Chronic Traumatic Encephalopathy in Contact Sports: A Systematic Review of All Reported Pathological Cases

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with head trauma. Although initially believed to affect only boxers, the at-risk population has expanded to encompass a much wider demographic, including American football players, hockey players, wrestlers, and military veterans. This expansion has garnered considerable media attention and public concern for the potential neurodegenerative effects of head trauma. The main aim of this systematic review is to give a complete overview of the common findings and risk factors for CTE as well as the status quo regarding the incidence and prevalence of CTE. This systematic review was performed using PubMed and MEDLINE and includes all neuropathologically confirmed cases of CTE in the medical literature to date, from the first published case in 1954 to August 1, 2013 (n = 153). The demographics, including the primary source of mTBI (mild Traumatic Brain Injury), age and cause of death, ApoE genotype, and history of substance abuse, when listed, were obtained from each case report. The demographics of American football players found to have CTE are also presented separately in order to highlight the most prevalent group of CTE cases reported in recent years. These 153 case reports of CTE represent the largest collection to date. We found that a history of mTBI was the only risk factor consistently associated with CTE. In addition, we found no relationships between CTE and age of death or abnormal ApoE allele. Suicide and the presence of premorbid dementia was not strongly associated with CTE. We conclude that the incidence of CTE remains unknown due to the lack of large, longitudinal studies. Furthermore, the neuropathological and clinical findings related to CTE overlap with many common neurodegenerative diseases. Our review reveals significant limitations of the current CTE case reporting and questions the widespread existence of CTE in contact sports.     

Computers a cornerstone of evidence-based care,conference told.

Computers are poised to become key players in the delivery of health care, but are physicians ready for them? A recent conference on medical communication in the electronic era examined the potential of computers to assist in diagnosis, provide continuing medical education, disseminate evidence and research findings, and simplify practice management. However, delegates were told that even though many medical practices are computerized, it is often staff members and not physicians who use the technology. For computers to gain wider acceptance for medical purposes, physicians need to be made comfortable with their use at an early stage of training.     

Interpersonal coordination analysis of tennis players from different levels during official matches

The purpose of this study was to assess the interpersonal coordination during official male tennis matches in players of different skill levels. Players’ trajectories of three levels (Juvenile, ATP-Future, ATP-250) were obtained using video-based tracking system. A vector coding technique was applied to obtain players’ interpersonal coordination in four coordination patterns: “anti-phase”, “in-phase”, “serving player phase” and “returning player phase”. These patterns allowed identification of the nature of the coupling and lead/lag relations between players. In all categories, players presented higher degree of “anti-phase” and “serving player phase” (when only the serving player is moving on the court or his opponent is moving with a time lag) coordination. Young players spent more time in “serving player phase” during lateral displacements than professional players. On the other hand, professional players spent more time in “returning player phase” (when only the returning player is moving on the court or his opponent is moving with a time lag) during antero posterior displacements, than young players. Interpersonal coordination did not change from the first to the second set of the match, showing that tennis players maintain their displacement characteristics and strategy, independently of proficiency level. The vector coding technique allowed to identify new coordination patterns in tennis, providing additional information about tennis dynamics and how players from different categories and proficiency levels behave during the matches.     

