TRITIUM, HYDROGEN AND OXYGEN ISOTOPE COMPOSITIONS IN MONTHLY PRECIPITATION SAMPLES COLLECTED AT TOKI, JAPAN

Monthly precipitation samples have been collected at Toki, Japan, from November 2013 to March 2017. In this report, selected data were analysed to identify the regional hydrogen and oxygen isotope compositions. Tritium (3H) concentration in the precipitation ranged from 0.10 to 0.61 Bq L−1 and higher 3H concentrations were observed in spring rather than in other seasons. This range was similar to values reported in Chiba City, Japan. 3H concentration and the ratio d-excess, and δD values were roughly clustered according to each separate season. These regional hydrogen and oxygen isotope compositions will be used for environmental assessments of effects of the deuterium plasma experiments of the large fusion test device

Systematic literature review of determinants of sedentary behaviour in older adults:a DEDIPAC study

BACKGROUND: Older adults are the most sedentary segment of society and high sedentary time is associated with poor health and wellbeing outcomes in this population. Identifying determinants of sedentary behaviour is a necessary step to develop interventions to reduce sedentary time. METHODS: A systematic literature review was conducted to identify factors associated with sedentary behaviour in older adults. Pubmed, Embase, CINAHL, PsycINFO and Web of Science were searched for articles published between 2000 and May 2014. The search strategy was based on four key elements: (a) sedentary behaviour and its synonyms; (b) determinants and its synonyms (e.g. correlates, factors); (c) types of sedentary behaviour (e.g. TV viewing, sitting, gaming) and (d) types of determinants (e.g. environmental, behavioural). Articles were included in the review if specific information about sedentary behaviour in older adults was reported. Studies on samples identified by disease were excluded. Study quality was rated by means of QUALSYST. The full review protocol is available from PROSPERO (PROSPERO 2014: CRD42014009823). The analysis was guided by the socio-ecological model framework. RESULTS: Twenty-two original studies were identified out of 4472 returned by the systematic search. These included 19 cross-sectional, 2 longitudinal and 1 qualitative studies, all published after 2011. Half of the studies were European. The study quality was generally high with a median of 82 % (IQR 69-96 %) using Qualsyst tool. Personal factors were the most frequently investigated with consistent positive association for age, negative for retirement, obesity and health status. Only four studies considered environmental determinants suggesting possible association with mode of transport, type of housing, cultural opportunities and neighbourhood safety and availability of places to rest. Only two studies investigated mediating factors. Very limited information was available on contexts and sub-domains of sedentary behaviours. CONCLUSION: Few studies have investigated determinants of sedentary behaviour in older adults and these have to date mostly focussed on personal factors, and qualitative studies were mostly lacking. More longitudinal studies are needed as well as inclusion of a broader range of personal and contextual potential determinants towards a systems-based approach, and future studies should be more informed by qualitative work

Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis

Objective To examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality. Design Systematic review and harmonised meta-analysis. Data sources PubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018. Eligibility criteria Prospective cohort studies assessing physical activity and sedentary time by accelerometry and associations with all cause mortality and reported effect estimates as hazard ratios, odds ratios, or relative risks with 95% confidence intervals. Data extraction and analysis Guidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened the titles and abstracts. One author performed a full text review and another extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Data on physical activity were categorised by quarters at study level, and study specific associations with all cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were summarised using random effects meta-analysis. Main outcome measure All cause mortality. Results 39 studies were retrieved for full text review; 10 were eligible for inclusion, three were excluded owing to harmonisation challenges (eg, wrist placement of the accelerometer), and one study did not participate. Two additional studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8% women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9%) deaths were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality, with a non-linear dose-response. Hazards ratios for mortality were 1.00 (referent) in the first quarter (least active), 0.48 (95% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to 0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most active). Corresponding hazards ratios for light physical activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00 (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63 (1.94 to 3.56). Conclusion Higher levels of total physical activity, at any intensity, and less time spent sedentary, are associated with substantially reduced risk for premature mortality, with evidence of a non-linear dose-response pattern in middle aged and older adults. Systematic review registration PROSPERO CRD42018091808

Objectively measured physical activity and sedentary behaviour and ankle brachial index: Cross-sectional and longitudinal associations in older men

AbstractBackgroundAssociations between bouts of physical activity (PA), sedentary behaviour (SB) and cardiovascular disease, and their mutual independence are not well defined. A low ankle brachial index (ABI ≤0.9) indicates peripheral arterial disease (PAD) and is predictive of cardiovascular events and functional impairment. We investigated the independence of PA and SB and the importance of bout duration in relation to ABI using objective measures.Methods945 men from the British Regional Heart Study, mean age 78.4 y, had concurrent measurements of ABI (Vicorder) and physical activity (Actigraph GT3X accelerometer); 427 men also had accelerometer measurements one year previously and contributed data to longitudinal analyses.Results and conclusionIn cross-sectional analyses, after adjusting for covariates each extra 10 min of moderate and vigorous PA per day was associated with an OR of 0.81 (95% CI 0.72, 0.91) for a low ABI, a stronger association than for light PA (OR 0.85, 95% CI 0.75, 0.98). Each extra 30 min of SB was associated with an OR of 1.19 (95% CI 1.07, 1.33) for a low ABI. Associations between moderate and vigorous PA and ABI persisted after adjustment for light PA or SB. Bout lengths for PA and SB were not associated with a low ABI. One year changes in PA or SB were not associated with low ABI.All physical activity and lower levels of SB, regardless of bout duration were inversely associated with ABI; more intense PA showed a stronger association. No associations between changes in PA and ABI were observed, but power may have been limited

Objectively measured physical activity, sedentary time and subclinical vascular disease: Cross-sectional study in older British men.

