What if all children achieved WHO recommendations on physical activity? Estimating the impact on socioeconomic inequalities in childhood overweight in the UK Millennium Cohort Study

Background: The World Health organization (WHO) recommends that children engage in 60 min daily moderate-to-vigorous physical activity (dMVPA). Just half of children in the UK achieve these levels (with similarly low levels in other high-income countries). Thus, the dMVPA target is a focus of national obesity strategies. However, the potential impact of increased physical activity on prevalence and inequalities in childhood overweight is unknown. Using objective data from the Millennium Cohort Study (∼18 000 children born 2000–02) we simulated a series of hypothetical physical activity intervention scenarios: achievement of the target, and more realistic increases demonstrated in trials. Methods: Predicted probabilities of overweight and obesity (using measured heights and weights at age 11) were estimated in multinomial marginal structural models, adjusting for dMVPA (measured with accelerometers at age 7) and confounding. Inequalities were assessed according to household income quintiles [risk ratios (RRs) and risk differences (RDs)]. Intervention scenarios were simulated by re-estimating predicted probabilities of overweight/obesity after manipulating (increasing) dMVPA by varying amounts, for different eligibility criteria and with varying uptake. Analyses included 6493 children with accelerometer data. Survey weights and multiple imputation addressed sampling design, attrition and item missingness. Results: In all, 27% children were overweight/obese, with relative and absolute inequalities in the expected direction; 51% children were achieving 60 min dMVPA, with those from the lowest income quintile achieving, on average, 3 min more dMVPA than those from the highest income quintile. A simulation of universal achievement of the dMVPA target reduced the prevalence of overweight/obesity to 22%, but increased relative inequalities (absolute inequalities were unchanged). Smaller increases in dMVPA (informed by intervention evidence) did little to reduce prevalence or inequalities, even when targeting high-risk groups. Conclusions: Universal achievement of the WHO dMVPA target, if attainable, would reduce prevalence of childhood overweight and obesity but not inequalities. Scale-up of more realistic interventions would have limited impact

PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.

