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Background/aimTo evaluate the association of genetic polymorphisms APOE,APOEG-219T promoter, microtubule associated protein(MAPT)/tauexon 6 Ser53Pro, MAPT/tauHist47Tyr,IL-6572 G/C andIL-6RAsp358Alawith the risk of concussion in college athletes.MethodsA 23-centre prospective cohort study of 1056 college athletes with genotyping was completed between August 2003 and December 2012. All athletes completed baseline medical and concussion questionnaires, and post-concussion data were collected for athletes with a documented concussion.ResultsThe study cohort consisted of 1056 athletes of mean±SD age 19.7±1.5 years,89.3% male, 59.4% Caucasian, 35.0% African-American, 5.6% other race. The athletes participated in American football, soccer, basketball, softball, men’s wrestling and club rugby. A total of 133 (12.1% prevalence) concussions occurred during an average surveillance of 3 years per athlete. We observed a significant positive association betweenIL-6RCC (p=0.001) and a negative association betweenAPOE4 (p=0.03) and the risk of concussion. Unadjusted and adjusted logistic regression analysis showed a significant association betweenIL-6RCC and concussion (OR 3.48; 95% CI 1.58 to 7.65; p=0.002) and between the APOE4 allele and concussion (OR 0.61; 95% CI 0.38 to 0.96; p=0.04), which persisted after adjustment for confounders.ConclusionsIL-6RCC was associated with a three times greater concussion risk andAPOE4 with a 40% lower risk.

Millions of concussions occur every year in the United States. The public interest in concussion has increased after a number of high-profile deaths in high school athletes from sports-related head trauma and in some professional athletes from chronic traumatic encephalopathy. One of the most active areas of research in sports medicine during the last decade has been the evaluation and management of concussion. In this second article of a two-part series, we provide an overview of the latest scientific advances in concussion research. This overview includes an update on the pathobiological changes that occur during concussion and the results of biomechanical studies. In addition, to aid the practicing clinician, we review the literature on proven and currently studied concussion risk factors, including a history of concussion, fatigue, and age. Genetic polymorphisms and biomarkers may provide risk-prediction capability, but at present the research remains inconclusive. Diffusion tensor imaging and functional magnetic resonance imaging are promising technologies that reveal more sophisticated data about the impact of concussion on the brain. We review the existing literature on the application of these neuroimaging modalities to sports concussion. An update from the Fourth International Conference on Concussion in Sport, with highlights of new recommendations, and the presentation of the third edition of the Sports Concussion Assessment Tool to evaluate acute concussion, concludes our review.

Approximately 3.8 million sports related TBIs occur per year. Genetic variation may affect both TBI risk and post-TBI clinical outcome. Limited research has focused on genetic risk for concussion among athletes. We describe the design, methods, and baseline characteristics of this prospective cohort study designed to investigate a potential association between genetic polymorphisms of apolipoprotein E gene, APOE promoter G-219T, and Tau gene exon 6 polymorphisms (Ser53 Pro and Hist47Tyr) with: 1) the risk of prospective concussion; 2) concussion severity; and 3) postconcussion neurocognitive recovery.The prospective cohort study included a final population of 2947 college, high school, and professional athletes. Baseline data collection included a concussion/medical history questionnaire, neuropsychological (NP) testing, and genetic sampling for the genetic polymorphisms. Data collection on new concussions experienced utilized post-concussion history/mental status form, Lovell post-concussion symptom score, Standardized Assessment of Concussion (SAC) and/or the Sports Concussion Assessment Tool (SCAT)-1/SCAT-2, and post-concussion NP testing.This paper is focused on discussing the important methodological considerations, organizational challenges and lessons learned in the completion of a multi-center prospective cohort study. A total of 3740 subjects enrolled, with a total of 335 concussions experienced.Of critical importance to the success of a study of this type is to successfully recruit committed institutions with qualified local study personnel, obtain "buy-in" from study sites, and cultivate strong working relationships with study sites. The use of approved incentives may improve study site recruitment, enhance retention, and enhance compliance with study protocols. Future publications will detail the specific findings of this study. Collaborative research is very likely needed given the nature of this study population.

