The PPARγ2 P12A polymorphism is not associated with all-cause mortality in patients with type 2 diabetes mellitus

The high mortality risk of patients with type 2 diabetes mellitus may well be explained by the several comorbidities and/or complications. Also the intrinsic genetic component predisposing to diabetes might have a role in shaping the risk of diabetes-related mortality. Among type 2 diabetes mellitus SNPs, rs1801282 is of particular interest because (i) it is harbored by peroxisome proliferator-activated receptor-γ2 (PPARγ2), which is the target for thiazolidinediones which are used as antidiabetic drugs, decreasing all-cause mortality in type 2 diabetes mellitus, and (ii) it is associated with insulin resistance and related traits, risk factors for overall mortality in type 2 diabetes mellitus. We investigated the role of PPARγ2 P12A, according to a dominant model (PA + AA vs. PP individuals) on incident all-cause mortality in three cohorts of type 2 diabetes mellitus, comprising a total of 1672 patients (462 deaths) and then performed a meta-analysis of ours and all available published data. In the three cohorts pooled and analyzed together, no association between PPARγ2 P12A and all-cause mortality was observed (HR 1.02, 95 % CI 0.79–1.33). Similar results were observed after adjusting for age, sex, smoking habits, and BMI (HR 1.09, 95 % CI 0.83–1.43). In a meta-analysis of ours and all studies previously published (n = 3241 individuals; 666 events), no association was observed between PPARγ2 P12A and all-cause mortality (HR 1.07, 95 % CI 0.85–1.33). Results from our individual samples as well as from our meta-analysis suggest that the PPARγ2 P12A does not significantly affect all-cause mortality in patients with type 2 diabetes mellitus

Circulating adiponectin and cardiovascular mortality in patients with type 2 diabetes mellitus: evidence of sexual dimorphism

Background: The pathogenesis of cardiovascular (CV) mortality, whose rate is increased in type 2 diabetes, is poorly understood. While high serum adiponectin is associated with increased CV mortality in the general population, no data are available in type 2 diabetes. We here investigated whether this counterintuitive association was observable also in diabetic patients and whether it was sex-specific. Methods: Three prospective cohorts were analyzed: 1) Gargano Heart Study (GHS; 359 patients, 58 events/1,934 person-years; py); 2) Health Professional Follow-up Study (HPFS; 833 men, 146 events/10,024 py); 3) Nurses’ Health Study (NHS; 902 women, 144 events/15,074 py). Results: In GHS serum adiponectin predicted CV mortality in men (hazard ratio, HR, and 95% CI per standard deviation, SD, increment = 1.54, 1.19-2.01), but not women (HR = 0.98, 0.48-2.01). Circulating adiponectin predicted CV mortality in men from HPFS (HR = 1.44, 1.21-1.72), but not in women from NHS (HR = 1.08, 0.86-1.35), used as replication samples. In a pooled analysis, HRs were 1.47 (1.27-1.70) in 1,075 men and 1.07 (0.86-1.33) in 1,019 women (p for HRs heterogeneity across sexes = 0.018). Conclusions: This is the first report showing that high circulating adiponectin predicts increased CV mortality in men, but not in women with type 2 diabetes. Further studies are necessary to unravel the mechanisms through which adiponectin influences CV mortality in a sex-specific manner. Electronic supplementary material The online version of this article (doi:10.1186/s12933-014-0130-y) contains supplementary material, which is available to authorized users

Serum Resistin, Cardiovascular Disease and All-Cause Mortality in Patients with Type 2 Diabetes

