Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Neuromuscular Fatigue and Muscle Damage After a Women's Rugby Sevens Tournament

Purpose:To examine relationships between on-field game movement patterns and changes in markers of neuromuscular fatigue and muscle damage during a 2-d women’s rugby sevens tournament.Methods:Female national (mean ± SD n = 12, 22.3 ± 2.5 y, 1.67 ± 0.04 m, 65.8 ± 4.6 kg) and state (n = 10, 24.4 ± 4.3 y, 1.67 ± 0.03 m, 66.1 ± 7.9 kg) representative players completed baseline testing for lower-body neuromuscular function (countermovement-jump [CMJ] test), muscle damage (capillary creatine kinase [CK]), perceived soreness, and perceived recovery. Testing was repeated after games on days 1 and 2 of the tournament. GPS (5-Hz) data were collected throughout the tournament (4−6 games/player).Results:National players were involved in greater on-field movements for total time, distance, high-speed running (&gt;5 m/s), and impacts &gt;10 g (effect size [ES] = 0.55−0.97) and displayed a smaller decrement in performance from day 1 to day 2. Despite this, state players had a much greater 4-fold increase (ΔCK = 737 U/L) in CK compared with the 2-fold increase (ΔCK = 502 U/L) in national players (ES = 0.73). Both groups had similar perceived soreness and recovery while CMJ performance was unchanged. High-speed running and impacts &gt;10 g were largely correlated (r = .66−.91) with ΔCK for both groups.Conclusion:A 2-day women’s rugby sevens tournament elicits substantial muscle damage; however, there was little change in lower-body neuromuscular function. Modest increases in CK can largely be attributed to high-speed running and impacts &gt;10 g that players typically endure.</jats:sec

High-intensity cycle interval training improves cycling and running performance in triathletes

Effective cycle training for triathlon is a challenge for coaches. We compared the effects of two variants of cycle high-intensity interval training (HIT) on triathlon-specific cycling and running. Fourteen moderately-trained male triathletes (_VO2peak 58.7 ± 8.1 mL kg − 1 min − 1; mean ± SD) completed on separate occasions a maximal incremental test (_VO2peak and maximal aerobic power), 16 × 20 s cycle sprints and a 1-h triathlon-specific cycle followed immediately by a 5 km run time trial. Participants were then pair-matched and assigned randomly to either a long high-intensity interval training (LONG)(6 – 8 × 5 min efforts) or short high-intensity interval training (SHORT) (9 – 11 × 10, 20 and 40 s efforts) HIT cycle training intervention. Six training sessions were completed over 3 weeks before participants repeated the baseline testing. Both groups had an ~ 7% increase in _VO2peak (SHORT 7.3%, ± 4.6%; mean, ± 90% confidence limits; LONG 7.5%, ± 1.7%). There was a moderate improvement in mean power for both the SHORT (10.3%, ± 4.4%) and LONG (10.7%, ± 6.8%) groups during the last eight 20-s sprints. There was a small to moderate decrease in heart rate, blood lactate and perceived exertion in both groups during the 1-h triathlon-specific cycling but only the LONG group had a substantial decrease in the subsequent 5-km run time (64, ± 59 s). Moderately-trained triathletes should use both short and long high-intensity intervals to improve cycling physiology and performance. Longer 5-min intervals on the bike are more likely to benefit 5 km running performance

Physiological, anthropometric, and performance characteristics of rugby sevens players

Although the characteristics of 15-a-side rugby union players have been well defined, there is little information on rugby sevens players.\ud \ud PURPOSE:\ud \ud The authors profiled the anthropometric, physiological, and performance qualities of elite-level rugby sevens players and quantified relationships between these characteristics.\ud \ud METHODS:\ud \ud Eighteen male international rugby sevens players undertook anthropometric (body mass, height, sum of 7 skinfolds, lean-mass index), acceleration and speed (40-m sprint), muscle-power (vertical jump), repeated-sprint-ability (6 × 30-m sprint), and endurance (Yo-Yo Intermittent Recovery test and treadmill VO2max) testing. Associations between measurements were assessed by correlation analysis.\ud \ud RESULTS:\ud \ud Rugby sevens players had anthropometric characteristics (body mass 89.7 ± 7.6 kg, height 1.83 ± 0.06 m, sum of 7 skinfolds 52.2 ± 11.5 mm; mean ± SD) similar to those of backs in international 15-player rugby union. Acceleration and speed (40-m sprint 5.11 ± 0.15 s), muscle-power (vertical jump 66 ± 7 cm), and endurance (VO2max 53.8 ± 3.4 mL · kg-1 · min-1) qualities were similar to, or better than, those of professional 15-a-side players. Coefficients of variation ranged from 2.5% to 22%. Relative VO2max was largely correlated with Yo-Yo distance (r = .60, .21-.82; 90% confidence interval) and moderately correlated with 40-m sprint time (r = -.46, -.75 to -.02) and repeated-sprint ability (r = -.38, -.72 to .09).\ud \ud CONCLUSIONS:\ud \ud International rugby sevens players require highly developed speed, power, and endurance to tolerate the demands of competition. The small between-athletes variability of characteristics in rugby sevens players highlights the need for relatively uniform physical and performance standards in contrast with 15-a-side players

Association between Physical Functionality and Falls Risk in Community-Living Older Adults

