748 research outputs found
Multiyear trends in volatile organic compounds in Los Angeles, California: Five decades of decreasing emissions
Basic and clinical immunology – 3028. Interaction of DNA methylation and genetic variants of IL13 is associated with FEV1/FVC and BHR
A Taxonomy of Fallacies in System Safety Arguments
Safety cases are gaining acceptance as assurance vehicles for safety-related systems. A safety case documents the evidence and argument that a system is safe to operate; however, logical fallacies in the underlying argument may undermine a system s safety claims. Removing these fallacies is essential to reduce the risk of safety-related system failure. We present a taxonomy of common fallacies in safety arguments that is intended to assist safety professionals in avoiding and detecting fallacious reasoning in the arguments they develop and review. The taxonomy derives from a survey of general argument fallacies and a separate survey of fallacies in real-world safety arguments. Our taxonomy is specific to safety argumentation, and it is targeted at professionals who work with safety arguments but may lack formal training in logic or argumentation. We discuss the rationale for the selection and categorization of fallacies in the taxonomy. In addition to its applications to the development and review of safety cases, our taxonomy could also support the analysis of system failures and promote the development of more robust safety case patterns
"Driven to distraction?" Children's experiences of car travel
This is an Author's Accepted Manuscript of an article published in volume, 4, issue 1, pages 59-76 in Mobilities 2009. Copyright @ 2009 Taylor & Francis, available online at: http://www.tandfonline.com/doi/abs/10.1080/17450100802657962.Cars have become increasingly significant features in the lives of many children and adults in the UK and elsewhere. Whilst there is a growing body of research considering how adults experience automobility, that is the increasingly central role of cars within societies, there has been little equivalent research exploring children's perspectives. Drawing upon a variety of methods including personal diaries, photographs, in‐depth interviews and surveys amongst schools within Buckinghamshire and North London, the paper contributes to filling this gap in existing research through exploring how cars are not only journey spaces for children, but are also sites for play, relaxation, homework, companionship, technology and the consumption of commodities. Using a Foucauldian analysis of power, insights into wider familial processes relating to mobility are provided by exploring how cars are sites of conflicting power relations between parents and children. The paper also explores how children's everyday experiences of cars were framed by wider sets of power relations, including car corporations which design and manufacture these spaces, and the role of capital which commodifies everyday activities in cars. In doing so, the paper challenges existing research on automobility for only focusing upon adults' experiences of cars and begins to theorise a more inclusive account of automobility which incorporates children and young people
Gambling Harm as a Global Public Health Concern: A Mixed Method Investigation of Trends in Wales
Background: Recent research evidence has suggested that gambling is a public health concern. A number of studies report the association between gambling activity and increased instances of various other harms, including substance misuse and psychological disorders. In parallel to alcohol misuse, it is also becoming clear that gambling related harm is more of a continuum of harm, as opposed to traditionally accepted categorisations of gambling behavior: safe and responsible or “problem” and harmful. Previous effective treatment models for alcohol misuse have considered a public health approach to develop interventions. As such, the current research seeks to use a public health approach to both investigate the extent of gambling harm across Wales, and to identify upstream predictors of harm to inform future interventions. /
Method: A triangulation of data collection methods was utilized across Wales, UK. Two hundred and forty-eight participants completed a quantitative survey relating to gambling behavior and related harm, which included the Problem Severity Gambling Index, the Gambling Commission measure of frequency, The Gambling Motives Questionnaire and the Fast Alcohol Screening tool. Ninety-eight of these participants completed a qualitative subsection. Structured interviews were conducted with 20 individuals from 11 service providers. Semi-structured interviews were conducted for the five case studies of individuals who had previously sought help for gambling. The geographical density and distribution of Licensed Gambling Outlets was also mapped in local areas. /
Results: The findings provide further evidence of a continuum of gambling related harm. Twenty seven percent of survey participants demonstrate some indicators of risk of gambling harm. Social, cultural and environmental contexts play a role in initiation and maintenance of gambling behavior and the subsequent related harm. Accounts from individuals corroborated the quantitative findings. /