A critique of the “ultra‐high risk” and “transition” paradigm

The transdiagnostic expression of psychotic experiences in common mental disorder (anxiety/depression/substance use disorder) is associated with a poorer prognosis, and a small minority of people may indeed develop a clinical picture that meets criteria for schizophrenia. However, it appears neither useful nor valid to observe early states of multidimensional psychopathology in young people through the “schizo”‐prism, and apply misleadingly simple, unnecessary and inefficient binary concepts of “risk” and “transition”. A review of the “ultra‐high risk” (UHR) or “clinical high risk” (CHR) literature indicates that UHR/CHR samples are highly heterogeneous and represent individuals diagnosed with common mental disorder (anxiety/depression/substance use disorder) and a degree of psychotic experiences. Epidemiological research has shown that psychotic experiences are a (possibly non‐causal) marker of the severity of multidimensional psychopathology, driving poor outcome, yet notions of “risk” and “transition” in UHR/CHR research are restrictively defined on the basis of positive psychotic phenomena alone, ignoring how baseline differences in multidimensional psychopathology may differentially impact course and outcome. The concepts of “risk” and “transition” in UHR/CHR research are measured on the same dimensional scale, yet are used to produce artificial diagnostic shifts. In fact, “transition” in UHR/CHR research occurs mainly as a function of variable sample enrichment strategies rather than the UHR/CHR “criteria” themselves. Furthermore, transition rates in UHR/CHR research are inflated as they do not exclude false positives associated with the natural fluctuation of dimensional expression of psychosis. Biological associations with “transition” thus likely represent false positive findings, as was the initial claim of strong effects of omega‐3 polyunsatured fatty acids in UHR samples. A large body of UHR/CHR intervention research has focused on the questionable outcome of “transition”, which shows lack of correlation with functional outcome. It may be more productive to consider the full range of person‐specific psychopathology in all young individuals who seek help for mental health problems, instead of “policing” youngsters for the transdiagnostic dimension of psychosis. Instead of the relatively inefficient medical high‐risk approach, a public health perspective, focusing on improved access to a low‐stigma, high‐hope, small scale and youth‐specific environment with acceptable language and interventions may represent a more useful and efficient strategy.     

Role of glycosylation of Notch in development

The Notch pathway is one of the major signaling pathways required for proper development in metazoans. Notch activity is regulated at numerous levels, and increasing evidence reveals the importance of “protein glycosylation” (modification of Notch receptors with sugars) for its regulation. In this review we summarize the significance of the Notch pathway in development and the players responsible for its glycosylation, and then discuss the molecular mechanisms by which protein glycosylation may regulate Notch function.     

Do Permanent Night Workers Show Circadian Adjustment? A Review Based on the Endogenous Melatonin Rhythm

“Permanent” or “fixed” night shifts have been argued to offer a potential benefit over rotating shift systems in that they may serve to maximize circadian adjustment and hence minimize the various health and safety problems associated with night work. For this reason, some authors have argued in favor of permanent shift systems, but their arguments assume at least a substantial, if not complete, adjustment of the circadian clock. They have emphasized the finding that the day sleeps taken between successive night shifts by permanent night workers are rather longer than those of either slowly or rapidly rotating shift workers, but this could simply reflect increased pressure for sleep. The present paper reviews the literature on the adjustment to permanent night work of the circadian rhythm in the secretion of melatonin, which is generally considered to be the best known indicator of the state of the endogenous circadian body clock. Studies of workers in “abnormal” environments, such as oil rigs and remote mining operations, were excluded, as the nature of these unique settings might serve to assist adjustment. The results of the six studies included indicate that only a very small minority (<3%) of permanent night workers evidence “complete” adjustment of their endogenous melatonin rhythm to night work, less than one in four permanent night workers evidence sufficiently “substantial” adjustment to derive any benefit from it, there is no difference between studies conducted in normal or dim lighting, and there is no evidence of gender difference in the adjustment to permanent night work. It is concluded that in normal environments, permanent night‐shift systems are unlikely to result in sufficient circadian adjustment in most individuals to benefit health and safety.     

A Critical Review of the Traditional Methodology of Cost-Benefit Analysis and a Proposed Alternative

“Risk management” is essential to the decision-making process that prescribes regulations for protecting human health. As a comprehensive decision-making approach, risk management encompasses risk assessment, risk perception, economic factors, and their respective uncertainties. Cost-benefit analysis (CBA) has long been the preferred methodology for evaluating the economic factors associated with such regulations. Within this context, CBA confirms whether or not the “benefit” of a given regulatory option is greater than its “cost.” This article proposes an alternative CBA methodology whose guiding concept is the “optimization” of outcomes for the stakeholders in regulations that aim to protect human health. This article further proposes evaluation criteria for CBA and critiques the traditional and alternative variants against this standard, ultimately to demonstrate the superiority of the latter.     

Reconciling “stress” and “health” in physical anthropology: What can bioarchaeologists learn from the other subdisciplines?

