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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

Trends in Moderate-to-Vigorous Physical Activity among Veterans: Findings from the National Health Interview Survey 2011-2020

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Applying theories of health behaviour and change to hearing health research: time for a new approach

Objective: In recent years, there has been an increase in the application of behavioural models, such as social cognition models, to the promotion of hearing health. Despite this, there exists a well-developed body of literature that suggests such models may fail to consistently explain reliable amounts of variability in human behaviours. Design: This paper provides a summary of this research across selected models of health-related behaviour, outlining the current state of the evidence. Results: Recent work in the field of behaviour change is presented together with commentary on the design and reporting of behaviour change interventions. Conclusions: We propose that attempts to use unreliable models to explain and predict hearing health behaviours should now be replaced by work which integrates the latest in behaviour change science, such as the Behaviour Change Wheel and Theoretical Domains Framework

Scaling up prevention and treatment towards the elimination of hepatitis C: a global mathematical model

Background The revolution in hepatitis C virus (HCV) treatment through the development of direct-acting antivirals (DAAs) has generated international interest in the global elimination of the disease as a public health threat. In 2017, this led WHO to establish elimination targets for 2030. We evaluated the impact of public health interventions on the global HCV epidemic and investigated whether WHO's elimination targets could be met. Methods We developed a dynamic transmission model of the global HCV epidemic, calibrated to 190 countries, which incorporates data on demography, people who inject drugs (PWID), current coverage of treatment and prevention programmes, natural history of the disease, HCV prevalence, and HCV-attributable mortality. We estimated the worldwide impact of scaling up interventions that reduce risk of transmission, improve access to treatment, and increase screening for HCV infection by considering six scenarios: no change made to existing levels of diagnosis or treatment; sequentially adding the following interventions: blood safety and infection control, PWID harm reduction, offering of DAAs at diagnosis, and outreach screening to increase the number diagnosed; and a scenario in which DAAs are not introduced (ie, treatment is only with pegylated interferon and oral ribavirin) to investigate the effect of DAA use. We explored the effect of varying the coverage or impact of these interventions in sensitivity analyses and also assessed the impact on the global epidemic of removing certain key countries from the package of interventions. Findings By 2030, interventions that reduce risk of transmission in the non-PWID population by 80% and increase coverage of harm reduction services to 40% of PWID could avert 14·1 million (95% credible interval 13·0–15·2) new infections. Offering DAAs at time of diagnosis in all countries could prevent 640 000 deaths (620 000–670 000) from cirrhosis and liver cancer. A comprehensive package of prevention, screening, and treatment interventions could avert 15·1 million (13·8–16·1) new infections and 1·5 million (1·4–1·6) cirrhosis and liver cancer deaths, corresponding to an 81% (78–82) reduction in incidence and a 61% (60–62) reduction in mortality compared with 2015 baseline. This reaches the WHO HCV incidence reduction target of 80% but is just short of the mortality reduction target of 65%, which could be reached by 2032. Reducing global burden depends upon success of prevention interventions, implemention of outreach screening, and progress made in key high-burden countries including China, India, and Pakistan. Interpretation Further improvements in blood safety and infection control, expansion or creation of PWID harm reduction services, and extensive screening for HCV with concomitant treatment for all are necessary to reduce the burden of HCV. These findings should inform the ongoing global action to eliminate the HCV epidemic

Gram - positive and gram - negative subcellular localization using rotation forest and physicochemical-based features

The functioning of a protein relies on its location in the cell. Therefore, predicting protein subcellular localization is an important step towards protein function prediction. Recent studies have shown that relying on Gene Ontology (GO) for feature extraction can improve the prediction performance. However, for newly sequenced proteins, the GO is not available. Therefore, for these cases, the prediction performance of GO based methods degrade significantly. Results: In this study, we develop a method to effectively employ physicochemical and evolutionary-based information in the protein sequence. To do this, we propose segmentation based feature extraction method to explore potential discriminatory information based on physicochemical properties of the amino acids to tackle Gram-positive and Gram-negative subcellular localization. We explore our proposed feature extraction techniques using 10 attributes that have been experimentally selected among a wide range of physicochemical attributes. Finally by applying the Rotation Forest classification technique to our extracted features, we enhance Gram-positive and Gram-negative subcellular localization accuracies up to 3.4% better than previous studies which used GO for feature extraction. Conclusion: By proposing segmentation based feature extraction method to explore potential discriminatory information based on physicochemical properties of the amino acids as well as using Rotation Forest classification technique, we are able to enhance the Gram-positive and Gram-negative subcellular localization prediction accuracies, significantly

Association between coffee, caffeine and gut biodiversity: A United States - Veteran Microbiome Project Sub - Study

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