, based on the timing of guideline development, would likely not have been exposed to paracetamol with the procedure, while the younger boys would likely have received analgesia.
Paracetamol Research: Three prospective cohort studies have found an association between prenatal exposure to paracetamol and adverse neurodevelopment. Brandlistuen RE, 2013 Liew Z, 2014 Thompson JM, 2014 In addition, recent animal data has shown that cognition and behavior may be altered following exposure to therapeutic doses of paracetamol during early development. A recent review by de Fays et al. summaries these finding. de Fays L, 2015
To date, most neurodevelopmental research has focused on prenatal paracetamol exposure. These findings by Frisch and Simonsen and research identifying time sensitive developmental periods surrounding birth suggest the potential importance of neonate exposure. Wang SS, 2014 Although the evidence presented here is far from conclusive, paracetamol administered along with the circumcision procedure is a plausible causal mechanism for ASD that should not be dismissed and is deserving of further investigation.
- BMI and risk of dementia in two million people over two decades: a retrospective cohort study.
Lancet Diabetes Endocrinol. 2015.1 comment
Gerard Ridgway2015 Apr 15 06:39 a.m. (3 days ago) 1 of 1 people found this helpful
There is a helpful AlzForum news item on this article.
- How Does the Accuracy of Intracranial Volume Measurements Affect Normalized Brain Volumes? Sample Size Estimates Based on 966 Subjects from the HUNT MRI Cohort.
AJNR Am J Neuroradiol. 2015.1 comment
Gerard Ridgway2015 Apr 15 05:57 a.m. (3 days ago)
It's interesting to see that multi-spectral data improves agreement with manual tracings (even though the tracing used only T1-weighted images). I think this is complementary to our work showing improvements in SPM12 over older versions (Malone IB, 2015), since SPM12 can also handle multi-spectral data. For example, considering the standard deviation of the differences with respect to manual, this paper's best (lowest) single-modality result is 41.64 mL for a method based on SPM8's New Segment toolbox. We obtained a value of 35.4 mL with SPM12. With T1- and T2-weighted data, this new paper obtains an impressively low 26.7 mL, also with lower mean difference (bias) than we found. It would be interesting to know whether SPM12 can further improve results using T1-weighted and T2-weighted data.
- Genetically Determined Height and Coronary Artery Disease.
N Engl J Med. 2015.1 comment
thomas samaras2015 Apr 14 1:08 p.m. (4 days ago)edited
I have studied the relationship between height, chronic diseases, and longevity for almost 40 years. One of my papers appeared in the Indian Heart Journal (2013) that summarized worldwide findings showing shorter people have inherently lower heart disease. In 2014, I had a paper published in the Journal of Scientific Research & Reports that summarized key findings showing shorter people live longer. If tall people had inherently better hearts, then why do today's taller Americans have more coronary heart disease (CHD) compared to the early 1900s when we were a few inches shorter? Also women are shorter than men and have less CHD.
Studies from the 20th C found that many populations were free of CHD and stroke. Yet, these people ranged from less than 5 feet to about 5 feet, 4 inches. These populations included Fiji, Cook Islands, Solomon Islands, Papua New Guinea, Kalahari Bushmen and the Congo pygmies. I know of no modern population that is free of CHD. Unfortunately, CHD has gone up sharply in Fiji over the last 60 years. (Major food changes and increased height have occurred over the last few decades).
In 2007, The World Cancer Research Fund reported that until recently, CHD was rare. However, in parallel with industrial development, we have seen increases in height, weight and chronic disease (which includes CHD).
Of course, both tall and short people can reach advanced ages without CHD. Many other factors are involved, such as genetics, diet, exercise, smoking, weight in relation to height, income level, etc. I found that height represents about 10% of the total longevity picture.
Unfortunately, when it comes to human health and mortality, conflicting studies abound. However, confidence in a study's findings should be based on support from different types of studies (e.g., ecological, longitudinal, cross-sectional) that provide consistent results and include populations from different parts of the world and different ethnic groups.
I have reported scores of examples showing that non-Western shorter people have less CHD than taller Westerners. See www.humanbodysize.com for a listing of over 45 papers, book chapters and books expanding on what is discussed here. Some papers and a book related to height and CHD are listed below.