The concepts of “stress” and “health” are foundational in physical anthropology as guidelines for interpreting human behavior and biocultural adaptation in the past and present. Though related, stress and health are not coterminous, and while the term “health” encompasses some aspects of “stress,” health refers to a more holistic condition beyond just physiological disruption, and is of considerable significance in contributing to anthropologists' understanding of humanity's lived experiences. Bioarchaeological interpretations of human health generally are made from datasets consisting of skeletal markers of stress, markers that result from (chronic) physiological disruption (e.g., porotic hyperostosis; linear enamel hypoplasia). Non-specific indicators of stress may measure episodes of stress and indicate that infection, disease, or nutritional deficiencies were present in a population, but in assessing these markers, bioarchaeologists are not measuring “health” in the same way as are human biologists, medical anthropologists, or primatologists. Rather than continue to diverge on separate (albeit parallel) trajectories, bioarchaeologists are advised to pursue interlinkages with other subfields within physical anthropology toward bridging “stress” and “health.” The papers in this special symposium set include bioarchaeologists, human biologists, molecular anthropologists, and primatologists whose research develops this link between the concepts of “stress” and “health,” encouraging new avenues for bioarchaeologists to consider and reconsider health in past human populations. Am J Phys Anthropol 155:181–185, 2014. © 2014 Wiley Periodicals, Inc.     

Chronotype,gender and general health

Background: Light–dark alternation has always been the strongest external circadian “zeitgeber” for humans. Due to its growing technological preference, our society is quickly transforming toward a progressive “eveningness” (E), with consequences on personal circadian preference (chronotype), depending on gender as well. The aim of this study was to review the available evidence of possible relationships between chronotype and gender, with relevance on disturbances that could negatively impact general health, including daily life aspects. Methods: Electronic searches of the published literature were performed in the databases MEDLINE and Web of Science, by using the Medical Subject Heading (MeSH), when available, or other specific keywords. Results: Results were grouped into four general areas, i.e. (a) “General and Cardiovascular Issues”, (b) “Psychological and Psychopathological Issues”, (c) “Sleep and Sleep-Related Issues” and (d) “School and School-Related Issues”. (a) E is associated with unhealthy and dietary habits, smoking and alcohol drinking (in younger subjects) and, in adults, with diabetes and metabolic syndrome; (b) E is associated with impulsivity and anger, depression, anxiety disorders and nightmares (especially in women), risk taking behavior, use of alcohol, coffee and stimulants, psychopathology and personality traits; (c) E has been associated, especially in young subjects, with later bedtime and wake-up time, irregular sleep–wake schedule, subjective poor sleep, school performance and motivation, health-related quality of life; (d) E was associated with lowest mood and lower overall grade point average (especially for women). Conclusions: Eveningness may impact general health, either physical or mental, sleep, school results and achievements, especially in younger age and in women. The role of family support is crucial, and parents should be deeply informed that abuse of technological devices during night hours may lead to the immature adjustment function of children’s endogenous circadian pacemakers.     

How to make stone soup: Is the “Paleo diet” a missed opportunity for anthropologists?

For the past few years, people everywhere have been “going Paleo.” Websites and social media touting the benefits of eating a “Paleo diet” and following a “Paleolithic life style” serve as calls to arms for health‐conscious individuals seeking information about the latest health and fitness trends. Many of these people participate in programs such as Crossfit, which involve major social and life‐style modification components and therefore facilitate the dissemination of dietary fads.¹ The PALEOf(x)^TM conference, which bills itself as “the world's premier holistic wellness event,” has attracted sellout crowds of thousands of attendees for the last four years.² Consumers can wear Paleo clothing, download Paleo shopping and exercise apps to their smartphones, order prepackaged Paleo food, prepare it using Paleo cooking implements, or expediently buy Paleo convenience foods from Paleodiet? vending machines³ and “Cultured Caveman” food trucks.⁴ The Paleo diet is touted by movie stars, reality TV personalities, and professional athletes, including LeBron James and the entire Miami Dolphins NFL team.^5,6 Books with titles such as The Primal Blueprint,⁷ Cavewomen Don't Get Fat,⁸ and Paleo Perfected⁹ (the latter by the stodgy America's Test Kitchen) are legion, and many are bestsellers.     

