408 research outputs found

    Model selection of the effect of binary exposures over the life course (Epidemiology (2015) 26 (719-726))

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    Epidemiologists are often interested in examining the effect on a later-life outcome of an exposure measured repeatedly over the life course. When different hypotheses for this effect are proposed by competing theories, it is important to identify those most supported by observed data as a first step toward estimating causal associations. One method is to compare goodness-of-fit of hypothesized models with a saturated model, but it is unclear how to judge the “best” out of two hypothesized models that both pass criteria for a good fit. We developed a new method using the least absolute shrinkage and selection operator to identify which of a small set of hypothesized models explains most of the observed outcome variation. We analyzed a cohort study with repeated measures of socioeconomic position (exposure) through childhood, early- and mid-adulthood, and body mass index (outcome) measured in mid-adulthood. We confirmed previous findings regarding support or lack of support for the following hypotheses: accumulation (number of times exposed), three critical periods (only exposure in childhood, early- or mid-adulthood), and social mobility (transition from low to high socioeconomic position). Simulations showed that our least absolute shrinkage and selection operator approach identified the most suitable hypothesized model with high probability in moderately sized samples, but with lower probability for hypotheses involving change in exposure or highly correlated exposures. Identifying a single, simple hypothesis that represents the specified knowledge of the life course association allows more precise definition of the causal effect of interest

    A robust mean and variance test with application to high-dimensional phenotypes

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    Most studies of continuous health-related outcomes examine differences in mean levels (location) of the outcome by exposure. However, identifying effects on the variability (scale) of an outcome, and combining tests of mean and variability (location-and-scale), could provide additional insights into biological mechanisms. A joint test could improve power for studies of high-dimensional phenotypes, such as epigenome-wide association studies of DNA methylation at CpG sites. One possible cause of heterogeneity of variance is a variable interacting with exposure in its effect on outcome, so a joint test of mean and variability could help in the identification of effect modifiers. Here, we review a scale test, based on the Brown-Forsythe test, for analysing variability of a continuous outcome with respect to both categorical and continuous exposures, and develop a novel joint location-and-scale score (JLSsc) test. These tests were compared to alternatives in simulations and used to test associations of mean and variability of DNA methylation with gender and gestational age using data from the Accessible Resource for Integrated Epigenomics Studies (ARIES). In simulations, the Brown-Forsythe and JLSsc tests retained correct type I error rates when the outcome was not normally distributed in contrast to the other approaches tested which all had inflated type I error rates. These tests also identified > 7500 CpG sites for which either mean or variability in cord blood methylation differed according to gender or gestational age. The Brown-Forsythe test and JLSsc are robust tests that can be used to detect associations not solely driven by a mean effect

    Extending the Arctic Sea Ice Freeboard and Sea Level Record with the Sentinel-3 Radar Altimeters

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    In February 2016 and April 2018 the European Space Agency launched the Sentinel-3A and 3B satellites respectively, as part of the European Commission’s multi-satellite Copernicus Programme. Here we process Sentinel-3A waveform data to estimate Arctic sea level anomaly and radar freeboard from November 2017 to April 2018. We compare our results to those from the CryoSat-2 satellite, and find an intermission bias on sea-level anomaly of 2 cm. We also find a mean radar freeboard difference of 1 cm, which we attribute to the use of empirical retrackers to retrieve lead and floe elevations. Ahead of Sentinel-3B waveform data being made available, we use orbit files to estimate the improvement in sampling resolution afforded by the addition of Sentinel-3A and 3B data to the CryoSat-2 dataset. By combining data from the three satellites, grid resolution or time-sampling can be almost tripled compared with using CryoSat-2 data alone

    Polygenic risk for depression, anxiety and neuroticism are associated with the severity and rate of change in depressive symptoms across adolescence