Samaras TT. Shorter height is related to lower cardiovascular disease risk—A narrative review. Indian Heart Journal 2013; 65: 66-71.
Samaras, TT. Is short height really a risk factor for coronary heart disease and stroke mortality? A review. Med Sci Monit 2004; 10(4): RA63-76.
Samaras TT. Evidence from eight different types of studies showing that smaller body size is related to greater longevity. Journal of Scientific Research & Reports 2014: 3 (16): 2150-2160, 2014; article no. JSRR.2014.16.003.
He Q, Morris BJ, Grove JS, Petrovitch H, Ross W, Masaki KH, et al. Shorter men live longer: Association of height with longevity and FOXO3 genotype in American men of Japanese ancestry. Plos ONE 9(5): e94385. doi:10.1371/journal.pone.0094385
Samaras TT. Human Scaling and Body Mass Index. In: Samaras TT (ed): Human Body Size and the Laws of Scaling: Physiological Performance,Growth, Longevity and Ecological Ramifications. New York: Nova Science Pub; 2007: pp 17-32.
Bartke A. Healthy Aging: Is smaller better?-A mini-review. Gerontology 2012; 58: 337-43.
- Rituximab for the treatment of relapses in antineutrophil cytoplasmic antibody-associated vasculitis.
Arthritis Rheumatol. 2014.1 comment
RheumJC - Rheumatology Twitter-Based Journal Club2015 Apr 14 12:56 p.m. (4 days ago) 1 of 1 people found this helpful
This article was discussed on March 3rd, 2015 by participants of #RheumJC, an international Twitter-based Rheumatology Journal Club. An engaging discussion on the science of the topic as well as the methodology of the study was had over 2 different one hour live "chats" as well as a full 24hr of asynchronous participation. Included in the second live session was the participation of the study lead author, Dr. Miloslavsky (@emilosla). Overall (combined sessions and time between and after) there were 46 total participants from 17 different countries. For the full 24 hours, there were 518 total tweets – 387 unique tweets and 117 RTs
A slide-show summary of the sessions was compiled by Lois Wingerson (@RheumatologyNet) and can be seen at http://www.rheumatologynetwork.com/vasculitis/rheumatology-journal-club-2-rituximab-aav-relapse
We would like to thank Wiley and A&R for making this manuscript open access leading up to this journal club.
Interested individuals can track and join in future journal clubs by following @RheumJC or #RheumJC, or visit the webpage at http://www.rheumjc.com and sign up for announcements.
- Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up.
Ann Rheum Dis. 2014.1 comment
RheumJC - Rheumatology Twitter-Based Journal Club2015 Apr 14 12:44 p.m. (4 days ago)
This article was discussed on January 29th, 2015 by participants of the inaugural session of #RheumJC, an international Twitter-based Rheumatology Journal Club. An engaging discussion on the science of the topic as well as the methodology of the study was had over 2 different one hour live "chats". There were 383 tweets (330 unique tweets, 53 retweets) by 38 unique participants from 5 different countries. Participants included 17 Rheumatologists, 7 Nephrologists, 6 Fellows in training/students, 1 Hospitalist, 1 Pharmacologist, and others.
A storify summary of the sessions can be seen at http://rheumjc.com/2015/01/storify-inaugural-rheumjc/
Interested individuals can track and join in future journal clubs by following @RheumJC or #RheumJC, or visit the webpage at rheumjc.com and sign up for announcements.
- Temporal structure of motor variability is dynamically regulated and predicts motor learning ability.
Nat Neurosci. 2014.2 commentsMaurice Smith also commented
Björn Brembs2015 Apr 14 06:45 a.m. (4 days ago) 5 of 6 people found this helpful
“Standing on the shoulders of giants” is what scientists say to acknowledge the work they are building on. It is a statement of humility and mostly accompanied by citations to the primary literature preceding the current work. In today’s competitive scientific enterprise, however, such humility appears completely misplaced. Instead, what many assume to be required in the struggle to survive is to convince everyone that they are the giant, the genius, the prodigy who is deserving of the research funds, the next position, tenure.
