Prevalence of gambling behaviours and their associations with socioemotional harm among 11-16 year olds in Wales: findings from the School Health Research Network survey

This is the final version. Available on open access from OUP via the DOI in this recordBACKGROUND: Gambling opportunities are increasingly available and acceptable to many adolescents. Adolescent problem gambling has been associated with poor outcomes, such as lower reported physical and mental health. While much research has focussed on 'problem' gambling, analysing the distribution and determinants of experimentation with gambling is important in order to understand its normalization and population level consequences. This study describes the distribution of inequalities and socioemotional harms associated with adolescent gambling. METHODS: Data were drawn from a subsample of students (N = 37 363) who completed gambling questions as part of the 2017 School Health Research Network Student Health and Wellbeing Survey, representing 193 secondary schools in Wales. Using imputations, we estimated a series of single-predictor and multi-predictor regressions for count of gambling behaviours, any gambling in the past 12 months and socioemotional harms of gambling. RESULTS: Approximately two-fifths (41.0%) of respondents reported gambling in the past 12 months, of whom 16.2% reported feeling bad as a result of their own gambling. We found significant sex differences in gambling, with boys gambling more frequently than girls. Adolescents from more affluent families reported a higher count of gambling behaviours and socioemotional harms, although paradoxically, increasing affluence was also associated with lower prevalence of gambling in the last year. Non-White British ethnicities and students who felt less connected to school were more likely to engage in gambling and experience socioemotional harms. CONCLUSIONS: Our findings provide important new insights regarding risk factors in adolescence associated with gambling behaviours and socioemotional harms.British Heart FoundationCancer Research UKEconomic and Social Research Council (ESRC)Medical Research Council (MRC)Welsh GovernmentWellcome Trus

Dating and relationship violence victimization and perpetration among 11-16 year olds in Wales: a cross-sectional analysis of the School Health Research Network (SHRN) survey

This is the final version. Available on open access from OUP via the DOI in this recordBACKGROUND: This study examines the prevalence of dating and relationship violence (DRV) victimization, perpetration and joint victimization and perpetration, and associations between DRV and socio-demographic characteristics. METHODS: Cross-sectional self-report data from 74 908 students aged 11-16 from 193 schools across Wales were collected and analysed using generalized estimating equations to examine prevalence and predictors of emotional and physical DRV victimization, perpetration and joint victimization and perpetration. RESULTS: More girls reported emotional victimization (28%) and perpetration (18%) than boys (20% and 16%, respectively). More girls (8%) than boys (7%) reported physical perpetration. However, boys (17%) reported more physical victimization than girls (12%). Age-related trajectories of DRV victimization and perpetration were stronger in girls than in boys. Students from single or step parent homes, those in care, and certain ethnic minority groups had increased odds of DRV. No association was found between socioeconomic status and DRV. CONCLUSIONS: Age-related trajectories and the lack of social patterning by socioeconomic status point to the value of early, universal interventions, while some evidence of ethnic patterning and family structure-related risk factors suggest areas for further research and targeted interventions. DRV continues to be a major public health problem for which little UK-specific intervention evidence exists.British Heart FoundationCancer Research UKEconomic and Social Research Council (ESRC)Medical Research Council (MRC)Welsh GovernmentWellcome Trus

Reduced physical activity in young and older adults: metabolic and musculoskeletal implications

