Globular cluster systems of spiral and S0 galaxies: Results from WIYN imaging of NGC1023, NGC1055, NGC7332, and NGC7339

We present results from a study of the globular cluster (GC) systems of four spiral and S0 galaxies imaged as part of an ongoing wide-field survey of the GC systems of giant galaxies. The target galaxies - the SB0 galaxy NGC1023, the SBb galaxy NGC1055, and an isolated pair comprised of the Sbc galaxy NGC7339 and the S0 galaxy NGC7332 - were observed in BVR filters with the WIYN 3.5m telescope and Minimosaic camera. For two of the galaxies, we combined the WIYN imaging with previously published data from the $\textit{Hubble Space Telescope}$ and the Keck Observatory to help characterize the GC distribution in the central few kiloparsecs. We determine the radial distribution (surface density of GCs versus projected radius) of each galaxy's GC system and use it to calculate the total number of GCs ($N_{GC}$). We find $N_{GC}$ = 490 ± 30, 210 ± 40, 175 ± 15, and 75 ± 10 for NGC1023, NGC1055, NGC7332, and NGC7339, respectively. We also calculate the GC specific frequency (N GC normalized by host galaxy luminosity or mass) and find values typical of those of the other spiral and E/S0 galaxies in the survey. The two lenticular galaxies have sufficient numbers of GC candidates for us to perform statistical tests for bimodality in the GC color distributions. We find evidence at a high confidence level (>95%) for two populations in the $B - R$ distribution of the GC system of NGC1023. We find weaker evidence for bimodality (>81% confidence) in the GC color distribution of NGC7332. Finally, we identify eight GC candidates that may be associated with the Magellanic dwarf galaxy NGC1023A, which is a satellite of NGC1023

Evidence for Association between SH2B1 Gene Variants and Glycated Hemoglobin in Nondiabetic European American Young Adults: The Add Health Study

Glycated hemoglobin (HbA1c) is used to classify glycaemia and type 2 diabetes (T2D). Body mass index (BMI) is a predictor of HbA1c levels and T2D. We tested 43 established BMI and obesity loci for association with HbA1c in a nationally representative multiethnic sample of young adults from the National Longitudinal Study of Adolescent to Adult Health [Add Health: age 24–34 years; n = 5641 European Americans (EA); 1740 African Americans (AA); 1444 Hispanic Americans (HA)] without T2D, using two levels of covariate adjustment (Model 1: age, sex, smoking, and geographic region; Model 2: Model 1 covariates plus BMI). Bonferroni adjustment was made for 43 SNPs and we considered P < 0.0011 statistically significant. Means (SD) for HbA1c were 5.4% (0.3) in EA, 5.7% (0.4) in AA, and 5.5% (0.3) in HA. We observed significant evidence for association with HbA1c for two variants near SH2B1 in EA (rs4788102, P = 2.2 × 10−4; rs7359397, P = 9.8 × 10−4) for Model 1. Both results were attenuated after adjustment for BMI (rs4788102, P = 1.7 × 10−3; rs7359397, P = 4.6 × 10−3). No variant reached Bonferroni-corrected significance in AA or HA. These results suggest that SH2B1 polymorphisms are associated with HbA1c, largely independent of BMI, in EA young adults

Comparison of case note review methods for evaluating quality and safety in health care

Objectives: To determine which of two methods of case note review – holistic (implicit) and criterion-based (explicit) – provides the most useful and reliable information for quality and safety of care, and the level of agreement within and between groups of health-care professionals when they use the two methods to review the same record. To explore the process–outcome relationship between holistic and criterion-based quality-of-care measures and hospital-level outcome indicators. © 2010 Crown Copyrigh

A Nearly Linear-Time PTAS for Explicit Fractional Packing and Covering Linear Programs

We give an approximation algorithm for packing and covering linear programs (linear programs with non-negative coefficients). Given a constraint matrix with n non-zeros, r rows, and c columns, the algorithm computes feasible primal and dual solutions whose costs are within a factor of 1+eps of the optimal cost in time O((r+c)log(n)/eps^2 + n).Comment: corrected version of FOCS 2007 paper: 10.1109/FOCS.2007.62. Accepted to Algorithmica, 201

Operator renewal theory and mixing rates for dynamical systems with infinite measure

