Association between MAPT polymorphism but not APOE promoter and elite rugby athlete status

INTRODUCTION: Incidence and outcomes of concussions have been hypothesised to be genetically influenced. The APOE Promoter G219T (rs405509) polymorphism has been associated with differential promoter activity and unfavourable outcomes after traumatic brain injury. The TT genotype is associated with a 3-fold greater risk of multiple concussions. The TT genotype of MAPT (rs10445337) has also been associated with poorer outcomes after concussion. Rugby has one of the highest incidences of concussion in sport, so it was hypothesised that APOE Promoter TT and MAPT TT genotypes would be less prevalent in elite rugby athletes because those genotypes, previously associated with increased risk, would be less compatible with achieving elite athlete status. METHODS: Participants were from the RugbyGene project, comprising elite Caucasian male rugby athletes (n = 528; mean (standard deviation) height 1.85 (0.07) m, mass 101 (14) kg, age 29 (7) yr), including 420 rugby union (RU) athletes that for some analyses were divided into forwards and backs and 108 rugby league (RL) athletes. Non-athletes were 592 Caucasian men and women (57% male, height 1.72 (0.10) m, mass 74 (14) kg, age 31 (7) yr). PCR of genomic DNA was used to determine genotypes using TaqMan probes, then groups were compared using χ2 and odds ratio (OR) statistics. RESULTS: All genotype data were in Hardy-Weinberg equilibrium. For MAPT (rs10445337), the risk genotype (TT) was underrepresented in rugby athletes (60%) compared to non-athletes (66%), CT more common in rugby athletes (34%) than non-athletes (29%) and little difference in CC genotype frequencies (χ2 = 7.092, P = 0.029; TT genotype frequency OR = 0.80, 95% confidence intervals (CI) = 0.62-1.02). There were no differences in MAPT (rs10445337) genotype frequencies between RU forwards and backs. For APOE Promoter G219T (rs405509), there were no differences in genotype frequencies between all athletes (RU and RL) and non-athletes (27% TT genotype in players and non-athletes), nor between RU forwards and backs. CONCLUSION: The MAPT (rs10445337) TT genotype is 6% less common in elite rugby athletes than non-athletes. Therefore, carrying at least one rs10445337 C allele appears to increase the probability of sustained career success in the high-risk concussion environment of elite rugby, perhaps via a greater ability to recover from concussions.Peer reviewe

Association of MMP3 but not TIMP2 gene variants with elite rugby player status and rugby code

Introduction: Achilles tendon pathology and anterior cruciate ligament rupture are multifactorial conditions for which genetic risk factors have been identified. Single nucleotide polymorphisms (SNPs) within the MMP3 (rs591058, rs679620, rs650108) and TIMP2 (rs4789932) genes have previously been associated with tendon and ligament pathologies. Although not entirely clear, prior literature indicates the risk alleles for Achilles tendon pathology as T (rs591058), G (rs679620) and A (rs650108) for MMP3. However, prior evidence regarding TIMP2 is equivocal. MMP3 is considered an essential regulator of matrix degradation and remodelling within diseased and normal musculoskeletal soft tissues. TIMP2 maintains homeostasis in the extracellular matrix in part by inhibiting MMP function. Given the high incidence and severity of tendon and ligament injuries in elite rugby athletes, we hypothesised that the aforementioned SNPs would be associated with career success. Methods: Participants from the RugbyGene project were elite Caucasian male rugby athletes (n = 566; mean (standard deviation) height 1.85 (0.07) m, mass 101 (14) kg, age 29 (7) yr), including 420 rugby union (RU) athletes that for some analyses were divided into forwards and backs and 120 rugby league (RL) athletes. Non-athletes were 589 Caucasian men and women (n = 589, 57% male, height 1.72 (0.10) m, mass 74 (14) kg, age 31 (7) yr). PCR of genomic DNA was used to determine genotypes using TaqMan probes, then groups were compared using Χ2 and odds ratio (OR) statistics. Results: As hypothesized, the MMP3 rs591058 risk genotype (TT) was less frequent in rugby athletes (28%) compared to non-athletes (33%) (Χ2 = 7.265, P = 0.026; OR = 1.18, 95% confidence intervals (CI) = 0.86-1.63). No differences were found for MMP3 rs679620, rs650108 or TIMP2 rs4789932 between rugby athletes and non-athletes. When RL athletes were compared to non-athletes, the risk genotype (TT) of MMP3 rs591058 was underrepresented in RL athletes (19%) compared to non-athletes (33%). The MMP3 rs679620 ‘protective’ allele (C) was more frequent in RL athletes (55%) compared to non-athletes (48%) (OR = 1.3, 95% CI = 0.98-1.74). However, for MMP3 rs650108 the ‘risk’ allele (A) was overrepresented in RL athletes (32%) compared to non-athletes (26%). There were no genotype differences for any gene variant between RU athletes and non-athletes. The ‘risk’ allele (T) of the MMP3 rs679629 polymorphism and the ‘protective’ allele (G) of the MMP3 rs650108 polymorphism were less common in RL (45%, 68%, respectively) than RU athletes (54%, 76%, respectively). Conclusion: We provide evidence for elite rugby athletes possessing a protective genetic profile regarding tendon and ligament injury risk. Notably, a less frequent rs591058 TT genotype in athletes suggests a lower risk of injury could therefore enhance career success in rugby. Furthermore, RL players appear to have differing genetic characteristics compared to their RU counterparts, which might reflect some differences in physiological demands between codes.Peer reviewedFinal Published versio