Conclusions: Findings from this Welsh sample are in line with and add support to the growing international research evidence that gambling harms are a universal issue that cross cultures. It is clear that action is needed by legislators at a policy level and that broadening the focus of intervention to a public health level is necessary to develop effective strategies for harm reduction
Evaluating the efficacy of breastfeeding guidelines on long-term outcomes for allergic disease
Background: WHO guidelines advocate breastfeeding for six months, and EAACI recommends exclusive breastfeeding for 4-6 months. However, evidence for breastfeeding to prevent asthma and allergic disease is conflicting. We examined whether following recommended breastfeeding guidelines alters the long-term risks of asthma, eczema, rhinitis, or atopy.Methods: The effect of non-exclusive (0, >0-6, >6 months), and exclusive breastfeeding (0, >0-4, >4 months) on repeated measures of asthma (10, 18 years), eczema, rhinitis, and atopy (1-or-2, 4, 10,18 years) risks were estimated in the IoW cohort (n=1456) using log-linear models with generalised estimating equations. The Food Allergy and Intolerance Research (FAIR) cohort (n=988), also from the IoW, was examined to replicate results.Results: Breastfeeding (any or exclusive) had no effect on asthma and allergic disease in the IoW cohort. In the FAIR cohort, any breastfeeding for >0-6 months protected against asthma at 10 years (RR=0.50, 95%CI=0.32-0.79, p=0.003) but not other outcomes, while exclusive breastfeeding for >4 months protected against repeated rhinitis (RR=0.36, 95%CI=0.18-0.71, p=0.003). Longer breastfeeding was protective against late-onset wheeze in the IoW cohort.Conclusion: The protective effects of non-exclusive and exclusive breastfeeding against long-term allergic outcomes were inconsistent between these co-located cohorts, agreeing with previous observations of heterogeneous effects. Although breastfeeding should be recommended for other health benefits, following breastfeeding guidelines did not appear to afford consistent protection against long-term asthma, eczema, rhinitis or atopy. Further research is needed into the long-term effects of breastfeeding on allergic disease
Development of childhood asthma prediction models using machine learning approaches
Background: Respiratory symptoms are common in early life and often transient. It is difficult to identify in which children these will persist and result in asthma. Machine learning (ML) approaches have the potential for better predictive performance and generalisability over existing childhood asthma prediction models. This study applied ML approaches to predict school-age asthma (age 10) in early life (Childhood Asthma Prediction in Early life, CAPE model) and at preschool age (Childhood Asthma Prediction at Preschool age, CAPP model). Methods: Clinical and environmental exposure data was collected from children enrolled in the Isle of Wight Birth Cohort (N = 1368, ∼15% asthma prevalence). Recursive Feature Elimination (RFE) identified an optimal subset of features predictive of school-age asthma for each model. Seven state-of-the-art ML classification algorithms were used to develop prognostic models. Training was performed by applying fivefold cross-validation, imputation, and resampling. Predictive performance was evaluated on the test set. Models were further externally validated in the Manchester Asthma and Allergy Study (MAAS) cohort. Results: RFE identified eight and twelve predictors for the CAPE and CAPP models, respectively. Support Vector Machine (SVM) algorithms provided the best performance for both the CAPE (area under the receiver operating characteristic curve, AUC = 0.71) and CAPP (AUC = 0.82) models. Both models demonstrated good generalisability in MAAS (CAPE 8-year = 0.71, 11-year = 0.71, CAPP 8-year = 0.83, 11-year = 0.79) and excellent sensitivity to predict a subgroup of persistent wheezers. Conclusion: Using ML approaches improved upon the predictive performance of existing regression-based models, with good generalisability and ability to rule in asthma and predict persistent wheeze.</p
Changes in DNA methylation from pre- to post-adolescence are associated with pubertal exposures
Background
Adolescence is a period characterized by major biological development, which may be associated with changes in DNA methylation (DNA-M). However, it is unknown to what extent DNA-M varies from pre- to post-adolescence, whether the pattern of changes is different between females and males, and how adolescence-related factors are associated with changes in DNA-M.
Methods
Genome-scale DNA-M at ages 10 and 18 years in whole blood of 325 subjects (n = 140 females) in the Isle of Wight (IOW) birth cohort was analyzed using Illumina Infinium arrays (450K and EPIC). Linear mixed models were used to examine DNA-M changes between pre- and post-adolescence and whether the changes were gender-specific. Adolescence-related factors and environmental exposure factors were assessed on their association with DNA-M changes. Replication of findings was attempted in the comparable Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.