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    Background Adolescence marks a period where depression will commonly onset. Twin studies show that genetic influences play a role in how depression develops and changes across adolescence. Recent genome‐wide association studies highlight that common genetic variants – which can be combined into polygenic risk scores (PRS) – are also implicated in depression. However, the role of PRS in adolescent depression and changes in adolescent depression is not yet understood. We aimed to examine associations between PRS for five psychiatric traits and depressive symptoms measured across adolescence using cross‐sectional and growth‐curve models. The five PRS were as follows: depression (DEP), major depressive disorder (MDD), anxiety (ANX), neuroticism (NEU) and schizophrenia (SCZ). Methods We used data from over 6,000 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) to examine associations between the five PRS and self‐reported depressive symptoms (Short Mood and Feelings Questionnaire) over 9 occasions from 10 to 24 years. The PRS were created from well‐powered genome‐wide association studies conducted in adult populations. We examined cross‐sectional associations between the PRS at each age and then again with longitudinal trajectories of depressive symptoms in a repeated measures framework using multilevel growth‐curve analysis to examine the severity and the rate of change. Results There was strong evidence that higher PRS for DEP, MDD and NEU were associated with worse depressive symptoms throughout adolescence and into young adulthood in our cross‐sectional analysis, with consistent associations observed across all nine occasions. Growth‐curve analyses provided stronger associations (as measured by effect sizes) and additional insights, demonstrating that individuals with higher PRS for DEP, MDD and NEU had steeper trajectories of depressive symptoms across development, all with a greater increasing rate of change during adolescence. Evidence was less consistent for the ANX and SCZ PRS in the cross‐sectional analysis, yet there was some evidence for an increasing rate of change in adolescence in the growth‐curve analyses with the ANX PRS. Conclusions These results show that common genetic variants as indexed by varying psychiatric PRS show patterns of specificity that influence both the severity and rate of change in depressive symptoms throughout adolescence and then into young adulthood. Longitudinal data that make use of repeated measures designs have the potential to provide greater insights how genetic factors influence the onset and persistence of adolescent depression

    Socioeconomic differences in childhood length/height trajectories in a middle-income country: a cohort study:a cohort study

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    Published: 8 September 2014Socioeconomic disadvantage is associated with shorter adult stature. Few studies have examined socioeconomic differences in stature from birth to childhood and the mechanisms involved, particularly in middle-income former Soviet settings.The sample included 12,463 Belarusian children (73% of the original cohort) born in 1996-1997, with up to 14 stature measurements from birth to 7 years. Linear spline multi-level models with 3 knots at 3, 12 and 34 months were used to analyse birth length and growth velocity during four age-periods by parental educational achievement (up to secondary school, advanced secondary/partial university, completed university) and occupation (manual, non-manual).Girls born to the most (versus least) educated mothers were 0.43 cm (95% confidence interval (CI): 0.28, 0.58) longer at birth; for boys, the corresponding difference was 0.30 cm (95% CI: 0.15, 0.46). Similarly, children of the most educated mothers grew faster from birth-3 months and 12-34 months (p-values for trend ≤ 0.08), such that, by age 7 years, girls with the most (versus least) educated mothers were 1.92 cm (95% CI: 1.47, 2.36) taller; after controlling for urban/rural and East/West area of residence, this difference remained at 1.86 cm (95% CI: 1.42, 2.31), but after additionally controlling for mid-parental height, attenuated to 1.10 cm (95% CI: 0.69, 1.52). Among boys, these differences were 1.95 cm (95% CI: 1.53, 2.37), 1.89 cm (95% CI: 1.47, 2.31) and 1.16 cm (95% CI: 0.77, 1.55), respectively. Additionally controlling for breastfeeding, maternal smoking and older siblings did not substantively alter these findings. There was no evidence that the association of maternal educational attainment with growth differed in girls compared to boys (p for interaction = 0.45). Results were similar for those born to the most (versus least) educated fathers, or who had a parent with a non-manual (versus manual) occupation.In Belarus, a middle-income former Soviet country, socioeconomic differences in offspring growth commence in the pre-natal period and generate up to approximately 2 cm difference in height at age 7 years. These associations are partly explained by genetic or other factors influencing parental stature.Current Controlled Trials: NCT01352247 assigned 9 Sept 2005; ClinicalTrials.gov. Identifier: NCT01561612 received 20 Mar 2012.Rita Patel, Kate Tilling, Debbie A Lawlor, Laura D Howe, Natalia Bogdanovich, Lidia Matush, Emily Nicoli, Michael S Kramer and Richard M Marti