Background: High serum resistin has been associated with increased risk of cardiovascular disease in the general population, Only sparse and conflicting results, limited to Asian individuals, have been reported, so far, in type 2 diabetes. We studied the role of serum resistin on coronary artery disease, major cardiovascular events and all-cause mortality in type 2 diabetes. Methods: We tested the association of circulating resistin concentrations with coronary artery disease, major cardiovascular events (cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) and all-cause mortality in 2,313 diabetic patients of European ancestry from two cross-sectional and two prospective studies. In addition, the expression of resistin gene (RETN) was measured in blood cells of 68 diabetic patients and correlated with their serum resistin levels. Results: In a model comprising age, sex, smoking habits, BMI, HbA1c, and insulin, antihypertensive and antidyslipidemic therapies, serum resistin was associated with coronary artery disease in both cross-sectional studies: OR (95%CI) per SD increment = 1.35 (1.10–1.64) and 1.99 (1.55–2.55). Additionally, serum resistin predicted incident major cardiovascular events (HR per SD increment = 1.31; 1.10–1.56) and all-cause mortality (HR per SD increment = 1.16; 1.06–1.26). Adjusting also for fibrinogen levels affected the association with coronary artery disease and incident cardiovascular events, but not that with all cause-mortality. Finally, serum resistin was positively correlated with RETN mRNA expression (rho = 0.343). Conclusions: This is the first study showing that high serum resistin (a likely consequence, at least partly, of increased RETN expression) is a risk factor for cardiovascular disease and all-cause mortality in diabetic patients of European ancestry

The ENPP1 Q121 Variant Predicts Major Cardiovascular Events in High-Risk Individuals: Evidence for Interaction With Obesity in Diabetic Patients

Insulin resistance (IR) and cardiovascular disease may share a common genetic background. We investigated the role of IR-associated ENPP1 K121Q polymorphism (rs1044498) on cardiovascular disease in high-risk individuals

Measurement of the CP-violating phase ϕs and the Bs0 meson decay width difference with Bs0 → J/ψϕ decays in ATLAS

A measurement of the Bs0 decay parameters in the Bs0 → J/ψϕ channel using an integrated luminosity of 14.3 fb−1 collected by the ATLAS detector from 8 TeV pp collisions at the LHC is presented. The measured parameters include the CP -violating phase ϕs, the decay width Γs and the width difference between the mass eigenstates ΔΓs. The values measured for the physical parameters are statistically combined with those from 4.9 fb−1 of 7 TeV data, leading to the following: ϕ s =−0.090±0.078(stat.)±0.041(syst.)rad ΔΓ s =0.085±0.011(stat.)±0.007(syst.)ps −1 Γ s =0.675±0.003(stat.)±0.003(syst.)ps −1 In the analysis the parameter ΔΓs is constrained to be positive. Results for ϕs and ΔΓs are also presented as 68% and 95% likelihood contours in the ϕs-ΔΓs plane. Also measured in this decay channel are the transversity amplitudes and corresponding strong phases. All measurements are in agreement with the Standard Model predictions

Search for massive, long-lived particles using multitrack displaced vertices or displaced lepton pairs in pp collisions at √s = 8 TeV with the ATLAS detector

Many extensions of the Standard Model posit the existence of heavy particles with long lifetimes. This article presents the results of a search for events containing at least one long-lived particle that decays at a significant distance from its production point into two leptons or into five or more charged particles. This analysis uses a data sample of proton-proton collisions at √s=8  TeV corresponding to an integrated luminosity of 20.3  fb−1 collected in 2012 by the ATLAS detector operating at the Large Hadron Collider. No events are observed in any of the signal regions, and limits are set on model parameters within supersymmetric scenarios involving R-parity violation, split supersymmetry, and gauge mediation. In some of the search channels, the trigger and search strategy are based only on the decay products of individual long-lived particles, irrespective of the rest of the event. In these cases, the provided limits can easily be reinterpreted in different scenarios

Measurement of the production cross-section of a single top quark in association with a W boson at 8 TeV with the ATLAS experiment

The cross-section for the production of a single top quark in association with a W boson in proton-proton collisions at s√=8TeV is measured. The dataset corresponds to an integrated luminosity of 20.3 fb−1, collected by the ATLAS detector in 2012 at the Large Hadron Collider at CERN. Events containing two leptons and one central b-jet are selected. The W t signal is separated from the backgrounds using boosted decision trees, each of which combines a number of discriminating variables into one classifier. Production of W t events is observed with a significance of 7.7σ. The cross-section is extracted in a profile likelihood fit to the classifier output distributions. The W t cross-section, inclusive of decay modes, is measured to be 23.0 ± 1.3(stat.)− 3.5+ 3.2(syst.)±1.1(lumi.) pb. The measured cross-section is used to extract a value for the CKM matrix element |Vtb| of 1.01 ± 0.10 and a lower limit of 0.80 at the 95% confidence level. The cross-section for the production of a top quark and a W boson is also measured in a fiducial acceptance requiring two leptons with pT> 25 GeV and |η| 20 GeV and |η|  20 GeV, including both W t and top-quark pair events as signal. The measured value of the fiducial cross-section is 0.85 ± 0.01(stat.)− 0.07+ 0.07(syst.)±0.03(lumi.) pb