The management of sports concussion and an understanding of its risk factors are major foci in the literature on athletic injury. Although there is known influence of some genetic polymorphisms (GPs), such as APOE and the APOE promoter, on traumatic brain injury (TBI) outcome in non-athletic populations, very little work has focused on the role these GPs may play in sports concussion. We completed a large (n=3274) multi-center prospective cohort study of college athletes to study possible associations between various GPs and prospectively occurring sports concussion. We found no significant relationship between the APOE e4 allele, the APOE G-219T promoter, the tau exon 6 Ser53pro or the tau His47Tyr GPs on prospective concussion. Additional study of other GPs and haplotype combinations is a next logical step in the search for genetic predisposition to sports-related concussion.

SummaryAnalyses of the height variation of 16-year-old members of the British National Child Development Study revealed a number of biological and social variables which associated with stature. After multiple regression analyses only eight variables, namely social class, family size, tenure (owner occupied or one of several types of rented home), crowding status, number of children sleeping in the bed, region of the country, sex of child, and pubic hair rating, remained significant. The total variation explained by these biosocial variables was 37·5%.

OBJECTIVE: To investigate associations of APOE, APOE promoter (G-219T), and tau protein exon 6 polymorphisms (47 and 53) and a history of self-reported concussion in college athletes. DESIGN: Multi-center cross-sectional study. SETTING: Male football and male and female soccer programs at the University of South Carolina, Jacksonville University, Benedict College, and the College of Charleston. PARTICIPANTS: Active 18- to 30-year-old (n = 195) intercollegiate male football players and male and female soccer players during 2001 and 2002. ASSESSMENT OF RISK FACTORS: Written questionnaires and blood or mouthwash samples for DNA for genotyping by RFLP/PCR. MAIN OUTCOME MEASUREMENT: Self-reported history of concussions over the previous 8 years. RESULTS: A statistically significant, nearly 3-fold increase in risk of a history of concussion for those with the APOE promoter G-219T TT genotype relative to the GG genotype (OR, 2.8; 95% CI, 1.1 to 6.9) adjusted for age, sport, school, and years in their primary sport, a finding that was stronger for Cantu grade 2 and 3 concussions. CONCLUSIONS: These results suggest that college athletes with an APOE promoter G-219T TT genotype may be at increased risk for having a history of concussions, especially more severe concussions. Although there was some support for the possibility that the tau 53 polymorphism may be associated with increased risk of prior concussion (OR, 2.1; 95% CI, 0.3 to 14.5), there was no support for an association with APOE genotypes. The results of this cross-sectional study support the need for a prospective study of genetic factors, such as APOE promoter polymorphisms, and the incidence of and sequelae from concussions in college athletes. Language: en

Concussion or mild traumatic brain injury (MTBI) is a major sports medicine issue in the current medical literature and in the popular media. Well-publicized cases of careers ended by the results of multiple concussions as well as the potential for long-term neurocognitive deficits due to multiple concussions have raised concerns. This review will discuss the epidemiology, anatomy, and physiology of concussion, as well as the clinical evaluation, grading scales, risk of chronic traumatic brain injury, and research on genetic risk factors for concussion. The main focus of this article is to review the clinical evaluation and management of concussion, including return to play criteria and use of neuropsychological testing for the practicing physician. An estimated 300,000 sports-related traumatic brain injuries of mild to moderate severity occur in the United States each year.' Football, ice hockey, soccer, and rugby are sports with the highest concussion prevalence. Some studies show that up to 15% of people diagnosed with MTBI experience persistent disabling symptoms.^"''