Phylogenetic comparative methods: Harnessing the power of species diversity to investigate welfare issues in captive wild animals

This paper reviews a way of investigating health and welfare problems in captive wild animals (e.g., those in zoos, aviaries, aquaria, or aquaculture systems) that has great potential, but to date has been little used: systematically comparing species with few or no health and welfare issues to those more prone to problems. Doing so empirically pinpoints species‐typical welfare risk and protective factors (such as aspects of their natural behavioral biology): information which can then be used to help prevent or remedy problems by suggesting new ways to improve housing and husbandry, and by identifying species intrinsically best suited to captivity. We provide a detailed, step‐by‐step “how to” guide for researchers interested in using these techniques, including guidance on how to statistically control for the inherent similarities shared by related species: an important concern because simple, cross‐species comparisons that do not do this may well fail to meet statistical assumptions of non‐independence. The few relevant studies that have investigated captive wild animals’ welfare problems using this method are described. Overall, such approaches reap value from the great number and diversity of species held in captivity (e.g., the many thousands of species held in zoos); can yield new insights from existing data and published results; render previously intractable welfare questions (such as “do birds need to fly?” or “do Carnivora need to hunt?”) amenable to study; and generate evidence‐based principles for integrating animal welfare into collection planning.     

When will evolution lead to deceptive signaling in the Sir Philip Sidney game?

Sir Philip Sidney games are a widely used model of simple signaling. Johnstone and Grafen [Johnstone, R.A., Grafen, A., 1993. Dishonesty and the handicap principle. Animal Behaviour 46, 759–764] present a version in which the Evolutionarily Stable Strategy (ESS) is for most signalers to “honestly” signal, with a small minority of signalers who “cheat”. This model is among the most frequently cited papers on the topic of “dishonest” signaling and supports the view that signals may be “dishonest” as long as they are “honest on average”. Using genetic algorithms, we demonstrate that another solution exists to the game, an evolutionarily stable set of Nash equilibria in which members of the set never signal and all donors give their resource. Payoffs to players using this set of strategies is greater those when playing the “dishonest” signaling ESS. We demonstrate that a random population is far more likely to evolve to this non-communicating strategy set than the “dishonest” signaling ESS. We also discuss the dynamics of biological game theory models and the advances of genetic algorithms as a heuristic solution method for these models.     

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: A Neuroendocrine Approach to Patients With Traumatic Brain Injury

Objective: Traumatic brain injury (TBI) is now recognized as a major public health concern in the United States and is associated with substantial morbidity and mortality in both children and adults. Several lines of evidence indicate that TBI-induced hypopituitarism is not infrequent in TBI survivors and may contribute to the burden of illness in this population. The goal of this article is to review the published data and propose an approach for the neuroendocrine evaluation and management of these patients.Methods: To identify pertinent articles, electronic literature searches were conducted using the following keywords: “traumatic brain injury,” “pituitary,” “hypopituitarism,” “growth hormone deficiency,” “hypogonadism,” “hypoadrenalism,” and “hypothyroidism.” Relevant articles were identified and considered for inclusion in the present article.Results: TBI-induced hypopituitarism appears to be more common in patients with severe TBI. However, patients with mild TBI or those with repeated, sports-, or blast-related TBI are also at risk for hypopituitarism. Deficiencies of growth hormone and gonadotropins appear to be most common and have been associated with increased morbidity in this population. A systematic approach is advised in order to establish the presence of pituitary hormone deficiencies and implement appropriate replacement therapies.Conclusion: The presence of traumatic hypopituitarism should be considered during the acute phase as well as during the rehabilitation phase of patients with TBI. All patients with moderate to severe TBI require evaluation of pituitary function. In addition, symptomatic patients with mild TBI and impaired quality of life are at risk for hypopituitarism and should be offered neuroendocrine testing.Abbreviations: CBG = corticosteroid-binding globulin DI = diabetes insipidus GH = growth hormone IGF-1 = insulin-like growth factor 1 SIADH = syndrome of inappropriate antidiuretic hormone T₄ = thyroxine TBI = traumatic brain injury TSH = thyroid-stimulating hormone     

The NFL combine: does it predict performance in the National Football League?