Evaluation of school absenteeism data for early outbreak detection, New York City

BACKGROUND: School absenteeism data may have utility as an early indicator of disease outbreaks, however their value should be critically examined. This paper describes an evaluation of the utility of school absenteeism data for early outbreak detection in New York City (NYC). METHODS: To assess citywide temporal trends in absenteeism, we downloaded three years (2001–02, 2002–03, 2003–04) of daily school attendance data from the NYC Department of Education (DOE) website. We applied the CuSum method to identify aberrations in the adjusted daily percent absent. A spatial scan statistic was used to assess geographic clustering in absenteeism for the 2001–02 academic year. RESULTS: Moderate increases in absenteeism were observed among children during peak influenza season. Spatial analysis detected 790 significant clusters of absenteeism among elementary school children (p < 0.01), two of which occurred during a previously reported outbreak. CONCLUSION: Monitoring school absenteeism may be moderately useful for detecting large citywide epidemics, however, school-level data were noisy and we were unable to demonstrate any practical value in using cluster analysis to detect localized outbreaks. Based on these results, we will not implement prospective monitoring of school absenteeism data, but are evaluating the utility of more specific school-based data for outbreak detection

Denitrification and inference of nitrogen sources in the karstic Floridan Aquifer

Aquifer denitrification is among the most poorly constrained fluxes in global and regional nitrogen budgets. The few direct measurements of denitrification in groundwaters provide limited information about its spatial and temporal variability, particularly at the scale of whole aquifers. Uncertainty in estimates of denitrification may also lead to underestimates of its effect on isotopic signatures of inorganic N, and thereby confound the inference of N source from these data. In this study, our objectives are to quantify the magnitude and variability of denitrification in the Upper Floridan Aquifer (UFA) and evaluate its effect on N isotopic signatures at the regional scale. Using dual noble gas tracers (Ne, Ar) to generate physical predictions of N&lt;sub&gt;2&lt;/sub&gt; gas concentrations for 112 observations from 61 UFA springs, we show that excess (i.e. denitrification-derived) N&lt;sub&gt;2&lt;/sub&gt; is highly variable in space and inversely correlated with dissolved oxygen (O&lt;sub&gt;2&lt;/sub&gt;). Negative relationships between O&lt;sub&gt;2&lt;/sub&gt; and &amp;delta;&lt;sup&gt;15&lt;/sup&gt;N&lt;sub&gt;NO3&lt;/sub&gt; across a larger dataset of 113 springs, well-constrained isotopic fractionation coefficients, and strong &lt;sup&gt;15&lt;/sup&gt;N:&lt;sup&gt;18&lt;/sup&gt;O covariation further support inferences of denitrification in this uniquely organic-matter-poor system. Despite relatively low average rates, denitrification accounted for 32 % of estimated aquifer N inputs across all sampled UFA springs. Back-calculations of source &amp;delta;&lt;sup&gt;15&lt;/sup&gt;N&lt;sub&gt;NO3&lt;/sub&gt; based on denitrification progression suggest that isotopically-enriched nitrate (NO&lt;sub&gt;3&lt;/sub&gt;&lt;sup&gt;&amp;ndash;&lt;/sup&gt;) in many springs of the UFA reflects groundwater denitrification rather than urban- or animal-derived inputs