Human growth hormone (GH) has a number of accepted medical uses, but has quickly become a popular ergogenic aid among athletes. The issue of performance-enhancing substances such as anabolic steroids and GH has drawn the attention of athletes, their parents, and politicians. On almost a daily basis, headlines about the status of doping in professional, international, and amateur sports seem to be more pervasive. The supraphysiologic effects of GH lead to lipolysis, with increased muscle volume. Due to the ethical limitations of studying the use of high doses of GH in isolation or combined with anabolic steroids, the scientific literature has not produced compelling results on its efficacy. GH has potential as an anti-aging drug and does lead to some improved athletic performance in isolated studies. Despite the lack of compelling data, GH seems to have developed a reputation among athletes for enhancing performance. The detection of illegal doping with GH has been the focus of a concerted international effort by the International Olympic Committee. A number of promising detection techniques may allow the detection of illicit GH use. This review on GH as an ergogenic aid includes a discussion of the basic physiology of GH and its actions, the accepted medical indications for its use, the results of scientific studies that assess whether it improves exercise performance or work capacity, and the scientific techniques under development to detect ergogenics with strong abuse potential.

Objective To investigate associations of APOE and Tau gene polymorphisms with sports-related acute concussions and baseline to post-concussion neuropsychological test score changes. Design Multi-center prospective cohort study. Setting Scholarship athletes at 21 universities and 4 high schools Participants: 3218 athletes playing football (70%) or soccer (23%). Assessment of Risk Factors APOE , APOE G-219T promoter (APOEProm), Tau exon 6 Ser53Pro (TauSer), and Tau exon 6 Hist47Tyr (TauHis) genetic polymorphisms. Main Outcome Measurements (1) Acute concussions and (2) differences between baseline and 24–72 h post-concussion Headminder Neuropsychological Test Scores of Simple and Complex Reaction Time (SRT and CRT, respectively) and Processing Speed. Results There were a total of 131 athletes with incident concussions and genetic data and neuropsychological test scores. There were no statistically significant differences in frequencies of acute concussions according to genotypes by χ 2 test. By t-test, the mean baseline to post-concussion neuropsychological changes were statistically significantly greater for CRT and SRT in those with the TauSer ‘TT’ genotype and for CRT in those with the APOEProm ‘TT’ genotype, and borderline significantly greater in those with the TauSer ‘TT’ genotype (p=0.09). Conclusions The statistically significantly worse mean baseline to post-concussion neuropsychological test scores in those with the APOEProm and TauSer polymorphisms suggests a possible genetic influence on post-concussion neurocognitive recovery. These preliminary findings provide no evidence for associations of the four APOE and Tau gene polymorphisms investigated with acute concussions, although the small sample size and lack of control for confounders are limitations. Acknowledgements Grant funding was provided through the NOCSAE (National Operating Committee for Safety Athletic Equipment) and the American Medical Society for Sports Medicine (AMSSM) Foundations. The opinions expressed in this abstract are not those of NOCSAE or AMSSM. Competing interests None.

Letting (T(t): t ⩾ 0) be a strongly continuous semigroup of contraction operators on L1(X,M,λ) we consider the question of the almost-everywhere convergence of (1α) ∝0α T(t)ƒ dt as α → 0 + (the local ergodic theorem). The limit is known to exist in the case where the semigroup is positive. In this paper we consider the question for general semigroups which may contain nonpositive elements. We show that a maximal ergodic inequality is equivalent to the local ergodic theorem. We also present some extensions to the local ergodic theorem. All the results of this paper also hold for N-parameter semigroups.

The main purpose of this paper is to prove the following local ergodic theorem. If {T(t1,…,tN): ti ≥ 0, i=1,…,N} is an N-parameter strongly continuous semigroup of positive contraction operators on L1(Θ,F,μ), then for all f є L1(Θ) \(M\left( \varepsilon \right)f = \frac{1}{{_\varepsilon N}}\int_o^\varepsilon \ldots \int_o^\varepsilon {T\left( {t_1 , \ldots ,t_N } \right)f dt_1 } \ldots dt_N\) converges almost everywhere as e + 0 + . The theorem will also be proved for semigroups of non-positive L1 contractions which are also L∞ contracting. Examples are given to show that the maximal ergodic lemmas which are used to prove the one parameter case of the above results do not extend to the N-parameter case. The N-parameter case is proved by successive reduction of the number of parameters.