The Nature Neuroscience article “Temporal structure of motor variability is dynamically regulated and predicts motor learning ability” by Wu et al. with its accompanying news-type article “Motor variability is not noise, but grist for the learning mill” by Herzfeld and Shadmehr (linked above) can only be described as over-hyping an otherwise very interesting discovery. Both articles claim that the researchers have made the game-changing discovery that something long thought to be a bug in our movement system is actually a spectacular feature. It is argued that this discovery is such a huge surprise, because nobody in their right mind would have ever thought this “unwanted characteristic” to actually serve some purpose.
The problem with this line of argument is that probably most people in the field thought it should be obvious, even to be expected – and not surprising at all. Skinner is largely credited with the analogy of operant conditioning and evolution. This analogy entails that reward and punishment act on behaviors like selection is acting on mutations in evolution: an animal behaves variably and encounters a reward after it initiated a particular action. This reward will make the action now more likely to occur in the future, just as selection will make certain alleles more frequent in a population. Already in 1981, Skinner called this “Selection by Consequences“ (Science Vol. 213 no. 4507 pp. 501-504, DOI: 10.1126/science.7244649). Skinner’s analogy sparked wide interest, e.g. an entire journal issue (Behavioral and Brain Sciences 7(04), 1984), which later appeared in book form (The Selection of Behavior: The Operant Behaviorism of B. F. Skinner: Comments and Consequences. A. Charles Catania, Stevan R. Harnad, Cambridge University Press). Clearly, the idea that reinforcement selects from a variation of different behaviors is not a novel concept at all, but more than three decades old and rather prominent. This analogy cannot have escaped anybody working on any kind of operant/motor learning, except those seriously neglecting the most relevant literature. This interaction of variability and selection is a well-known and not overly complicated concept, based in evolutionary biology and psychology/neuroscience. Consequently, numerous laboratories have been studying various aspects of this interaction for a long time. Skinner’s projection was that increased behavioral variability leads to increased operant learning rates, just like increased mutations rates lead to increased rates of evolutionary change. More than a dozen years ago, Allen Neuringer showed this to be the case in rats (Psychonomic Bulletin & Review 2002, 9 (2), 250-258, doi: 10.3758/BF03196279), but there are studies in humans as well (Shea, J. B., & Morgan, R. B. (1979). Contextual interference effects on the acquisition, retention, and transfer of a motor skill. Journal of Experimental Psychology: Human Learning and Memory, 5, 179–187). That such variability is beneficial, rather than detrimental has been shown even in situations where the variability is so high, that the acquisition rate is reduced, but post-training performance is enhanced (Schmidt RA, Bjork RA (1992): New conceptualizations of practice: Common Principles in Three Paradigms Suggest New Concepts for training. Psychological Science, 3(4): 207-217).
Wu et al. confirm both Skinner’s conjecture as well as previously published reports (some cited above) that indeed the rate of learning in operant conditioning is increased in subjects where the initial variability in the behavior is higher. This is an important and relevant finding. However, instead of citing the wealth of earlier work, Wu et al. claim that their results were surprising: “Surprisingly, we found that higher levels of task-relevant motor variability predicted faster learning”. Herzfeld and Shadmehr were similarly stunned: “These results provide intriguing evidence that some of the motor variability commonly attributed to unwanted noise is in fact exploration in motor command space.”
I regard it as highly unlikely that none of the seven authors in total should have never heard of Skinner or the work over the last four decades by many human movement scientists that have explored the temporal structure of human movement variability and its relationship with motor learning. The work by senior scientists such as Karl Newell, Michael Turvey, Richard Schmidt, and their students published in books and hundreds of journal articles is completely ignored, just as the work by several younger mid-career scientists such as Nick Stergiou, Jeff Hausdorff, Thurmon Lockhart, Didier Dilignieres, and many others. After a thorough review of this literature the authors may realize that some of their results are neither new nor novel. If indeed the authors were unaware of this entire section of literature so relevant to their own research, it would be an indictment in its own right.
