Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Vitamin C in plasma is inversely related to blood pressure and change in blood pressure during the previous year in young Black and White women

BackgroundThe prevalence of hypertension and its contribution to cardiovascular disease risk makes it imperative to identify factors that may help prevent this disorder. Extensive biological and biochemical data suggest that plasma ascorbic acid may be such a factor. In this study we examined the association between plasma ascorbic acid concentration and blood pressure (BP) in young-adult women.MethodsParticipants were 242 Black and White women aged 18-21 yr from the Richmond, CA, cohort of the National Heart, Lung and Blood Institute Growth and Health Study. We examined the associations of plasma ascorbic acid with BP at follow-up year 10, and with change in BP during the previous year.ResultsIn cross-sectional analysis, plasma ascorbic acid at year 10 was inversely associated with systolic BP and diastolic BP after adjusting for race, body mass index, education, and dietary intake of fat and sodium. Persons in the highest one-fourth of the plasma ascorbic acid distribution had 4.66 mmHg lower systolic BP (95% CI 1.10 to 8.22 mmHg, p = 0.005) and 6.04 mmHg lower diastolic BP (95% CI 2.70 to 9.38 mmHg, p = 0.0002) than those in the lowest one-fourth of the distribution. In analysis of the change in BP, plasma ascorbic acid was also inversely associated with change in systolic BP and diastolic BP during the previous year. While diastolic blood pressure among persons in the lowest quartile of plasma ascorbic acid increased by 5.97 mmHg (95% CI 3.82 to 8.13 mmHg) from year 9 to year 10, those in the highest quartile of plasma vitamin C increased by only 0.23 mmHg (95% CI -1.90 to +2.36 mmHg) (test for linear trend: p < 0.0001). A similar effect was seen for change in systolic BP, p = 0.005.ConclusionPlasma ascorbic acid was found to be inversely associated with BP and change in BP during the prior year. The findings suggest the possibility that vitamin C may influence BP in healthy young adults. Since lower BP in young adulthood may lead to lower BP and decreased incidence of age-associated vascular events in older adults, further investigation of treatment effects of vitamin C on BP regulation in young adults is warranted

Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization.

BACKGROUND: Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways. METHODS: To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses. RESULTS: Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology. CONCLUSIONS: Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.</p

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

The incidence and prevalence of heart failure (HF) and chronic kidney disease (CKD) are increasing, and as such a better understanding of the interface between both conditions is imperative for developing optimal strategies for their detection, prevention, diagnosis, and management. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened an international, multidisciplinary Controversies Conference titled Heart Failure in CKD. Breakout group discussions included (i) HF with preserved ejection fraction (HFpEF) and nondialysis CKD, (ii) HF with reduced ejection fraction (HFrEF) and nondialysis CKD, (iii) HFpEF and dialysis-dependent CKD, (iv) HFrEF and dialysis-dependent CKD, and (v) HF in kidney transplant patients. The questions that formed the basis of discussions are available on the KDIGO website http://kdigo.org/conferences/heart-failure-in-ckd/, and the deliberations from the conference are summarized her