BACKGROUND: Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for patients who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) may further reduce LDL-C, potentially reducing CVD risk as well. OBJECTIVES: Primary To quantify short-term (24 weeks), medium-term (one year), and long-term (five years) effects of PCSK9 inhibitors on lipid parameters and on the incidence of CVD. Secondary To quantify the safety of PCSK9 inhibitors, with specific focus on the incidence of type 2 diabetes, cognitive function, and cancer. Additionally, to determine if specific patient subgroups were more or less likely to benefit from the use of PCSK9 inhibitors. SEARCH METHODS: We identified studies by systematically searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Web of Science. We also searched Clinicaltrials.gov and the International Clinical Trials Registry Platform and screened the reference lists of included studies. We identified the studies included in this review through electronic literature searches conducted up to May 2016, and added three large trials published in March 2017. SELECTION CRITERIA: All parallel-group and factorial randomised controlled trials (RCTs) with a follow-up time of at least 24 weeks were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed and extracted data. When data were available, we calculated pooled effect estimates. MAIN RESULTS: We included 20 studies with data on 67,237 participants (median age 61 years; range 52 to 64 years). Twelve trials randomised participants to alirocumab, three trials to bococizumab, one to RG7652, and four to evolocumab. Owing to the small number of trials using agents other than alirocumab, we did not differentiate between types of PCSK9 inhibitors used. We compared PCSK9 inhibitors with placebo (thirteen RCTs), ezetimibe (two RCTs) or ezetimibe and statins (five RCTs).Compared with placebo, PCSK9 inhibitors decreased LDL-C by 53.86% (95% confidence interval (CI) 58.64 to 49.08; eight studies; 4782 participants; GRADE: moderate) at 24 weeks; compared with ezetimibe, PCSK9 inhibitors decreased LDL-C by 30.20% (95% CI 34.18 to 26.23; two studies; 823 participants; GRADE: moderate), and compared with ezetimibe and statins, PCSK9 inhibitors decreased LDL-C by 39.20% (95% CI 56.15 to 22.26; five studies; 5376 participants; GRADE: moderate).Compared with placebo, PCSK9 inhibitors decreased the risk of CVD events, with a risk difference (RD) of 0.91% (odds ratio (OR) of 0.86, 95% CI 0.80 to 0.92; eight studies; 59,294 participants; GRADE: moderate). Compared with ezetimibe and statins, PCSK9 inhibitors appeared to have a stronger protective effect on CVD risk, although with considerable uncertainty (RD 1.06%, OR 0.45, 95% CI 0.27 to 0.75; three studies; 4770 participants; GRADE: very low). No data were available for the ezetimibe only comparison. Compared with placebo, PCSK9 probably had little or no effect on mortality (RD 0.03%, OR 1.02, 95% CI 0.91 to 1.14; 12 studies; 60,684 participants; GRADE: moderate). Compared with placebo, PCSK9 inhibitors increased the risk of any adverse events (RD 1.54%, OR 1.08, 95% CI 1.04 to 1.12; 13 studies; 54,204 participants; GRADE: low). Similar effects were observed for the comparison of ezetimibe and statins: RD 3.70%, OR 1.18, 95% CI 1.05 to 1.34; four studies; 5376 participants; GRADE: low. Clinical event data were unavailable for the ezetimibe only comparison. AUTHORS' CONCLUSIONS: Over short-term to medium-term follow-up, PCSK9 inhibitors reduced LDL-C. Studies with medium-term follow-up time (longest median follow-up recorded was 26 months) reported that PCSK9 inhibitors (compared with placebo) decreased CVD risk but may have increased the risk of any adverse events (driven by SPIRE-1 and -2 trials). Available evidence suggests that PCSK9 inhibitor use probably leads to little or no difference in mortality. Evidence on relative efficacy and safety when PCSK9 inhibitors were compared with active treatments was of low to very low quality (GRADE); follow-up times were short and events were few. Large trials with longer follow-up are needed to evaluate PCSK9 inhibitors versus active treatments as well as placebo. Owing to the predominant inclusion of high-risk patients in these studies, applicability of results to primary prevention is limited. Finally, estimated risk differences indicate that PCSK9 inhibitors only modestly change absolute risks (often to less than 1%)

"The Collecting Itself Feels Good": Towards Collection Interfaces for Digital Game Objects

© Lennart Nacke, 2016. This is the author’s version of the work. It is posted here for your personal use. Not for redistribution. The definitive version was published in CHI PLAY Companion '16 Proceedings of the 2016 Annual Symposium on Computer-Human Interaction in Play Companion Extended Abstracts, https://doi.org/10.1145/2967934.2968088Digital games offer a variety of collectible objects. We investigate players' collecting behaviors in digital games to determine what digital game objects players enjoyed collecting and why they valued these objects. Using this information, we seek to inform the design of future digital game object collection interfaces. We discuss the types of objects that players prefer, the reasons that players value digital game objects, and how collection behaviors may guide play. Through our findings, we identify design implications for digital game object collection interfaces: enable object curation, preserve rules and mechanics, preserve context of play, and allow players to share their collections with others. Digital game object collection interfaces are applicable to the design of digital games, gamified applications, and educational software.Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada Social Sciences and Humanities Research Council of CanadaPeer-reviewe

Physical activity among children with asthma: Cross‐sectional analysis in the UK millennium cohort