It needs to be emphasized explicitly, that the above does not call into question the validity of the research results, nor does it imply that the described results do not merit publication. Clearly, the research described in Wu et al. is relevant, interesting and it was absolutely correct to publish it in its entirety. What ought to have happened, however, is to encourage the authors to include the relevant references in the appropriate sections of their articles.
(Much of this comment was drafted together with Dr. Nick Stergiou)
- A Novel Dual Ex Vivo Lung Perfusion Technique Improves Immediate Outcomes in an Experimental Model of Lung Transplantation.
Am J Transplant. 2015.1 comment
M. Mohamed2015 Apr 14 01:59 a.m. (4 days ago)
Though this paper provides experimental data about the dual EVLP. A similar system was described 6 months before the publication of this paper as a part of a theoretically introduced Shehata EVLP system and protocol. http://garj.org/garjmms/pdf/2014/October/Mohamed..pdf
- Vascular endothelial growth factor C promotes breast cancer progression via a novel antioxidant mechanism that involves regulation of superoxide dismutase 3.
Breast Cancer Res. 2014.1 comment
FREDERICK DOMANN2015 Apr 13 11:39 p.m. (4 days ago)
For prior work related to SOD3 and EcSOD in breast cancer please see the following:
- Structural Plasticity of the Hippocampus and Amygdala Induced by Electroconvulsive Therapy in Major Depression.
Biol Psychiatry. 2015.1 comment
Joe Newton2015 Apr 13 2:16 p.m. (5 days ago)
Major depression diagnosis in the absence of preexisting biomarkers is uncertain and a dilemma of psychiatry. However, measurable biomarkers of intracranial volumes are suggested by the large genetic and imaging consortium studies. (Stein JL, et al. 2012 Nat Genet. Apr 15;44(5):552-61). Nevertheless your paper is unusually interesting in suggesting ECT induced hippocampal volumes.
I have wondered for decades about how ECT improves nervous system coordination in a broad spectrum of abnormal behavioral responses.
Best wishes, Joe Ray Newton
Top comments now - more about this
Lin A.J Neurosci. 2015.1 comment
Dorothy V M Bishop2015 Apr 18 04:07 a.m. (19 hours ago) 2 of 2 people found this helpful
This is an impressive paper in terms of sample size for those with aneuploidies, and the results are intriguing and important. It is particularly surprising that the asymmetries in the XXY group look so normal, when –as the authors point out - the one functional study on this group found strikingly reduced functional asymmetry in the Superior Temporal Gyrus (van Rijn et al, 2008). As the authors note, the links between functional and structural asymmetries are far from clear, and this study provides further motivation for doing studies that contrast the two.
I have just one niggling criticism, which is that the authors cite Sun et al as evidence for early asymmetric gene expression in humans. I don't think that the data from Sun et al support their conclusions, and I've explained why in a comment on PubMed Commons. http://www.ncbi.nlm.nih.gov/pubmed?term=Early asymmetry of gene transcription in embryonic human left and right cerebral cortex
Guadalupe T.Cortex. 2015.1 comment
Dorothy V M Bishop2015 Apr 18 12:12 p.m. (11 hours ago) 2 of 2 people found this helpful
The literature on sex differences in cerebral asymmetry does appear to be very confusing, and this paper does a thorough job in attempting to address the inconsistencies. I'm not sure it completely resolves the issue, but it sets a high methodological standard by using much larger sample sizes than previous studies and including two replication samples. It also includes a genetic analysis, which I won't discuss here.
Structural asymmetry of the planum temporale, with larger PT on the left, was described 47 years ago by Geschwind and Levitsky. Since that time it has become clear that the proportion of the population showing asymmetry varies substantially according to how it is measured. There have been claims of sex differences in PT asymmetry, but, as noted by Guadalupe et al, there have also been counterclaims, and a recent meta-analysis concluded that there is no sex difference, and the impression of one arose because of publication bias.
Guadalupe et al, however, found a reliable sex difference in PT asymmetry that replicates across three samples. However, their method of measurement does have one characteristic that I found puzzling: in a sample of 2337 adults they found nobody with reversed asymmetry (i.e., R>L planum). This contrasts with the original sample of Geschwind and Levitsky, where 11% had reversed asymmetry, and 24% had equal size PT on left and right. G&L's study was based on examination of post mortem specimens, but Watkins et al (2001) found similar proportions in a voxel-based analysis of grey matter from 142 MRI scans.