The authors investigate the correlation between National Football League (NFL) combine test results and NFL success for players drafted at three different offensive positions (quarterback, running back, and wide receiver) during a recent 6-year period, 1999-2004. The combine consists of series of drills, exercises, interviews, aptitude tests, and physical exams designed to assess the skills of promising college football players and to predict their performance in the NFL. Combine measures examined in this study include 10-, 20-, and 40-yard dashes, bench press, vertical jump, broad jump, 20- and 60-yard shuttles, three-cone drill, and the Wonderlic Personnel Test. Performance criteria include 10 variables: draft order; 3 years each of salary received and games played; and position-specific data. Using correlation analysis, we find no consistent statistical relationship between combine tests and professional football performance, with the notable exception of sprint tests for running backs. We put forth possible explanations for the general lack of statistical relations detected, and, consequently, we question the overall usefulness of the combine. We also offer suggestions for improving the prediction of success in the NFL, primarily the use of more rigorous psychological tests and the examination of collegiate performance as a job sample test. Finally, from a practical standpoint, the results of the study should encourage NFL team personnel to reevaluate the usefulness of the combine's physical tests and exercises as predictors of player performance. This study should encourage team personnel to consider the weighting and importance of various combine measures and the potential benefits of overhauling the combine process, with the goal of creating a more valid system for predicting player success.     

Is the “Ecological Fallacy” a Fallacy?

Ecological studies of health effects due to agent exposure are generally considered to be a blunt instrument of scientific investigation, unfit to determine the “true” exposure-effect relationship for an agent. Based on this widely accepted tenet, ecological studies of the correlation between the local air concentration of radon and the local lung cancer mortality as measured by Cohen have been criticized as being subject to the “Ecological Fallacy” and thus producing invalid risk data. Here we discuss the data that a risk assessment needs as a minimum requirement for making a valid risk estimate. The examination of these data and a “thought experiment” show that it is Cohen's raw ecological data, uncorrected for population characteristic factors, which are the proper data for a risk assessment. Consequently, the “true” exposure-effect relationship is less and less important the more population characteristic factors are identified and the larger they are. This reversal of the usual argument is due to our approach: Here, the prediction of the health effects in an exposed population is of primary importance, not the shape of the “true” exposure-effect relationship. The results derived in this paper hold for ecological studies of any agent causing any health or other effect.     

Beyond the “at risk mental state” concept: transitioning to transdiagnostic psychiatry

The “at risk mental state” for psychosis approach has been a catalytic, highly productive research paradigm over the last 25 years. In this paper we review that paradigm and summarize its key lessons, which include the valence of this phenotype for future psychosis outcomes, but also for comorbid, persistent or incident non‐psychotic disorders; and the evidence that onset of psychotic disorder can at least be delayed in ultra high risk (UHR) patients, and that some full‐threshold psychotic disorder may emerge from risk states not captured by UHR criteria. The paradigm has also illuminated risk factors and mechanisms involved in psychosis onset. However, findings from this and related paradigms indicate the need to develop new identification and diagnostic strategies. These findings include the high prevalence and impact of mental disorders in young people, the limitations of current diagnostic systems and risk identification approaches, the diffuse and unstable symptom patterns in early stages, and their pluripotent, transdiagnostic trajectories. The approach we have recently adopted has been guided by the clinical staging model and adapts the original “at risk mental state” approach to encompass a broader range of inputs and output target syndromes. This approach is supported by a number of novel modelling and prediction strategies that acknowledge and reflect the dynamic nature of psychopathology, such as dynamical systems theory, network theory, and joint modelling. Importantly, a broader transdiagnostic approach and enhancing specific prediction (profiling or increasing precision) can be achieved concurrently. A holistic strategy can be developed that applies these new prediction approaches, as well as machine learning and iterative probabilistic multimodal models, to a blend of subjective psychological data, physical disturbances (e.g., EEG measures) and biomarkers (e.g., neuroinflammation, neural network abnormalities) acquired through fine‐grained sequential or longitudinal assessments. This strategy could ultimately enhance our understanding and ability to predict the onset, early course and evolution of mental ill health, further opening pathways for preventive interventions.     