    A cluster randomised controlled trial of the Wellbeing in Secondary Education (WISE) Project – an intervention to improve the mental health support and training available to secondary school teachers: protocol for an integrated process evaluation

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    This is the author accepted manuscript. The final version is available from BioMed Central via the DOI in this record.Background Secondary school teachers have low levels of wellbeing and high levels of depression compared with the general population. Teachers are in a key position to support students, but poor mental health may be a barrier to doing so effectively. The Wellbeing in Secondary Education (WISE) project is a cluster randomised controlled trial (RCT) of an intervention to improve the mental health support and training available to secondary school teachers through delivery of the training package Mental Health First Aid and a staff peer support service. We will conduct a process evaluation as part of the WISE trial to support the interpretation of trial outcomes and refine intervention theory. The domains assessed will be: the extent to which the hypothesised mechanisms of change are activated; system level influences on these mechanisms; programme differentiation and usual practice; intervention implementation, including any adaptations; intervention acceptability; and intervention sustainability. Methods Research questions will be addressed via quantitative and qualitative methods. All study schools (n = 25) will provide process evaluation data, with more detailed focus group, interview and observation data being collected from a subsample of case study schools (4 intervention and 4 control). Mechanisms of change, as outlined in a logic model, will be measured via teacher and student surveys and focus groups. School context will be explored via audits of school practice that relate to mental health and wellbeing, combined with stakeholder interviews and focus groups. Implementation of the training and peer support service will be assessed via training observations, training participant evaluation forms, focus groups with participants, interviews with trainers and peer support service users, and peer supporter logs recording help provided. Acceptability and sustainability will be examined via interviews with funders, head teachers, trainers and peer support services users, and focus groups with training participants. Discussion The process evaluation embedded within the WISE cluster RCT will illuminate how and why the intervention was effective, ineffective or conferred iatrogenic effects. It will contribute to the refinement of the theory underpinning the intervention, and will help to inform any future implementation. Trial registration International Standard Randomised Controlled Trial Number: ISRCTN95909211 registered on 24 March 2016.The work was undertaken with the support of The Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer), a UKCRC Public Health Research Centre of Excellence. Joint funding (MR/KO232331/1) from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the Welsh Government and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. The authors acknowledge the contribution of the WISE Study research administrators Amy Bond and Odell Harris

    Inter-comparison of snow depth over Arctic sea ice from reanalysis reconstructions and satellite retrieval

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    In this study, we compare eight recently developed snow depth products over Arctic sea ice, which use satellite observations, modeling, or a combination of satellite and modeling approaches. These products are further compared against various ground-truth observations, including those from ice mass balance observations and airborne measurements. Large mean snow depth discrepancies are observed over the Atlantic and Canadian Arctic sectors. The differences between climatology and the snow products early in winter could be in part a result of the delaying in Arctic ice formation that reduces early snow accumulation, leading to shallower snowpacks at the start of the freeze-up season. These differences persist through spring despite overall more winter snow accumulation in the reanalysis-based products than in the climatologies. Among the products evaluated, the University of Washington (UW) snow depth product produces the deepest spring (March-April) snowpacks, while the snow product from the Danish Meteorological Institute (DMI) provides the shallowest spring snow depths. Most snow products show significant correlation with snow depths retrieved from Operational IceBridge (OIB) while correlations are quite low against buoy measurements, with no correlation and very low variability from University of Bremen and DMI products. Inconsistencies in reconstructed snow depth among the products, as well as differences between these products and in situ and airborne observations, can be partially attributed to differences in effective footprint and spatial-temporal coverage, as well as insufficient observations for validation/bias adjustments. Our results highlight the need for more targeted Arctic surveys over different spatial and temporal scales to allow for a more systematic comparison and fusion of airborne, in situ and remote sensing observations
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