Cardiovascular Risk Factors and Dehydroepiandrosterone Sulfate Among Latinos in the Boston Puerto Rican Health Study.

Low blood dehydroepiandrosterone sulfate (DHEAS) levels have strong positive associations with stroke and coronary heart disease. However, it is unclear whether DHEAS is independently associated with cardiovascular risk factors. Therefore, we examined the association between cardiovascular risk factors and DHEAS concentration among a high-risk population of Latinos (Puerto Ricans aged 45 to 75 years at baseline) in a cross-sectional analysis of the Boston Puerto Rican Health Study. Of eligible participants, 72% completed baseline interviews and provided blood samples. Complete data were available for 1355 participants. Associations between cardiovascular risk factors (age, sex, total cholesterol, high-density lipid cholesterol, triglycerides, and glucose) and log-transformed DHEAS (μg/dL) were assessed. In robust multivariable regression analyses, DHEAS was significantly inversely associated with age (β = -12.4; 95% CI: -15.2, -9.7; per 5 years), being female (vs. male) (β = -46; 95% CI: -55.3, -36.6), and plasma triglyceride concentration (β = -0.2; 95% CI: -0.3, -0.1; per 10 mg/dL) and was positively associated with total cholesterol and plasma glucose levels (β = 1.8; 95% CI: 0.6, 3 and β = 0.2; 95% CI: 0.04, 0.3, respectively, per 10 mg/dL) after adjustment for smoking, alcohol, and physical activity and for postmenopausal hormone use in women. Estimates were unchanged after adjustment for measures of chronic disease and inflammation. Women exhibited a stronger age-related decline in DHEAS and a positive association with glucose in contrast to findings among men (P interaction < 0.05). In conclusion, in this large study of Latinos with a heavy cardiovascular risk factor burden, we observed significant associations between cardiovascular disease (CVD) risk factors and DHEAS, with variations by sex. These findings improve our understanding of the role DHEAS may play in CVD etiology

Genome-Wide Association with Diabetes-Related Traits in the Framingham Heart Study

BACKGROUND: Susceptibility to type 2 diabetes may be conferred by genetic variants having modest effects on risk. Genome-wide fixed marker arrays offer a novel approach to detect these variants. METHODS: We used the Affymetrix 100K SNP array in 1,087 Framingham Offspring Study family members to examine genetic associations with three diabetes-related quantitative glucose traits (fasting plasma glucose (FPG), hemoglobin A1c, 28-yr time-averaged FPG (tFPG)), three insulin traits (fasting insulin, HOMA-insulin resistance, and 0–120 min insulin sensitivity index); and with risk for diabetes. We used additive generalized estimating equations (GEE) and family-based association test (FBAT) models to test associations of SNP genotypes with sex-age-age2-adjusted residual trait values, and Cox survival models to test incident diabetes. RESULTS: We found 415 SNPs associated (at p 1%) 100K SNPs in LD (r2 > 0.05) with ABCC8 A1369S (rs757110), KCNJ11 E23K (rs5219), or SNPs in CAPN10 or HNFa. PPARG P12A (rs1801282) was not significantly associated with diabetes or related traits. CONCLUSION: Framingham 100K SNP data is a resource for association tests of known and novel genes with diabetes and related traits posted at. Framingham 100K data replicate the TCF7L2 association with diabetes.National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1); National Center for Research Resources General Clinical Research Center (M01-RR-01066); American Diabetes Association Career Developement Award; GlaxoSmithKline; Merck; Lilly; National Institutes of Health Research Career Award (K23 DK659678-03

Implementation and performance of SIBYLS: a dual endstation small-angle X-ray scattering and macromolecular crystallography beamline at the Advanced Light Source.