Background: Although the health benefits of regular physical activity and exercise are well established and have been incorporated into national public health recommendations, there is a relative lack of understanding pertaining to the harmful effects of physical inactivity. Experimental paradigms including complete immobilization and bed rest are not physiologically representative of sedentary living. A useful ‘real-world’ approach to contextualize the physiology of societal downward shifts in physical activity patterns is that of short-term daily step reduction. Results: Step-reduction studies have largely focused on musculoskeletal and metabolic health parameters, providing relevant disease models for metabolic syndrome, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), sarcopenia and osteopenia/osteoporosis. In untrained individuals, even a short-term reduction in physical activity has a significant impact on skeletal muscle protein and carbohydrate metabolism, causing anabolic resistance and peripheral insulin resistance, respectively. From a metabolic perspective, short-term inactivity-induced peripheral insulin resistance in skeletal muscle and adipose tissue, with consequent liver triglyceride accumulation, leads to hepatic insulin resistance and a characteristic dyslipidaemia. Concomitantly, various inactivity-related factors contribute to a decline in function; a reduction in cardiorespiratory fitness, muscle mass and muscle strength. Conclusions: Physical inactivity maybe particularly deleterious in certain patient populations, such as those at high risk of T2D or in the elderly, considering concomitant sarcopenia or osteoporosis. The effects of short-term physical inactivity (with step reduction) are reversible on resumption of habitual physical activity in younger people, but less so in older adults. Nutritional interventions and resistance training offer potential strategies to prevent these deleterious metabolic and musculoskeletal effects. Impact: Individuals at high risk of/with cardiometabolic disease and older adults may be more prone to these acute periods of inactivity due to acute illness or hospitalization. Understanding the risks is paramount to implementing countermeasures

Developing methods for the overarching synthesis of quantitative and qualitative evidence: the interweave synthesis approach

This is the author accepted manuscript. The final version is available on open access from Wiley via the DOI in this recordThe incorporation of evidence derived from multiple research designs into one single synthesis can enhance the utility of systematic reviews making them more worthwhile, useful and insightful. Methodological guidance for mixed-methods synthesis continues to emerge and evolve but broadly involves a sequential, parallel or convergent approach according to the degree of independence between individual syntheses before they are combined.We present two case studies in which we used novel and innovative methods to draw together the findings from individual but related quantitative and qualitative syntheses to aid interpretation of the overall evidence base. Our approach moved beyond making a choice between parallel, sequentialor convergent methods to interweave the findings of individual reviews and offers three key innovations to mixed-methods synthesis methods: i)The use of intersubjective questions to understand the findings of the individual reviews through different lenses, ii)Immersion of key reviewers in the entirety of the evidence base, and iii)Commencing the process during the final stages of the synthesis of individual reviews, at a point where reviewers are developing an understanding of initial findings. Underlying our approachis the process of exploration and identification of links between and across review findings; an approach that is fundamental to all evidence syntheses but usually occurs at the level of the study. Adapting existing methods for exploring and identifying patterns and links between and across studies to interweave the findings between and across reviews may prove valuable.NIHR Health Technology Assessment Programm

Functional characterisation of substrate-binding proteins to address nutrient uptake in marine picocyanobacteria.

Marine cyanobacteria are key primary producers, contributing significantly to the microbial food web and biogeochemical cycles by releasing and importing many essential nutrients cycled through the environment. A subgroup of these, the picocyanobacteria (Synechococcus and Prochlorococcus), have colonised almost all marine ecosystems, covering a range of distinct light and temperature conditions, and nutrient profiles. The intra-clade diversities displayed by this monophyletic branch of cyanobacteria is indicative of their success across a broad range of environments. Part of this diversity is due to nutrient acquisition mechanisms, such as the use of high-affinity ATP-binding cassette (ABC) transporters to competitively acquire nutrients, particularly in oligotrophic (nutrient scarce) marine environments. The specificity of nutrient uptake in ABC transporters is primarily determined by the peripheral substrate-binding protein (SBP), a receptor protein that mediates ligand recognition and initiates translocation into the cell. The recent availability of large numbers of sequenced picocyanobacterial genomes indicates both Synechococcus and Prochlorococcus apportion >50% of their transport capacity to ABC transport systems. However, the low degree of sequence homology among the SBP family limits the reliability of functional assignments using sequence annotation and prediction tools. This review highlights the use of known SBP structural representatives for the uptake of key nutrient classes by cyanobacteria to compare with predicted SBP functionalities within sequenced marine picocyanobacteria genomes. This review shows the broad range of conserved biochemical functions of picocyanobacteria and the range of novel and hypothetical ABC transport systems that require further functional characterisation

Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?