Body size and composition of National Football League players

The purpose of this study was to present a profile of body size and composition of National Football League (NFL) players prior to the start of the regular season. Fifty-three members of the Indianapolis Colts professional football team were measured for height, body mass, and percentage body fat using the BOD POD air-displacement plethysmography system during summer camp of the 2003 football season. These data were categorized by position for comparison with previous studies of NFL football players. The relationships observed were as follows (= represents nonsignificant; > represents p < or = 0.05): Height: Offensive Line = Defensive Line = Quarterbacks/Kickers/Punters = Tight Ends > Linebackers > Running Backs = Wide Receivers = Defensive Backs. Body Mass: Offensive Line = Defensive Line > Tight Ends = Linebackers > Running Backs = Quarterbacks/ Kickers/Punters > Wide Receivers = Defensive Backs. Percentage Body Fat: Offensive Line > Defensive Line > Quarterbacks/ Kickers/Punters = Linebackers = Tight Ends > Running Backs = Wide Receivers = Defensive Backs. Comparisons to teams in the 1970s indicate that body mass has increased only for offensive and defensive linemen; however, height and body fat among player positions have not dramatically changed. Furthermore, the body mass index is not an accurate measure or representation of body fat or obesity in NFL players. These data provide a basic template for size profiles and differences among various positions and allow comparisons with other studies for changes in the NFL over the past 3 decades.     

Comparison of the increase in body size between 1899 and 1970 in a specially selected group with that in the general population

Height and weight data for varsity football players from 1899 to 1970 were analyzed for evidence of a secular trend in such a specialized sample. Recent football teams ('61–'70) are, on the average, 2.6 inches (6.6 cm) taller and 35.3 pounds (16.05 kg) heavier than the teams at the turn of the century (1899–1910). The estimated trend over the 70 year span was 0.37 inches (0.94 cm) per decade for stature and 5.04 pounds (2.29 kg) per decade for weight. Unfortunately, it is not possible to partition these trends and obtain separate estimates for the “secular” effects and for those effects that might be attributed to “recruiting practices.” The observed trend for stature in football players corresponds with the upper limit of the estimated range for adult secular trend data for stature from Western European countries, and is greater than that reported for American young adult males both in college and in the general population.     

Risky cultures to risky genes: The racialised discursive construction of south Asian genetic diabetes risk

Type 2 diabetes within UK South Asian populations has increasingly become the focus of health science discourse. Growing rates across the globe have been a public health concern for a number of decades. Diabetes discourse has focused on lifestyle and a generalized idea of “cultural” factors as contributory factors. These have become part of what I identify as a South Asian diabetes “risk-package.” This risk formulation is extended to an additional genetic discourse which generates new causal explanations for this heightened “risk.” South Asian groups are already the subject of discursive, racialized risk constructions, which positions them as active owners of “risky culture.” The mobilization of genetic arguments repositions them as additionally passive owners of “risky genes.” I argue that the use of racial categories in genetic diabetes science, despite the relative uncertainty and ambiguity of scientific knowledge claims, is problematic and requires critical re-situating.     

Animal Welfare Beyond the Cage … and Beyond the Evidence?

In “Laboratory Rodent Welfare: Thinking Outside the Cage,” Balcombe (2010/this issue) suggests that laboratory cage housing is damaging to rats and mice because it does not meet their evolved needs and may damage their psychological and physical health. The article also indicates that larger and more enriched spaces reduce aggression and mortality and improve the health and friendliness of rodents in the laboratory. Remarkably, many of the studies cited as supporting these assertions fail to provide data bearing on the issues involved or may even report findings opposite to those described by Balcombe, whereas many studies that are highly relevant to these issues are not cited or described. Moreover, although the “evolved needs” of rats and mice are presented as the basis for an analysis of rodent welfare, the important and well-documented changes in needs- or motivation-related behaviors of a rodent in the laboratory (due to human selection over hundreds of generations) is ignored. This pattern of disconnections between data and conclusions is so pervasive as to demolish the scientific value of the exposition.