We develop a theory of operator renewal sequences in the context of infinite ergodic theory. For large classes of dynamical systems preserving an infinite measure, we determine the asymptotic behaviour of iterates $L^n$ of the transfer operator. This was previously an intractable problem. Examples of systems covered by our results include (i) parabolic rational maps of the complex plane and (ii) (not necessarily Markovian) nonuniformly expanding interval maps with indifferent fixed points. In addition, we give a particularly simple proof of pointwise dual ergodicity (asymptotic behaviour of $\sum_{j=1}^nL^j$) for the class of systems under consideration. In certain situations, including Pomeau-Manneville intermittency maps, we obtain higher order expansions for $L^n$ and rates of mixing. Also, we obtain error estimates in the associated Dynkin-Lamperti arcsine laws.Comment: Preprint, August 2010. Revised August 2011. After publication, a minor error was pointed out by Kautzsch et al, arXiv:1404.5857. The updated version includes minor corrections in Sections 10 and 11, and corresponding modifications of certain statements in Section 1. All main results are unaffected. In particular, Sections 2-9 are unchanged from the published versio

Open chromatin profiling in adipose tissue marks genomic regions with functional roles in cardiometabolic traits

Identifying the regulatory mechanisms of genome-wide association study (GWAS) loci affecting adipose tissue has been restricted due to limited characterization of adipose transcriptional regulatory elements. We profiled chromatin accessibility in three frozen human subcutaneous adipose tissue needle biopsies and preadipocytes and adipocytes from the Simpson Golabi-Behmel Syndrome (SGBS) cell strain using an assay for transposase-accessible chromatin (ATAC-seq). We identified 68,571 representative accessible chromatin regions (peaks) across adipose tissue samples (FDR, 5%). GWAS loci for eight cardiometabolic traits were enriched in these peaks (P, 0.005), with the strongest enrichment for waist-hip ratio. Of 110 recently described cardiometabolic GWAS loci colocalized with adipose tissue eQTLs, 59 loci had one or more variants overlapping an adipose tissue peak. Annotated variants at the SNX10 waist-hip ratio locus and the ATP2A1-SH2B1 body mass index locus showed allelic differences in regulatory assays. These adipose tissue accessible chromatin regions elucidate genetic variants that may alter adipose tissue function to impact cardiometabolic traits

Development of innovative tools for investigation of nutrient-gut interaction

The gastrointestinal tract is the key interface between the ingesta and the human body. There is wide recognition that the gastrointestinal response to nutrients or bioactive compounds, particularly the secretion of numerous hormones, is critical to the regulation of appetite, body weight and blood glucose. This concept has led to an increasing focus on "gut-based" strategies for the management of metabolic disorders, including type 2 diabetes and obesity. Understanding the underlying mechanisms and downstream effects of nutrient-gut interactions is fundamental to effective translation of this knowledge to clinical practice. To this end, an array of research tools and platforms have been developed to better understand the mechanisms of gut hormone secretion from enteroendocrine cells. This review discusses the evolution of in vitro and in vivo models and the integration of innovative techniques that will ultimately enable the development of novel therapies for metabolic diseases.Wei-Kun Huang, Cong Xie, Richard L Young, Jiang-Bo Zhao, Heike Ebendorff-Heidepriem, Karen L Jones ... et al

Influence of alcohol consumption and alcohol metabolism variants on breast cancer risk among Black women: results from the AMBER consortium

Background: Moderate to heavy alcohol consumption is associated with an increased risk of breast cancer. The etiologic role of genetic variation in genes involved in ethanol metabolism has not been established, with little information available among women of African ancestry. Methods: Our analysis from the African American Breast Cancer Epidemiology and Risk (AMBER) Consortium included 2889 U.S. Black women who were current drinkers at the time of breast cancer diagnosis (N cases = 715) and had available genetic data for four ethanol metabolism genomic regions (ADH, ALDH, CYP2E1, and ALDH2). We used generalized estimating equations to calculate genetic effects, gene* alcohol consumption (≥ 7drinks/week vs. < 7/week) interactions, and joint main plus interaction effects of up to 23,247 variants in ethanol metabolism genomic regions on odds of breast cancer. Results: Among current drinkers, 21% of cases and 14% of controls reported consuming ≥ 7 drinks per week. We identified statistically significant genetic effects for rs79865122-C in CYP2E1 with odds of ER- breast cancer and odds of triple negative breast cancer, as well as a significant joint effect with odds of ER- breast cancer (≥ 7drinks per week OR = 3.92, < 7 drinks per week OR = 0.24, pjoint = 3.74 × 10−6). In addition, there was a statistically significant interaction of rs3858704-A in ALDH2 with consumption of ≥ 7 drinks/week on odds of triple negative breast cancer (≥ 7drinks per week OR = 4.41, < 7 drinks per week OR = 0.57, pint = 8.97 × 10–5). Conclusions: There is a paucity of information on the impact of genetic variation in alcohol metabolism genes on odds of breast cancer among Black women. Our analysis of variants in four genomic regions harboring ethanol metabolism genes in a large consortium of U.S. Black women identified significant associations between rs79865122-C in CYP2E1 and odds of ER- and triple negative breast cancer. Replication of these findings is warranted