Background: Although beneficial for health and well‐being, most children do not achieve recommended levels of physical activity. Evidence for children with asthma is mixed, with symptom severity rarely considered. This paper aimed to address this gap. Methods: We analyzed cross‐sectional associations between physical activity and parent‐reported asthma symptoms and severity for 6497 UK Millennium Cohort Study 7−year‐old participants (3321, [49%] girls). Primary outcomes were daily moderate‐to‐vigorous physical activity (MVPA, minutes) and proportion of children achieving recommended minimum daily levels of 60 minutes of MVPA. Daily steps, sedentary time, and total activity counts per minute (cpm) were recorded, as were parent‐reported asthma symptoms, medications, and recent hospital admissions. Associations were investigated using quantile (continuous outcomes) and Poisson (binary outcomes) regression, adjusting for demographic, socioeconomic, health, and environmental factors. Results: Neither asthma status nor severity was associated with MVPA; children recently hospitalized for asthma were less likely to achieve recommended daily MVPA (risk ratio [95% confidence interval [CI]]: 0.67 [0.44, 1.03]). Recent wheeze, current asthma, and severe asthma symptoms were associated with fewer sedentary hours (difference in medians [95% CI]: −0.18 [−0.27, −0.08]; −0.14 [−0.24, −0.05]; −0.15, [−0.28, −0.02], respectively) and hospital admission with lower total activity (−48 cpm [−68, −28]). Conclusion: Children with asthma are as physically active as their asthma‐free counterparts, while those recently hospitalized for asthma are less active. Qualitative studies are needed to understand the perceptions of children and families about physical activity following hospital admission and to inform support and advice needed to maintain active lifestyles for children with asthma

Feedback and metal enrichment in cosmological SPH simulations I. A model for chemical enrichment

We discuss a model for treating chemical enrichment by SNII and SNIa explosions in simulations of cosmological structure formation. Our model includes metal-dependent radiative cooling and star formation in dense collapsed gas clumps. Metals are returned into the diffuse interstellar medium by star particles using a local SPH smoothing kernel. A variety of chemical abundance patterns in enriched gas arise in our treatment owing to the different yields and lifetimes of SNII and SNIa progenitor stars. In the case of SNII chemical production, we adopt metal-dependent yields. Because of the sensitive dependence of cooling rates on metallicity, enrichment of galactic haloes with metals can in principle significantly alter subsequent gas infall and the build up of the stellar components. Indeed, in simulations of isolated galaxies we find that a consistent treatment of metal-dependent cooling produces 25% more stars outside the central region than simulations with a primordial cooling function. In the highly-enriched central regions, the evolution of baryons is however not affected by metal cooling, because here the gas is always dense enough to cool. A similar situation is found in cosmological simulations because we include no strong feedback processes which could spread metals over large distances and mix them into unenriched diffuse gas. We demonstrate this explicitly with test simulations which adopt super-solar cooling functions leading to large changes both in the stellar mass and in the metal distributions. We also find that the impact of metallicity on the star formation histories of galaxies may depend on their particular evolutionary history. Our results hence emphasise the importance of feedback processes for interpreting the cosmic metal enrichment.Comment: 15 pages, 15 figures, MNRAS, modified to match published versio

Close Binary System GO Cyg

In this study, we present long term photometric variations of the close binary system \astrobj{GO Cyg}. Modelling of the system shows that the primary is filling Roche lobe and the secondary of the system is almost filling its Roche lobe. The physical parameters of the system are $M_1 = 3.0\pm0.2 M_{\odot}$, $M_2 = 1.3 \pm 0.1 M_{\odot}$, $R_1 = 2.50\pm 0.12 R_{\odot}$, $R_2 = 1.75 \pm 0.09 R_{\odot}$, $L_1 = 64\pm 9 L_{\odot}$, $L_2 = 4.9 \pm 0.7 L_{\odot}$, and $a = 5.5 \pm 0.3 R_{\odot}$. Our results show that \astrobj{GO Cyg} is the most massive system near contact binary (NCB). Analysis of times of the minima shows a sinusoidal variation with a period of $92.3\pm0.5$ years due to a third body whose mass is less than 2.3$M_{\odot}$. Finally a period variation rate of $-1.4\times10^{-9}$ d/yr has been determined using all available light curves.Comment: Accepted for publication in New Astronomy, 18 pages, 4 figures, 7 table