I assume the finding of universal left-biased PT in the current study had to do with the method by which this was defined: this was different from the method used by Watkins et al.
In the current study, grey matter was quantified in cortical regions based on a template taken from a average brain, then weighting each voxel by the probability that it belonged to that specific cortical region. The authors note that there are regional asymmetries in the atlas they used that will necessarily influence the mean – presumably, the left planum map is bigger than the right planum map, and so there are more voxels to count on the left. The authors argue that we already know that the left and right perisylvian regions differ systematically in their anatomy on average, and the interest here is in individual differences. They argued therefore that an averaged left-right template would not capture the systematic differences between the two sides.
I have trouble understanding how the template they used could adequately capture cases where someone had a larger than average PT. If the template represents the PT from an average brain, there will be variation around that average, with some people have larger and others having smaller PTs. If voxels were counted if they were within the template and not otherwise, anyone who had a PT that actually extended beyond the template would not have all their voxels counted. I appreciate that in practice, a more sophisticated probabilistic approach was used, but I'm not sure this would solve the problem. The template is based on 37 brains; we know that around 11% of people have R>L planum temporale, so around 3-4 contributors to the template would have that pattern. So, if I understand it correctly, voxels in the outskirts of a core region would have a low weighting, because in only a small proportion of the template subjects would this region be included in PT. But this means that for a new subject who genuinely had PT in that region, the amuont of grey matter in PT would be underestimated, because the weighting would be low. And there may be some people with rare PT configurations who may have parts of their PT not represented at all in the template. In this regard, given the known individual variation in PT, 37 people seems rather small a number on which to base probabilistic weightings.
I wondered whether this aspects of methodology explained why the volume measures for the Freesurfer analysis had standard deviations that were about 1.7 times as large as the standard deviations for the HO atlas analysis – is the HO atlas analysis in effect minimising or excluding values for those whose PTs are more extensive than the average?
I can't see an obvious reason why this should generate spurious sex differences, but I wondered if it could explain the absence of cases of reversed asymmetry in this sample.
Overall, I thank the authors for providing such comprehensive data on this vexed topic; it is remarkable how the measurement of asymmetry, which looks on the surface like such a simple issue, is exceedingly complex, with specific analytic choices leading to different patterns of findings. It is good to see examples like this where alternative approaches are used to give one the opportunity to observe their effects.
Geschwind, N., & Levitsky, W. (1968). Human brain: left-right asymmetries in temporal speech region. Science, 161, 186-187. Watkins, K. E., Paus, T., Lerch, J. P., Zijdenbos, A., Collins, D. L., Neelin, P., . . . Evans, A. C. (2001). Structural asymmetries in the human brain: a voxel-based statistical analysis of 142 MRI scans. Cerebral Cortex, 11, 868-877.
Wu HG.Nat Neurosci. 2014.2 comments
In reply to a comment by Björn Brembs2015 Apr 14 06:45 a.m. (4 days ago)
Maurice Smith2015 Apr 18 4:27 p.m. (6 hours ago)edited 2 of 2 people found this helpful
We agree with the sentiment conveyed by the above comment, that overhyping scientific results is a problem. We do not, however, think that Dr. Brembs is on solid ground with his various charges about our paper (Wu et al. 2014). It is, of course, the specifics that matter. And the specific charges made in the above comment and various blog posts authored by Dr. Brembs lack any nuance and end up being rather misleading. What follows is an attempt to clarify the record.