Ageing-related declines in physiological attributes, such as muscle strength, can bring with them an increased risk of falls and subsequently greater risk of losing independence. These declines have substantial impact on an individual&apos;s functional ability. However, the precise relationship between falls risk and physical functionality has not been evaluated. The aims of this study were to determine the association between falls risk and physical functionality using objective measures and to create an appropriate model to explain variance in falls risk. Thirty-two independently living adults aged 65-92 years completed the FallScreen, the Continuous-Scale Physical Functional Performance 10 (CS-PFP10) tests, and the 12-Item Short-Form Health Survey (SF-12). The relationships between falls risk, physical functionality, and age were investigated using correlational and multiple hierarchical regression analyses. Overall, total physical functionality accounted for 24% of variance in an individual&apos;s falls risk while age explained a further 13%. The oldest-old age group had significantly greater falls risk and significantly lower physical functional performance. Mean scores for all measures showed that there were substantial (but not significant) differences between males and females. While increasing age is the strongest single predictor of increasing falls risk, poorer physical functionality was strongly, independently related to greater falls risk

Diagnostic differentiation by NIH Toolbox- Cognition (iPAD) for Alzheimer- s disease, mild cognitive impairment (MCI), and healthy control participants

BackgroundAge- associated impairment among older adults is a significant public health concern. The NIH Toolbox for Assessment of Neurological and Behavioral Function® (NIHTB) was developed for use in studies for which standardized, computer- based measurement of cognitive, motor, sensory, and behavioral processes is of importance. The NIH Toolbox- Cognition battery measures both crystallized and fluid cognitive functions. The goal of this study was to compare performance of the newly available tablet- version of the Cognition battery across healthy and impaired older adults and to analyze if race and gender effects would be evident even when using NIHTB fully- adjusted T- scores.MethodA total of 104 individuals (28 men, 56 women; 45% African American) completed the NIH Toolbox- Cognition as part of a National Alzheimer- s Disease Coordinating Center (NACC) longitudinal study of memory and aging through the Michigan Alzheimer- s Disease Research Center (Michigan ADRC). All participants received the Unified Data Set (UDS) and consensus diagnosis of normal cognition (NL), amnestic mild cognitive impairment (aMCI), or Alzheimer- s dementia (AD). Univariate analyses of variance with post- hoc comparisons were used to compare fully adjusted (age, gender, race/ethnicity, education) Toolbox T- Score performance across the groups.ResultsUnivariate ANOVAs revealed significant findings for the Total and Fluid composites (both pAD. Though NL and aMCI groups performed similarly, both groups outperformed AD on Dimensional Card Sort, Flanker, and Pattern Comparison Fluid subtests. NL>aMCI>AD on List Sorting Working Memory and Picture Sequence Memory. Main effects for race or gender were not seen for comparisons of NL to aMCI, but some group sizes were too small for adequate testing in the AD participants.ConclusionsAs expected, NL, aMCI, and AD demonstrated significant performance differences on NIH Toolbox- Cognition composite and scale scores. As expected, Crystallized tasks were least effective, traditionally representing cognitive areas least sensitive to neurologic dysfunction. Fluid tasks were noticeably more effective, with the working memory and learning measures showing a significant tiered difference, with NL highest and AD lowest. The fully adjusted scores were successful in accounting for demographic variables.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163884/1/alz046086.pd

Intravenous iron supplementation in distance runners with low or suboptimal ferritin

Purpose: Iron deficiency is prevalent in distance runners and may impair endurance performance. The current practice of oral supplementation is slow and often not well tolerated. The aim of this study was to assess the efficacy of intravenous (IV) iron supplementation (ferric carboxymaltose) compared with oral supplementation (ferrous sulfate) on iron status, hemoglobin mass (Hbmass), and physiological indices of running performance in distance runners. Methods: Twenty-seven highly trained distance runners with low (LOW) (ferritin < 35 [mu]g[middle dot]L-1 and transferrin saturation < 20%, or ferritin < 15 [mu]g[middle dot]L-1) or suboptimal (SUB) iron status (ferritin < 65 [mu]g[middle dot]L-1) were supplemented with either IV iron (Ferinject(R)) or oral (ORAL) supplements (Ferrogradumet) for 6 wk. Iron status and Hbmass were assessed before supplementation and at 1, 2, 4, 6, and 8 wk in the four groups (IV LOW, IV SUB, ORAL LOW, and ORAL SUB). In addition, athletes completed a treadmill running test for running economy, lactate threshold, and V[spacing dot above]O2max before and after supplementation. Results: Both forms of supplementation substantially increased ferritin levels in all four groups. IV supplementation resulted in higher ferritin in both IV groups compared with both ORAL groups from week 1 onward. Hemoglobin concentration did not change substantially in any group. Hbmass increased in IV LOW (mean = +4.9%, 90% confidence interval [CI] = 1.1%-8.9%) and was accompanied by an increase in V[spacing dot above]O2max (mean = +3.3%, 90% CI = 0.4%-6.3%) and run time to exhaustion (mean = +9.3%, 90% CI = 0.9%-18.3%. Conclusions: IV supplementation can effectively increase iron stores in iron-deficient runners within 6 wk and, if Hbmass is compromised, may enhance endurance capacity by facilitating erythropoiesis. Hbmass appears a more sensitive tool for measuring changes in whole body hemoglobin than hemoglobin concentration and may be useful in the diagnosis and follow-up for iron deficiency