Measurement of the differential cross-section of highly boosted top quarks as a function of their transverse momentum in s =8 TeV proton-proton collisions using the ATLAS detector

The differential cross-section for pair production of top quarks with high transverse momentum is measured in 20.3  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The measurement is performed for tt¯ events in the lepton+jets channel. The cross-section is reported as a function of the hadronically decaying top quark transverse momentum for values above 300 GeV. The hadronically decaying top quark is reconstructed as an anti-kt jet with radius parameter R=1.0 and identified with jet substructure techniques. The observed yield is corrected for detector effects to obtain a cross-section at particle level in a fiducial region close to the event selection. A parton-level cross-section extrapolated to the full phase space is also reported for top quarks with transverse momentum above 300 GeV. The predictions of a majority of next-to-leading-order and leading-order matrix-element Monte Carlo generators are found to agree with the measured cross-sections.- We thank CERN for the very successful operation of the LHC, as well as the support staff from our institutions without whom ATLAS could not be operated efficiently. We acknowledge the support of ANPCyT, Argentina; YerPhI, Armenia; ARC, Australia; BMWFW and FWF, Austria; ANAS, Azerbaijan; SSTC, Belarus; CNPq and FAPESP, Brazil; NSERC, NRC and CFI, Canada; CERN; CONICYT, Chile; CAS, MOST and NSFC, China; COLCIENCIAS, Colombia; MSMT CR, MPO CR and VSC CR, Czech Republic; DNRF, DNSRC and Lundbeck Foundation, Denmark; IN2P3-CNRS, CEA-DSM/IRFU, France; GNSF, Georgia; BMBF, HGF, and MPG, Germany; GSRT, Greece; RGC, Hong Kong SAR, China; ISF, I-CORE and Benoziyo Center, Israel; INFN, Italy; MEXT and JSPS, Japan; CNRST, Morocco; FOM and NWO, Netherlands; RCN, Norway; MNiSW and NCN, Poland; FCT, Portugal; MNE/IFA, Romania; MES of Russia and NRC KI, Russian Federation; JINR; MESTD, Serbia; MSSR, Slovakia; ARRS and MIZS, Slovenia; DST/NRF, South Africa; MINECO, Spain; SRC and Wallenberg Foundation, Sweden; SERI, SNSF and Cantons of Bern and Geneva, Switzerland; MOST, Taiwan; TAEK, Turkey; STFC, United Kingdom; DOE and NSF, United States of America. In addition, individual groups and members have received support from BCKDF, the Canada Council, CANARIE, CRC, Compute Canada, FQRNT, and the Ontario Innovation Trust, Canada; EPLANET, ERC, FP7, Horizon 2020 and Marie Sklodowska-Curie Actions, European Union; Investissements d'Avenir Labex and Idex, ANR, Region Auvergne and Fondation Partager le Savoir, France; DFG and AvH Foundation, Germany; Herakleitos, Thales and Aristeia programmes co-financed by EU-ESF and the Greek NSRF; BSF, GIF and Minerva, Israel; BRF, Norway; the Royal Society and Leverhulme Trust, United Kingdom. The crucial computing support from all WLCG partners is acknowledged gratefully, in particular from CERN and the ATLAS Tier-1 facilities at TRIUMF (Canada), NDGF (Denmark, Norway, Sweden), CC-IN2P3 (France), KIT/GridKA (Germany), INFN-CNAF (Italy), NL-T1 (Netherlands), PIC (Spain), ASGC (Taiwan), RAL (UK) an