BACKGROUND: Early identification of patients with drug-resistant tuberculosis (DR-TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss. METHODS: A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB. RESULTS: Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9). CONCLUSIONS: Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority

AMPK and uterine artery vasodilation

Genes near adenosine monophosphate-activated protein kinase-α1 (PRKAA1) have been implicated in the greater uterine artery (UtA) blood flow and relative protection from fetal growth restriction seen in altitude-adapted Andean populations. Adenosine monophosphate-activated protein kinase (AMPK) activation vasodilates multiple vessels but whether AMPK is present in UtA or placental tissue and influences UtA vasoreactivity during normal or hypoxic pregnancy remains unknown. We studied isolated UtA and placenta from near-term C57BL/6J mice housed in normoxia (n = 8) or hypoxia (10% oxygen, n = 7-9) from day 14 to day 19, and placentas from non-labouring sea level (n = 3) or 3100 m (n = 3) women. Hypoxia increased AMPK immunostaining in near-term murine UtA and placental tissue. RT-PCR products for AMPK-α1 and -α2 isoforms and liver kinase B1 (LKB1; the upstream kinase activating AMPK) were present in murine and human placenta, and hypoxia increased LKB1 and AMPK-α1 and -α2 expression in the high- compared with low-altitude human placentas. Pharmacological AMPK activation by A769662 caused phenylephrine pre-constricted UtA from normoxic or hypoxic pregnant mice to dilate and this dilatation was partially reversed by the NOS inhibitor l-NAME. Hypoxic pregnancy sufficient to restrict fetal growth markedly augmented the UtA vasodilator effect of AMPK activation in opposition to PE constriction as the result of both NO-dependent and NO-independent mechanisms. We conclude that AMPK is activated during hypoxic pregnancy and that AMPK activation vasodilates the UtA, especially in hypoxic pregnancy. AMPK activation may be playing an adaptive role by limiting cellular energy depletion and helping to maintain utero-placental blood flow in hypoxic pregnancy.Funding for these studies was provided by the Wellcome Trust (084804/2/08/Z) to G.J.B., the British Heart Foundation and the Wellcome Trust to D.A.G., the Biotechnology and Biological Sciences Research Council (BBSRC) to A.L.F., a UK Wellcome Trust Programme Grant (WT081195MA) to A.M.E. and A.D.M., a BBSRC studentship and in vivo skills award to J.S.H., a National Health Medical Research Council and Centre for Trophoblast Research fellowship to A.N.S.-P., and a NIH RO1 grant (HLBI-079647) to L.G.M. along with sabbatical support from Wake Forest University.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1113/JP27099

Hard and easy instances of L-Tromino tilings

In this work we study tilings of regions in the square lattice with L-shaped trominoes. Deciding the existence of a tiling with L-trominoes for an arbitrary region in general is NP-complete, nonetheless, we identify restrictions to the problem where it either remains NP-complete or has a polynomial time algorithm. First, we characterize the possibility of when an Aztec rectangle has an L-tromino tiling, and hence also an Aztec diamond; if an Aztec rectangle has an unknown number of defects or holes, however, the problem of deciding a tiling is NP-complete. Then, we study tilings of arbitrary regions where only 180∘ rotations of L-trominoes are available. For this particular case we show that deciding the existence of a tiling remains NP-complete; yet, if a region does not contain so-called “forbidden polyominoes” as subregions, then there exists a polynomial time algorithm for deciding a tiling

Sperm death and dumping in Drosophila

Mating with more than one male is the norm for females of many species. In addition to generating competition between the ejaculates of different males, multiple mating may allow females to bias sperm use. In Drosophila melanogaster, the last male to inseminate a female sires approximately 80% of subsequent progeny. Both sperm displacement, where resident sperm are removed from storage by the incoming ejaculate of the copulating male, and sperm incapacitation, where incoming seminal fluids supposedly interfere with resident sperm, have been implicated in this pattern of sperm use. But the idea of incapacitation is problematic because there are no known mechanisms by which an individual could damage rival sperm and not their own. Females also influence the process of sperm use, but exactly how is unclear. Here we show that seminal fluids do not kill rival sperm and that any 'incapacitation' is probably due to sperm ageing during sperm storage. We also show that females release stored sperm from the reproductive tract (sperm dumping) after copulation with a second male and that this requires neither incoming sperm nor seminal fluids. Instead, males may cause stored sperm to be dumped or females may differentially eject sperm from the previous mating