Context Bisphenol A (BPA) is widely used in epoxy resins lining food and beverage containers. Evidence of effects in animals has generated concern over low-level chronic exposures in humans.Objective To examine associations between urinary BPA concentrations and adult health status.Design, Setting, and Participants Cross-sectional analysis of BPA concentrations and health status in the general adult population of the United States, using data from the National Health and Nutrition Examination Survey 2003-2004. Participants were 1455 adults aged 18 through 74 years with measured urinary BPA and urine creatinine concentrations. Regression models were adjusted for age, sex, race/ ethnicity, education, income, smoking, body mass index, waist circumference, and urinary creatinine concentration. The sample provided 80% power to detect unadjusted odds ratios (ORs) of 1.4 for diagnoses of 5% prevalence per 1-SD change in BPA concentration, or standardized regression coefficients of 0.075 for liver enzyme concentrations, at a significance level of PϽ.05. Main Outcome MeasuresChronic disease diagnoses plus blood markers of liver function, glucose homeostasis, inflammation, and lipid changes. ResultsHigher urinary BPA concentrations were associated with cardiovascular diagnoses in age-, sex-, and fully adjusted models (OR per 1-SD increase in BPA concentration, 1.39; 95% confidence interval [CI], 1.18-1.63; P=.001 with full adjustment). Higher BPA concentrations were also associated with diabetes (OR per 1-SD increase in BPA concentration, 1.39; 95% confidence interval [CI], 1.21-1.60; PϽ.001) but not with other studied common diseases. In addition, higher BPA concentrations were associated with clinically abnormal concentrations of the liver enzymes ␥-glutamyltransferase (OR per

Objective To determine whether, and to what extent, physical activity interventions affect the overall activity levels of children.Design Systematic review and meta-analysis.Data sources Electronic databases (Embase, Medline, PsycINFO, SPORTDiscus) and reference lists of included studies and of relevant review articles.Study selection Design: randomised controlled trials or controlled clinical trials (cluster and individual) published in peer reviewed journals. Intervention: incorporated a component designed to increase the physical activity of children/adolescents and was at least four weeks in duration. Outcomes: measured whole day physical activity objectively with accelerometers either before or immediately after the end of the intervention period. Data analysisIntervention effects (standardised mean differences) were calculated for total physical activity, time spent in moderate or vigorous physical activity, or both for each study and pooled using a weighted random effects model. Meta-regression explored the heterogeneity of intervention effects in relation to study participants, design, intervention type, and methodological quality.Results Thirty studies (involving 14 326 participants; 6153 with accelerometer measured physical activity) met the inclusion criteria and all were eligible for meta-analysis/meta-regression. The pooled intervention effect across all studies was small to negligible for total physical activity (standardised mean difference 0.12, 95% confidence interval 0.04 to 0.20; P<0.01) and small for moderate or vigorous activity (0.16, 0.08 to 0.24; P<0.001). Meta-regression indicated that the pooled intervention effect did not differ significantly between any of the subgroups (for example, for total physical activity, standardised mean differences were 0.07 for age <10 years and 0.16 for ≥10 years, P=0.19; 0.07 for body mass index across the entire range and 0.22 for exclusively overweight/obese children, P=0.07; 0.12 for study duration ≤6 months and 0.09 for >6 months, P=0.71; 0.15 for home/family based intervention and 0.10 for school based intervention, P=0.53; and 0.09 for higher quality studies and 0.14 for lower quality studies, P=0.52). ConclusionsThis review provides strong evidence that physical activity interventions have had only a small effect (approximately 4 minutes more walking or running per day) on children's overall activity levels. This finding may explain, in part, why such interventions have had limited success in reducing the body mass index or body fat of children. IntroductionPhysical activity is associated with many health benefits, 1-3 but most children fail to meet national recommendations. [4][5][6] Prevention of obesity in particular is thought to be one of the benefits to being more active, and accordingly most interventions aimed at reducing childhood obesity incorporate a physical activity component. Observational studies consistently show that greater activity is associated (r~−0.2) with lower body mass index and girth, 7-11 yet physical activity int...

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts – cis effects, and elsewhere in the genome – trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10−57), CCL4L1 (p = 3.9×10−21), IL18 (p = 6.8×10−13), LPA (p = 4.4×10−10), GGT1 (p = 1.5×10−7), SHBG (p = 3.1×10−7), CRP (p = 6.4×10−6) and IL1RN (p = 7.3×10−6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10−40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways.

Credit scoring is the term used to describe formal statistical methods used for classifying applicants for credit into`good' and`bad' risk classes. Such methods have become increasingly important with the dramatic growth in consumer credit in recent years. A wide range of statistical methods has been applied, though the literature available to the public is limited for reasons of commercial con®dentiality. Particular problems arising in the credit scoring context are examined and the statistical methods which have been applied are reviewed.