The SIBYLS beamline (12.3.1) of the Advanced Light Source at Lawrence Berkeley National Laboratory, supported by the US Department of Energy and the National Institutes of Health, is optimized for both small-angle X-ray scattering (SAXS) and macromolecular crystallography (MX), making it unique among the world's mostly SAXS or MX dedicated beamlines. Since SIBYLS was commissioned, assessments of the limitations and advantages of a combined SAXS and MX beamline have suggested new strategies for integration and optimal data collection methods and have led to additional hardware and software enhancements. Features described include a dual mode monochromator [containing both Si(111) crystals and Mo/B(4)C multilayer elements], rapid beamline optics conversion between SAXS and MX modes, active beam stabilization, sample-loading robotics, and mail-in and remote data collection. These features allow users to gain valuable insights from both dynamic solution scattering and high-resolution atomic diffraction experiments performed at a single synchrotron beamline. Key practical issues considered for data collection and analysis include radiation damage, structural ensembles, alternative conformers and flexibility. SIBYLS develops and applies efficient combined MX and SAXS methods that deliver high-impact results by providing robust cost-effective routes to connect structures to biology and by performing experiments that aid beamline designs for next generation light sources

Do insect outbreaks reduce the severity of subsequent forest fires?

Understanding the causes and consequences of rapid environmental change is an essential scientific frontier, particularly given the threat of climate- and land use-induced changes in disturbance regimes. In western North America, recent widespread insect outbreaks and wildfires have sparked acute concerns about potential insect-fire interactions. Although previous research shows that insect activity typically does not increase wildfire likelihood, key uncertainties remain regarding insect effects on wildfire severity (i.e., ecological impact). Recent assessments indicate that outbreak severity and burn severity are not strongly associated, but these studies have been limited to specific insect or fire events. Here, we present a regional census of large wildfire severity following outbreaks of two prevalent bark beetle and defoliator species, mountain pine beetle (Dendroctonus ponderosae) and western spruce budworm (Choristoneura freemani), across the US Pacific Northwest. We first quantify insect effects on burn severity with spatial modeling at the fire event scale and then evaluate how these effects vary across the full population of insect-fire events (n = 81 spanning 1987-2011). In contrast to common assumptions of positive feedbacks, we find that insects generally reduce the severity of subsequent wildfires. Specific effects vary with insect type and timing, but both insects decrease the abundance of live vegetation susceptible to wildfire at multiple time lags. By dampening subsequent burn severity, native insects could buffer rather than exacerbate fire regime changes expected due to land use and climate change. In light of these findings, we recommend a precautionary approach when designing and implementing forest management policies intended to reduce wildfire hazard and increase resilience to global change

Tracer Tests in a Fractured Dolomite: 2. Controls on Mass-Recovery Rates for a Single-Porosity, Heterogeneous Conceptualization

A single-well injection-withdrawal (SWIW) test is evaluated as a tool to differentiate between single- and double-porosity conceptualizations of a system. Results from single-porosity simulations incorporating plume drift are also compared to observed data from a recent series of SWIW tests conducted in a fractured dolomite unit, for which a double-porosity conceptualization has been proposed. We evaluate the difficulty of differentiating the response for a double-porosity conceptualization from that for a heterogeneous, single-porosity conceptualization incorporating plume drift. Results of sensitivity studies on multiple, stochastically generated, heterogeneous transmissivity fields indicate that to simulate extremely slow mass-recovery rates for a SWIW test with a single-porosity conceptualization, the following conditions must be present: plume drift, extreme heterogeneities (high {sigma}InT), and an unusual configuration of the high and low transmissivity regions relative to the well location. A compilation of existing data suggests that the high degree of heterogeneity necessary is rare at the SWIW test scale.The observed data from the SWIW tracer tests cannot be matched to numerical simulation results when a single-porosity conceptualization is assumed. A signature of significant drift is less than 100% mass recovery with a zero derivative with respect to time of the late-time normalized cumulative mass curve indicating mass transported outside the capture zone of the withdrawal well. To minimize the risk of misinterpretation, an important design feature for SWIW tests is the collection of late-time data so that percent total mass recovery can be calculated