Moderate to vigorous physical activity interactions with genetic variants and body mass index in a large US ethnically diverse cohort

Summary What is already known about this subject Genome-Wide Association Studies have successfully identified numerous genetic loci that influence body mass index in European-descent middle-aged adults. Adolescence is a high-risk period for the development of adult obesity and severe obesity. Physical activity is one of the most promising behavioural candidates for preventing and reducing weight gain, particularly among youth. What this study adds An examination of the joint association between 41 of the well-established obesity susceptibility single-nucleotide polymorphisms with <5 vs. ≥5 bouts of moderate to vigorous physical activity (MVPA) per week in relation to body mass index (BMI)-for-age Z-score in a nationally representative sample of European American, African-American and Hispanic American adolescents. Three nominally significant interactions (P < 0.05) varied by race/ethnicity. Overall, the estimated effect of the risk allele on BMI-for-age Z-score was greater in individuals with <5 than those with ≥5 bouts MVPA per week. Background Little is known about the interaction between genetic and behavioural factors during lifecycle risk periods for obesity and how associations vary across race/ethnicity. Objective The objective of this study was to examine joint associations of adiposity-related single-nucleotide polymorphisms (SNPs) and moderate to vigorous physical activity (MVPA) with body mass index (BMI) in a diverse adolescent cohort. Methods Using data from the National Longitudinal Study of Adolescent Health (n = 8113: Wave II 1996; ages 12-21, Wave III; ages 18-27), we assessed interactions of 41 well-established SNPs and MVPA with BMI-for-age Z-scores in European Americans (EA; n = 5077), African-Americans (AA; n = 1736) and Hispanic Americans (HA; n = 1300). Results Of 97 assessed, we found nominally significant SNP-MVPA interactions on BMI-for-age Z-score in EA at GNPDA2 and FTO and in HA at LZTR2/SEC16B. In EA, the estimated effect of the FTO risk allele on BMI-for-age Z-score was lower (β = -0.13; 95% confidence interval [CI]: 0.08, 0.18) in individuals with ≥5 vs. <5 (β = 0.24; CI: 0.16, 0.32) bouts of MVPA per week (P for interaction 0.02). Race/ethnicity-pooled meta-analysis showed nominally significant interactions for SNPs at TFAP2B, POC5 and LYPLAL1. Conclusions High MVPA may attenuate underlying genetic risk for obesity during adolescence, a high-risk period for adult obesity

Screen time behaviours may interact with obesity genes, independent of physical activity, to influence adolescent BMI in an ethnically diverse cohort

Background There has been little investigation of gene-by-environment interactions related to sedentary behaviour, a risk factor for obesity defined as leisure screen time (ST; i.e. television, video and computer games). Objective To test the hypothesis that limiting ST use attenuates the genetic predisposition to increased body mass index (BMI), independent of physical activity. Design Using 7642 wave II participants of the National Longitudinal Study of Adolescent Health, (Add Health; mean=16.4 years, 52.6% female), we assessed the interaction of ST (hweek-1) and 41 established obesity single nucleotide polymorphisms (SNPs) with age- and sex-specific BMI Z-scores in 4788 European-American (EA), 1612 African-American (AA) and 1242 Hispanic American (HA) adolescents. Results Nominally significant SNP ST interaction were found for FLJ35779 in EA, GNPDA2 in AA and none in HA (EA: beta [SE]=0.016[0.007]), AA: beta [SE]=0.016[0.011]) per 7hweek-1 ST and one risk allele in relation to BMI Z-score. Conclusions While for two established BMI loci, we find evidence that high levels of ST exacerbate the influence of obesity susceptibility variants on body mass; overall, we do not find strong evidence for interactions between the majority of established obesity loci. However, future studies with larger sample sizes, or that may build on our current study and the growing published literature, are clearly warranted