A Model for the Diffuse γ-Ray Spectrum

A model is proposed to describe the observed shelf in the cosmic diffuse radiation spectrum just above 1 MeV. This model is based on induced positronium annihilation, which at incident photon energy 2 mc^2 gives rise to enhancement of the radiative field. It is proposed that this amplification may occur in double radio sources or other accreting objects. Recent observation of γ-ray line emission from the double radio sources SS 433 at 1.2 and 1.5 MeV is in good agreement with the proposed model

Lunar multispectral mosaics from Galileo's second Earth-Moon flyby

Galileo's Solid-State Imaging (SSI) experiment acquired about 800 images of the Moon from the second Earth-Moon flyby (EM2) in December of 1992. Ten major sequences were acquired; each consists of mosaics of the entire or nearly entire visible and illuminated surface from each viewing geometry in at least six spectral filters (effective wavelengths for the Moon of 420, 564, 660, 756, 890, and 990 nm). The geometries of LUNMOS numbers 3, 4, 5, and 6 were designed to provide stereo data at the best possible resolutions. The purpose of this abstract is to describe the sequences, calibration, processing, and mosaicking, and to present a set of color products in a poster session

An Investigation into Genetic Associations with Musculoskeletal Soft Tissue Injuries in Elite Rugby – Preliminary Findings

Peer reviewe

The effect of signal acquisition and processing choices on ApEn values: Towards a “gold standard” for distinguishing effort levels from isometric force records

Approximate Entropy (ApEn) is frequently used to identify changes in the complexity of isometric force records with ageing and disease. Different signal acquisition and processing parameters have been used, making comparison or confirmation of results difficult. This study determined the effect of sampling and parameter choices by examining changes in ApEn values across a range of submaximal isometric contractions of the First Dorsal Interosseus. Reducing the sample rate by decimation changed both the value and pattern of ApEn values dramatically. The pattern of ApEn values across the range of effort levels was not sensitive to the filter cut-off frequency, or the criterion used to extract the section of data for analysis. The complexity increased with increasing effort levels using a fixed ‘r’ value (which accounts for measurement noise) but decreased with increasing effort level when ‘r’ was set to 0.1 of the standard deviation of force. It is recommended isometric force records are sampled at frequencies >200 Hz, template length (‘m’) is set to 2, and 'r' set to measurement system noise or 0.1 SD depending on physiological process to be distinguished. It is demonstrated that changes in ApEn across effort levels are related to changes in force gradation strategy

Effect of Beta-Adrenergic Blockade on Coronary Blood Flow during Isometric Exercise in Older Adults

Ross A., Gao Z., Heffernan M., Leuenberger U., Sinoway L., Muller M. Penn State Hershey Heart and Vascular Institute, Pennsylvania State University College of Medicine, Hershey, PA The rise in heart rate (HR) and cardiac contractility during exercise is due to activation of myocardial b-adrenergic receptors. b-receptors are also located on coronary blood vessels and are thought to participate in exercise hyperemia, thereby helping to preserve the balance between myocardial oxygen supply and demand. However, experimental data in human subjects are lacking. Purpose: We hypothesized that intravenous b-adrenergic blockade would attenuate the reflex tachycardia and coronary hyperemia in response to isometric handgrip (i.e., a stimulus known to increase both cardiac metabolism and coronary blood flow). Methods: Six men (66 ± 2 yrs) performed isometric handgrip exercise at 40% of maximal voluntary contraction for 2 minutes after receiving intravenous propranolol; control trials occurred on separate days. HR and blood pressure were monitored continuously and rate-pressure product (RPP) was calculated as an index of myocardial oxygen demand. Coronary blood flow velocity (CBFV) was measured by transthoracic Doppler echocardiography (left anterior descending coronary artery) and coronary vascular resistance (CVR) was calculated. The ratio of RPP/CVR was used as an index of myocardial oxygen supply. Physiological parameters were statistically compared at baseline and in response to exercise between conditions. Results: Refer to Table. Conclusion: The novel finding of this study is that under resting conditions propranolol raises coronary resistance (impaired oxygen supply) despite also lowering cardiac metabolism (reduced oxygen demand). These data support the concept that coronary b-adrenergic receptors contribute to myocardial blood flow regulation both at rest and during exercise in humans. Supported by NIH P01 HL096570 and UL1 TR00012