Utility of international normative 20 m shuttle run values for identifying youth at increased cardiometabolic risk

The purpose of this study was to examine the ability of international normative centiles for the 20 m shuttle run test (20mSRT) to identify youth at increased cardiometabolic risk. This was a cross-sectional study involving 961 children aged 10–17 years (53% girls) from the United Kingdom. Receiver operating characteristic (ROC) curves determined the discriminatory ability of cardiorespiratory fitness percentiles for predicting increased cardiometabolic risk. ROC analysis demonstrated a significant but poor discriminatory accuracy of cardiorespiratory fitness in identifying low/high cardiometabolic risk in girls (AUC = 0.58, 95% CI: 0.54–0.63; p = 0.04), and in boys (AUC = 0.59, 95% CI: 0.54–0.63; p = 0.03). The cardiorespiratory fitness cut-off associated with high cardiometabolic risk was the 55th percentile (sensitivity = 33.3%; specificity = 84.5%) in girls and the 60th percentile (sensitivity = 42.9%; specificity = 73.6%) in boys. These 20mSRT percentile thresholds can be used to identify children and adolescents who may benefit from lifestyle intervention. Nonetheless, further work involving different populations and cardiometabolic risk scores comprising of different variables are needed to confirm our initial findings

Clinical progress and pharmacology of small molecule bromodomain inhibitors

Bromodomains have emerged as an exciting target class for drug discovery over the past decade. Research has primarily focused on the bromodomain and extra terminal (BET) family of bromodomains, which has led to the development of multiple small molecule inhibitors and an increasing number of clinical assets. The excitement centred on the clinical potential of BET inhibition has stimulated intense interest in the broader family and the growing number of non-BET bromodomain chemical probes has facilitated phenotypic investigations, implicating these targets in a variety of disease pathways including cancer, inflammation, embryonic development and neurological disorders

Does ratification of human-rights treaties have effects on population health?

Human-rights treaties indicate a country's commitment to human rights. Here, we assess whether ratification of human-rights treaties is associated with improved health and social indicators. Data for health (including HIV prevalence, and maternal, infant, and child [<5 years] mortalities) and social indicators (child labour, human development index, sex gap, and corruption index), gathered from 170 countries, showed no consistent associations between ratification of human-rights treaties and health or social outcomes. Established market economy states had consistently improved health compared with less wealthy settings, but this was not associated with treaty ratification. The status of treaty ratification alone is not a good indicator of the realisation of the right to health. We suggest the need for stringent requirements for ratification of treaties, improved accountability mechanisms to monitor compliance of states with treaty obligations, and financial assistance to support the realisation of the right to health

Advancements in the development of non-BET bromodomain chemical probes

The bromodomain and extra terminal (BET) family of bromodomain‐containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high‐quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non‐BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non‐BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non‐BET bromodomains as tractable therapeutic targets

Crystal structures and proton dynamics in potassium and cesium hydrogen bistrifluoroacetate salts with strong symmetric hydrogen bonds

The crystal structures of potassium and cesium bistrifluoroacetates were determined at room temperature and at 20 K and 14 K, respectively, with the single crystal neutron diffraction technique. The crystals belong to the I2/a and A2/a monoclinic space groups, respectively, and there is no visible phase transition. For both crystals, the trifluoroacetate entities form dimers linked by very short hydrogen bonds lying across a centre of inversion. Any proton disorder or double minimum potential can be rejected. The inelastic neutron scattering spectral profiles in the OH stretching region between 500 and 1000 cm^{-1} previously published [Fillaux and Tomkinson, Chem. Phys. 158 (1991) 113] are reanalyzed. The best fitting potential has the major characteristics already reported for potassium hydrogen maleate [Fillaux et al. Chem. Phys. 244 (1999) 387]. It is composed of a narrow well containing the ground state and a shallow upper part corresponding to dissociation of the hydrogen bond.Comment: 31 pages, 7 figure