Nematode Symbiont for Photorhabdus asymbiotica

Photorhabdus asymbiotica is an emerging bacterial pathogen that causes locally invasive soft tissue and disseminated bacteremic infections in the United States and Australia. Although the source of infection was previously unknown, we report that the bacterium is found in a symbiotic association with an insect-pathogenic soil nematode of the genus Heterorhabditis

Could Greater Physical Activity Reduce Population Prevalence and Socioeconomic Inequalities in Children’s Mental Health Problems? A Policy Simulation

Background: One in four children aged 5-16 years (y) shows signs of mental health problems in the UK; risk is higher in economically disadvantaged groups. Greater physical activity is associated with lower risk of internalizing problems such as depression and anxiety. We simulated the potential impact of population-wide physical activity interventions on overall prevalence of internalizing problems, and by family income. Interventions were based on the World Health Organization (WHO) children’s target of 60 minutes (min) of moderate-to-vigorous physical activity per day and trial evidence. Methods: Data were from the UK Millennium Cohort Study, a population-representative cohort of children born in 2000-2002. Household income (5y) was the exposure; internalizing problems (outcome) were measured using the Strengths and Difficulties Questionnaire (11y). Of 18,296 singletons, 6,497 had accelerometer physical activity data (mediator, manipulated to simulate interventions) at 7y. We predicted probabilities of outcome according to exposure in marginal structural models, weighted for attrition and confounding, and adjusted for observed mediator. We then re-estimated probabilities in different physical activity intervention scenarios, assessing income inequalities in internalizing problems with risk ratios (RRs) and differences (RDs) according to income quintile. Results: Simulating universal achievement of the WHO target led to little change in prevalence (10% [95% CI: 8%,12%]) and socioeconomic inequalities in internalizing problems; RR: 2.2 (1.1, 3.4); RD: 8% [5%,13%]). More modest increases in physical activity achieved weaker results. Conclusion: Our simulations suggest that large increases in moderate-to-vigorous physical activity in the UK would have little effect on prevalence and inequalities in child mental health problems

An Ecological Study of COVID-19 Infection Rates within the UK Food and Drink Processing Industry.

OBJECTIVES: Food processing facilities represent critical infrastructure that have stayed open during much of the COVID-19 pandemic. Understanding the burden of COVID-19 in this sector is thus important to help reduce the potential for workplace infection in future outbreaks. METHODS: We undertook a workplace survey in the UK food and drink processing sector and collected information on workplace size, characteristics (e.g. temperature, ventilation), and experience with COVID-19 (e.g. numbers of positive cases). For each site, we calculated COVID-19 case rates per month per 1000 workers. We performed an ecological analysis using negative binomial regression to assess the association between COVID-19 rates and workplace and local risk factors. RESULTS: Respondents from 33 companies including 66 individual sites completed the survey. COVID-19 cases were reported from the start of the pandemic up to June 2021. Respondents represented a range of industry subgroups, including grain milling/storage (n = 16), manufacture of malt (n = 14), manufacture of prepared meals (n = 12), manufacture of beverages (n = 8), distilling (n = 5), manufacture of baked goods (n = 5), and other (n = 6), with a total of 15 563 workers across all sites. Average monthly case rates per 1000 workers ranged from 0.9 in distilling to 6.1 in grain milling/storage. Incidence rate ratios were partially attenuated after adjusting for several local and workplace factors, though risks for one subgroup (grain milling/storage) remained elevated. Certain local and workplace characteristics were related to higher infection rates, such as higher deprivation (5 km only), a lower proportion of remote workers, lower proportion of workers in close proximity, and higher numbers of workers overall. CONCLUSIONS: Our analysis suggests some heterogeneity in the rates of COVID-19 across sectors of the UK food and drink processing industry. Infection rates were associated with deprivation, the proportions of remote workers and workers in close proximity, and the number of workers