Results
In the IOW cohort, after controlling for technical variation and cell compositions at both pre- and post-adolescence, 15,532 cytosine–phosphate–guanine (CpG) sites (of 400,825 CpGs, 3.88%) showed statistically significant DNA-M changes from pre-adolescence to post-adolescence invariant to gender (false discovery rate (FDR) = 0.05). Of these 15,532 CpGs, 10,212 CpGs (66%) were replicated in the ALSPAC cohort. Pathway analysis using Ingenuity Pathway Analysis (IPA) identified significant biological pathways related to growth and development of the reproductive system, emphasizing the importance of this period of transition on epigenetic state of genes. In addition, in IOW, we identified 1179 CpGs with gender-specific DNA-M changes. In the IOW cohort, body mass index (BMI) at age 10 years, age of growth spurt, nonsteroidal drugs use, and current smoking status showed statistically significant associations with DNA-M changes at 15 CpGs on 14 genes such as the AHRR gene. For BMI at age 10 years, the association was gender-specific. Findings on current smoking status were replicated in the ALSPAC cohort.
Conclusion
Adolescent transition is associated with changes in DNA-M at more than 15K CpGs. Identified pathways emphasize the importance of this period of transition on epigenetic state of genes relevant to cell growth and immune system development
Modeling Wheezing Spells Identifies Phenotypes with Different Outcomes and Genetic Associates
Funding Information: Supported by the UK Medical Research Council (UK MRC) Programme grant MR/S025340/1 and grants G0601361 and MR/K002449/1. R.G. is in part funded through Wellcome Trust Strategic Award 108818/15/Z. The UK MRC and Wellcome (grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC (Avon Longitudinal Study of Parents and Children). MAAS (Manchester Asthma and Allergy Study) was supported by the Asthma UK Grants No 301 (1995–1998), No 362 (1998–2001), No 01/012 (2001–2004), No 04/014 (2004–2007), British Medical Association James Trust (2005), and the JP Moulton Charitable Foundation (2004–2016), the North West Lung Centre Charity (1997–current), and the UK MRC grant MR/L012693/1 (2014–2018). Acknowledgment This article is dedicated to the memory of our wonderful colleague and friend Prof. John Henderson (1958–2019), whose contribution to the understanding of the heterogeneity of childhood asthma cannot be overstated. Rainbow chasers and UNICORN riders forever.Peer reviewedPublisher PD
The interplay of DNA methylation over time with Th2 pathway genetic variants on asthma risk and temporal asthma transition
BackgroundGenetic effects on asthma of genes in the T-helper 2 (Th2) pathway may interact with epigenetic factors including DNA methylation. We hypothesized that interactions between genetic variants and methylation in genes in this pathway (IL4, IL4R, IL13, GATA3, and STAT6) influence asthma risk, that such influences are age-dependent, and that methylation of some CpG sites changes over time in accordance with asthma transition. We tested these hypotheses in subsamples of girls from a population-based birth cohort established on the Isle of Wight, UK, in 1989.ResultsLogistic regression models were applied to test the interaction effect of DNA methylation and SNP on asthma within each of the five genes. Bootstrapping was used to assess the models identified. From 1,361 models fitted at each age of 10 and 18 years, 8 models, including 4 CpGs and 8 SNPs, showed potential associations with asthma risk. Of the 4 CpGs, methylation of cg26937798 (IL4R) and cg23943829 (IL4) changes between ages 10 and 18 (both higher at 10; P?=?9.14?×?10?6 and 1.07?×?10?5, respectively).At age 10, the odds of asthma tended to decrease as cg12405139 (GATA3) methylation increased (log-OR?=??12.15; P?=?0.049); this effect disappeared by age 18. At age 18, methylation of cg09791102 (IL4R) was associated with higher risk of asthma among subjects with genotype GG compared to AG (P?=?0.003), increased cg26937798 methylation among subjects with rs3024685 (IL4R) genotype AA (P?=?0.003) or rs8832 (IL4R) genotype GG (P?=?0.01) was associated with a lower asthma risk; these CpGs had no effect at age 10. Increasing cg26937798 methylation over time possibly reduced the risk of positive asthma transition (asthma-free at age 10???asthma at age 18; log-OR?=??3.11; P?=?0.069) and increased the likelihood of negative transition (asthma at age 10???asthma-free at age 18; log-OR?=?3.97; P?=?0.074).ConclusionsThe interaction of DNA methylation and SNPs in Th2 pathway genes is likely to contribute to asthma risk. This effect may vary with age. Methylation of some CpGs changed over time, which may influence asthma transition
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