Test-retest reliability of TRIMP in collegiate ice hockey players

The utility of the heart rate derived variable TRaining IMPulse (TRIMP) for assessing internal training load in ice hockey players is not clear. Having a reliable measure of internal training load during on-ice training sessions would help coaches program exercise training. This study determined the reliability of TRIMP during on-ice training sessions in ice hockey players. Twelve Division I collegiate male ice hockey players (aged 18–23 years) had their heart rate (HR) data recorded during two on-ice practice sessions separated by two weeks. TRIMP and other descriptive HR variables were compared between sessions. TRIMP demonstrated moderate reliability during on-ice sessions. Systematic error, quantified as standardized change in means was negligible (–0.19); random error quantified as the percent typical error (%TE) was moderate (12.2%); and, test-retest correlation was very strong (0.75). TRIMP is suitable for quantifying training load during intermittent work in hockey athletes. The results from our study can be used to determine the threshold for meaningful change in TRIMP, which may aid in informing decisions by coaches and strength training staff regarding on-ice training session difficulty and composition

Alkene syn- and anti-oxyamination with malonoyl peroxides

Malonoyl peroxide [6] is an effective reagent for the syn- or anti-oxyamination of alkenes. Reaction of [6] and an alkene in the presence of O-tert-butyl-N-tosylcarbamate (R3 = CO2tBu) leads to the anti-oxyaminated product in up to 99% yield. Use of O-methyl-N-tosyl carbamate (R3 = CO2Me) as the nitrogen nucleophile followed by treatment of the product with trifluoroacetic acid leads to the syn-oxyaminated product in up to 77% yield. Mechanisms consistent with the observed selectivities are proposed

International normative 20 m shuttle run values from 1 142 026 children and youth representing 50 countries

Objective To develop sex-specific and age-specific international norms for the 20 m shuttle run test (20mSRT) in children and youth (aged 9–17 years), and to estimate the prevalence meeting the FITNESSGRAM criterion-referenced standards for healthy cardiorespiratory endurance (CRE). Methods A systematic review was undertaken to identify papers explicitly reporting descriptive 20mSRT (with 1 min stages) data on children and youth since 1981. Data were included on apparently healthy (free from known disease/injury) 9–17 years old. Following standardisation to a common metric and for protocol differences, pseudo data were generated using Monte Carlo simulation, with population-weighted sex-specific and age-specific normative centiles generated using the Lambda Mu and Sigma (LMS) method. Sex-related and age-related differences were expressed as per cent and standardised differences in means. The prevalence with healthy CRE was estimated using the sex-specific and age-specific FITNESSGRAM criterion-referenced standards for . Results Norms were displayed as tabulated centiles and as smoothed centile curves for the 20mSRT using 4 common metrics (speed at the last completed stage, completed stages/minutes, laps and relative ). The final data set included 1 142 026 children and youth from 50 countries, extracted from 177 studies. Boys consistently outperformed girls at each age group (mean difference±95% CI: 0.86±0.28 km/h or 0.79±0.20 standardised units), with the magnitude of age-related increase larger for boys than for girls. A higher proportion of boys (mean±95% CI: 67±14%) had healthy CRE than girls (mean±95% CI: 54±17%), with the prevalence of healthy CRE decreasing systematically with age. Conclusions This study provides the most comprehensive and up-to-date set of international sex-specific and age-specific 20mSRT norms for children and youth, which have utility for health and fitness screening, profiling, monitoring and surveillance

Australia and Other Nations are Failing to Meet Sedentary Behaviour Guidelines for Children: Implications and a Way Forward

BACKGROUND: Australia has joined a growing number of nations which have evaluated the physical activity and sedentary behaviour status of their children. Australia received a 'D minus' in the first Active Healthy Kids Australia Physical Activity Report Card. METHODS: An expert subgroup of the Australian Report Card Research Working Group iteratively reviewed available evidence to answer three questions: 1) What are the main sedentary behaviours of children?, 2) What are the potential mechanisms for sedentary behaviour to impact on child health and development? and, 3) What are the effects of different types of sedentary behaviours on child health and development? RESULTS: Neither sedentary time nor screen time are homogeneous activities likely to result in homogenous effects. There are several mechanisms by which various sedentary behaviours may positively or negatively affect cardiometabolic, neuro-musculoskeletal, and psycho-social health, though the strength of evidence varies. National surveillance systems, and mechanistic, longitudinal and experimental studies are needed for Australia and other nations to improve their grade. CONCLUSIONS: Despite limitations, available evidence is sufficiently convincing that the total exposure and pattern of exposure to sedentary behaviours are critical to the healthy growth, development and wellbeing of children. Nations therefore need strategies to address these common behaviours