Rationale for the H-19 and H-11 tracer tests at the WIPP site

The Waste Isolation Pilot Plant (WIPP) is a repository for transuranic wastes constructed in bedded Permian-age halite in the Delaware Basin, a sedimentary basin in southeastern New Mexico, USA. A drilling scenario has been identified during performance assessment (PA) that could lead to the release of radionuclides to the Culebra Dolomite Member of the Rustler Formation, the most transmissive water-saturated unit above the repository horizon. Were this to occur, the radionuclides would need to be largely contained within the Culebra (or neighboring strata) within the WIPP-site boundary through the period lasting for 10,000 years after repository closure for WIPP to remain in compliance with applicable regulations on allowable releases. Thus, processes affecting transport of radionuclides within the Culebra are of importance to PA

Genome-Wide Association with Select Biomarker Traits in the Framingham Heart Study

BACKGROUND: Systemic biomarkers provide insights into disease pathogenesis, diagnosis, and risk stratification. Many systemic biomarker concentrations are heritable phenotypes. Genome-wide association studies (GWAS) provide mechanisms to investigate the genetic contributions to biomarker variability unconstrained by current knowledge of physiological relations. METHODS: We examined the association of Affymetrix 100K GeneChip single nucleotide polymorphisms (SNPs) to 22 systemic biomarker concentrations in 4 biological domains: inflammation/oxidative stress; natriuretic peptides; liver function; and vitamins. Related members of the Framingham Offspring cohort (n = 1012; mean age 59 ± 10 years, 51% women) had both phenotype and genotype data (minimum-maximum per phenotype n = 507–1008). We used Generalized Estimating Equations (GEE), Family Based Association Tests (FBAT) and variance components linkage to relate SNPs to multivariable-adjusted biomarker residuals. Autosomal SNPs (n = 70,987) meeting the following criteria were studied: minor allele frequency ≥ 10%, call rate ≥ 80% and Hardy-Weinberg equilibrium p ≥ 0.001. RESULTS: With GEE, 58 SNPs had p < 10-6: the top SNPs were rs2494250 (p = 1.00*10-14) and rs4128725 (p = 3.68*10-12) for monocyte chemoattractant protein-1 (MCP1), and rs2794520 (p = 2.83*10-8) and rs2808629 (p = 3.19*10-8) for C-reactive protein (CRP) averaged from 3 examinations (over about 20 years). With FBAT, 11 SNPs had p < 10-6: the top SNPs were the same for MCP1 (rs4128725, p = 3.28*10-8, and rs2494250, p = 3.55*10-8), and also included B-type natriuretic peptide (rs437021, p = 1.01*10-6) and Vitamin K percent undercarboxylated osteocalcin (rs2052028, p = 1.07*10-6). The peak LOD (logarithm of the odds) scores were for MCP1 (4.38, chromosome 1) and CRP (3.28, chromosome 1; previously described) concentrations; of note the 1.5 support interval included the MCP1 and CRP SNPs reported above (GEE model). Previous candidate SNP associations with circulating CRP concentrations were replicated at p < 0.05; the SNPs rs2794520 and rs2808629 are in linkage disequilibrium with previously reported SNPs. GEE, FBAT and linkage results are posted at . CONCLUSION: The Framingham GWAS represents a resource to describe potentially novel genetic influences on systemic biomarker variability. The newly described associations will need to be replicated in other studies.National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC25195); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1); National Institutes of Health (HL064753, HL076784, AG028321, HL71039, 2 K24HL04334, 1K23 HL083102); Doris Duke Charitable Foundation; American Diabetes Association Career Developement Award; National Center for Research Resources (GCRC M01-RR01066); US Department of Agriculture Agricultural Research Service (58-1950-001, 58-1950-401); National Institute of Aging (AG14759

Effect of Aging on A1C Levels in Individuals Without Diabetes: Evidence from the Framingham Offspring Study and the National Health and Nutrition Examination Survey 2001–2004

OBJECTIVE—Although glycemic levels are known to rise with normal aging, the nondiabetic A1C range is not age specific. We examined whether A1C was associated with age in nondiabetic subjects and in subjects with normal glucose tolerance (NGT) in two population-based cohorts

Association Between Parental History of Type 2 Diabetes and Glycemic Control in Urban African Americans

OBJECTIVE—The purpose of this study was to examine the association between parental history of type 2 diabetes and glycemic control among diabetic urban African Americans