Low physical activity (PA) and high levels of sedentary time (ST) are associated with higher cardiovascular disease (CVD) risk among older people. However, their independent contribution and importance of duration of PA and ST bouts remain unclear. We investigated associations between objectively measured PA, ST and non-invasive vascular measures, markers of CVD risk. Cross-sectional study of 1216 men from the British Regional Heart Study, mean age 78.5years, measured in 2010-2012. Carotid intima thickness (CIMT), distensibility coefficient (DC) and plaque presence were measured using ultrasound; pulse wave velocity (cfPWV) and augmentation index (AIx) using a Vicorder. PA and ST were measured using hip-worn ActiGraph GT3X accelerometers. After adjusting for covariates, each additional 1000 steps per day was associated with a 0.038m/s lower cfPWV (95% CI=-0.076, 0.0003), 0.095 10(-3) kPa(-1) higher DC (95% CI=0.006, 0.185), 0.26% lower AIx (95% CI=-0.40, -0.12) and a 0.005mm lower CIMT (95% CI=-0.008, -0.001). Moderate and vigorous PA (MVPA) was associated with lower AIx and CIMT, light PA (LPA) with lower cfPWV and CIMT and ST with higher cfPWV, AIx and CIMT and lower DC. LPA and ST were highly correlated (r=-0.62). The independence of MVPA and ST or MVPA and LPA was inconsistent across vascular measures. Bout lengths for both PA and ST were not associated with vascular measures. In our cross-sectional study of older men, all PA regardless of intensity or bout duration was beneficially associated with vascular measures, as was lower ST. LPA was particularly relevant for cfPWV and CIMT

A novel accelerometer-based method to describe day-to-day exposure to potentially osteogenic vertical impacts in older adults: findings from a multi-cohort study

Summary: This observational study assessed vertical impacts experienced in older adults as part of their day-to-day physical activity using accelerometry and questionnaire data. Population-based older adults experienced very limited high-impact activity. The accelerometry method utilised appeared to be valid based on comparisons between different cohorts and with self-reported activity. Introduction: We aimed to validate a novel method for evaluating day-to-day higher impact weight-bearing physical activity (PA) in older adults, thought to be important in protecting against osteoporosis, by comparing results between four cohorts varying in age and activity levels, and with self-reported PA levels. Methods: Participants were from three population-based cohorts, MRC National Survey of Health and Development (NSHD), Hertfordshire Cohort Study (HCS) and Cohort for Skeletal Health in Bristol and Avon (COSHIBA), and the Master Athlete Cohort (MAC). Y-axis peaks (reflecting the vertical when an individual is upright) from a triaxial accelerometer (sampling frequency 50 Hz, range 0–16 g) worn at the waist for 7 days were classified as low (0.5–1.0 g), medium (1.0–1.5 g) or higher (≥1.5 g) impacts. Results: There were a median of 90, 41 and 39 higher impacts/week in NSHD (age 69.5), COSHIBA (age 76.8) and HCS (age 78.5) participants, respectively (total n = 1512). In contrast, MAC participants (age 68.5) had a median of 14,322 higher impacts/week. In the three population cohorts combined, based on comparison of beta coefficients, moderate-high-impact activities as assessed by PA questionnaire were suggestive of stronger association with higher impacts from accelerometers (0.25 [0.17, 0.34]), compared with medium (0.18 [0.09, 0.27]) and low impacts (0.13 [0.07,0.19]) (beta coefficient, with 95 % CI). Likewise in MAC, reported moderate-high-impact activities showed a stronger association with higher impacts (0.26 [0.14, 0.37]), compared with medium (0.14 [0.05, 0.22]) and low impacts (0.03 [−0.02, 0.08]). Conclusions: Our new accelerometer method appears to provide valid measures of higher vertical impacts in older adults. Results obtained from the three population-based cohorts indicate that older adults generally experience very limited higher impact weight-bearing PA

Identification and single-base gene-editing functional validation of a cis-EPO variant as a genetic predictor for EPO-increasing therapies

Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are currently under clinical development for treating anemia in chronic kidney disease (CKD), but it is important to monitor their cardiovascular safety. Genetic variants can be used as predictors to help inform the potential risk of adverse effects associated with drug treatments. We therefore aimed to use human genetics to help assess the risk of adverse cardiovascular events associated with therapeutically altered EPO levels to help inform clinical trials studying the safety of HIF-PHIs. By performing a genome-wide association meta-analysis of EPO (n = 6,127), we identified a cis-EPO variant (rs1617640) lying in the EPO promoter region. We validated this variant as most likely causal in controlling EPO levels by using genetic and functional approaches, including single-base gene editing. Using this variant as a partial predictor for therapeutic modulation of EPO and large genome-wide association data in Mendelian randomization tests, we found no evidence (at p < 0.05) that genetically predicted long-term rises in endogenous EPO, equivalent to a 2.2-unit increase, increased risk of coronary artery disease (CAD, OR [95% CI] = 1.01 [0.93, 1.07]), myocardial infarction (MI, OR [95% CI] = 0.99 [0.87, 1.15]), or stroke (OR [95% CI] = 0.97 [0.87, 1.07]). We could exclude increased odds of 1.15 for cardiovascular disease for a 2.2-unit EPO increase. A combination of genetic and functional studies provides a powerful approach to investigate the potential therapeutic profile of EPO-increasing therapies for treating anemia in CKD