Reading the introduction section of our paper should provide a direct counter to Dr. Brembs main charge that we fail to acknowledge previous work on reinforcement learning. Nearly 40% of our paper’s introduction (the entirety of paragraphs 3-4), where we lay out the motivation for our study, is devoted to a discussion of previous work about the idea that motor variability might enhance motor learning ability. We specifically acknowledge that this idea comes from both reinforcement learning theory (2 citations, #16-17) and motor learning studies in animals (6 additional citations: 4 in songbirds, #12-15, 2 in rodents, #18-19). While we did not cite the particular references mentioned in Dr. Brembs’ comment, we argue that the studies we do cite are more germane and cover essentially the same ground. We are as big fans of Skinner as is Dr. Brembs, but the Wu et al. (2014) paper is not a historic review on operant conditioning and reinforcement learning. When faced with a strict journal policy citation limit (50 for the whole paper), one cannot appropriately cover the intellectual history of an entire field, which is why we cited a book and a review where the interested reader can get this information (and yes, Skinner is cited there). We believe the citations we included are appropriate for readers to meaningfully appreciate the context of our study in relation to key previous ideas and scientific work.
Dr Brembs’ suggestion that we overhype our results by suggesting that they are “surprising” is taken completely out of context, as the quote he uses cuts out key information from the very sentence it comes from. The full sentence referred to in his comment reads: “Surprisingly, we found that higher levels of task-relevant motor variability predicted faster learning BOTH across individuals AND across tasks in TWO different paradigms, one relying on REWARD-BASED learning to shape specific arm movement trajectories and the other relying on ERROR-BASED LEARNING to adapt movements in novel physical environments.” (emphasis added here). Here the word “surprisingly” clearly refers to the constellation of our findings, which in our view, and the view of our paper’s peer reviewers, is indeed surprising and novel. This is in sharp contrast to the out-of-context extraction of the first phrase in Dr. Brembs’ comments: “Surprisingly, we found that higher levels of task-relevant motor variability predicted faster learning,” which misconstrues the meaning of the sentence.
Regarding the specific citations that Dr. Brembs suggest we inappropriately left out (Neuringer 2002, Shea & Morgan 1979, Schmidt & Bjork 1992), a close examination reveals that these citations are for findings that are either disputed or not very relevant. The Neuringer (2002) study in rats used variability as an operant to experimentally induce different levels of variability. However, there are several confounds as well as methodological and interpretive difficulties with these experiments, making it very difficult to draw any conclusions regarding the relationship between the structure of normally expressed trial-to-trial motor variability and learning ability. These various issues are discussed in subsequent papers that aimed to replicate Neuringer’s finding (see Maes and van der Goot, Learning and Motivation 2006 and Doolan and Bizo, The Psychological Record, 2013). These studies, conducted in humans and hence more relevant to our findings, could not replicate Neuringer’s result. In fact, both showed an opposite effect, i.e. going against what Skinner and reinforcement learning theory would have predicted.
The Shea & Morgan (1979) and Schmidt & Bjork (1992) studies, which Dr. Brembs also claims are similar to ours, are perhaps even less relevant. These studies are squarely about what has been termed “contextual interference”, i.e. effects that arise when switching between tasks when multiple different tasks are trained in an interspersed fashion. These studies have nothing to do with trial-to-trial variability, but variability in task structure. We, in contrast, studied learning within a single task, precluding any such interference effects. If one were to compare the findings from these papers to our study in an “apples to apples” manner, and we strongly believe that one should not, they would predict the opposite of our results. In the contextual interference studies, the benefit of interspersed training is not seen in the initial learning rate. In fact, the initial learning rate is markedly decreased (in line with the moniker “contextual interference”), exactly the opposite of what we report. Again, this difference is not surprising given how different the studies are. The benefit in learning seen with contextual interference is in the long-term retention, an issue that we did not investigate at all in Wu et al 2014. As a primary research paper with strict limits on the number of words and citations, ours cannot be expected to be a scholarly review of various tangential studies.
Finally, it should also be noted that Dr. Brembs’ comment refers to a small fraction of our paper’s content, and as such any protracted discussion of the pertaining results would have been at the expense of discussion points relating to other findings, which Dr. Brembs himself found more interesting. We can reassure the reader that it was very painful to cut down the discussion, introduction, and citations to conform to Nature Neuroscience’s strict and rather arbitrary limits. We would personally be in favor of expanding these limits, or doing away with them entirely, but this is not our choice to make. Given these constraints, we are comfortable with the choices we made and do not agree that they misrepresent the context or novelty of our findings.