Changes in Waist Circumference and the Incidence of Acute Myocardial Infarction in Middle-Aged Men and Women

BACKGROUND: Waist circumference (WC) measured at one point in time is positively associated with the risk of acute myocardial infarction (MI), but the association with changes in WC (DWC) is not clear. We investigated the association between DWC and the risk of MI in middle-aged men and women, and evaluated the influence from concurrent changes in BMI (DBMI). METHODOLOGY/PRINCIPAL FINDINGS: Data on 38,593 participants from the Danish Diet, Cancer and Health study was analysed. Anthropometry was assessed in 1993-97 and 1999-02. Information on fatal and non-fatal MI was obtained from National Registers. Cases were validated by review of the medical records. Hazard ratios (HR) were calculated from Cox proportional hazard models with individuals considered at risk from 1999-02 until December 30 2009. During 8.4 years of follow-up, 1,041 incident cases of MI occurred. WC was positively associated with the risk of MI, but weakly after adjustment for BMI. DWC was not associated with the risk of MI (HR per 5 cm change = 1.01 (0.95, 1.09) with adjustment for covariates, baseline WC, BMI and DBMI). Associations with DWC were not notably different in sub-groups stratified according to baseline WC or DBMI, or when individuals with MI occurring within the first years of follow-up were excluded. CONCLUSIONS/SIGNIFICANCE: WC was positively associated with the risk of MI in middle-aged men and women, but changes in WC were not. These findings suggest that a reduction in WC may be an insufficient target for prevention of MI in middle-aged men and women

Immune-related genetic enrichment in frontotemporal dementia: An analysis of genome-wide association studies

Background: Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. Methods and findings: Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders\u2014namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)\u2014and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis. We found up to 270-fold genetic enrichment between FTD and RA, up to 160-fold genetic enrichment between FTD and UC, up to 180-fold genetic enrichment between FTD and T1D, and up to 175-fold genetic enrichment between FTD and CeD. In contrast, for CBD and PSP, only 1 of the 6 immune-mediated diseases produced genetic enrichment comparable to that seen for FTD, with up to 150-fold genetic enrichment between CBD and CeD and up to 180-fold enrichment between PSP and RA. Further, we found minimal enrichment between ALS and the immune-mediated diseases tested, with the highest levels of enrichment between ALS and RA (up to 20-fold). For FTD, at a conjunction false discovery rate < 0.05 and after excluding SNPs in linkage disequilibrium, we found that 8 of the 15 identified loci mapped to the human leukocyte antigen (HLA) region on Chromosome (Chr) 6. We also found novel candidate FTD susceptibility loci within LRRK2 (leucine rich repeat kinase 2), TBKBP1 (TBK1 binding protein 1), and PGBD5 (piggyBac transposable element derived 5). Functionally, we found that the expression of FTD\u2013immune pleiotropic genes (particularly within the HLA region) is altered in postmortem brain tissue from patients with FTD and is enriched in microglia/macrophages compared to other central nervous system cell types. The main study limitation is that the results represent only clinically diagnosed individuals. Also, given the complex interconnectedness of the HLA region, we were not able to define the specific gene or genes on Chr 6 responsible for our pleiotropic signal. Conclusions: We show immune-mediated genetic enrichment specifically in FTD, particularly within the HLA region. Our genetic results suggest that for a subset of patients, immune dysfunction may contribute to FTD risk. These findings have potential implications for clinical trials targeting immune dysfunction in patients with FTD

Koulutusluokitus : Koulutuskoodimuutokset vuonna 1989, Liite 3

A measurement of inclusive ZZ production cross section and constraints on anomalous triple gauge couplings in proton-proton collisions at $\sqrt{s}$ = 8 TeV are presented. A data sample, corresponding to an integrated luminosity of 19.6 inverse-femtobarns was collected with the CMS experiment at the LHC. The measurements are performed in the leptonic decay modes $ZZ \to lll'l'$, where $l = e, \mu$ and $l' = e, \mu, \tau$. The measured total cross section, $\sigma (pp \to ZZ) = 7.7 \pm 0.5 (stat.)^{+0.5}_{-0.4} (syst.) \pm 0.4 (theo.) \pm 0.2 (lum.) pb$ for both Z bosons produced in the mass range $m_Z$ within 60 and 120 GeV, is consistent with standard model predictions. Differential cross sections are measured and well described by the theoretical predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ$\gamma$ couplings at the 95% confidence level: $f_4^Z$ in (-0.004,+0.004), $f_5^Z$ in (-0.005,+0.005), $f_4^\gamma$ in (-0.004,+0.004), and $f_5^\gamma$ in (-0.005,+0.005)

Measurement of the ratio B(t -> Wb)/B(t -> Wq) in pp collisions at root s=8 TeV

The ratio of the top-quark branching fractions R = B(t --> Wb)/B(t --> Wq), where the denominator includes the sum over all down-type quarks (q = b, s, d), is measured in the t (t) over bar dilepton final state with proton-proton collision data at root s = 8 TeV from an integrated luminosity of 19.7 fb(-1), collected with the CMS detector. In order to quantify the purity of the signal sample, the cross section is measured by fitting the observed jet multiplicity, thereby constraining the signal and background contributions. By counting the number of b jets per event, an unconstrained value of R = 1.014 +/- 0.003 (stat.) +/- 0.032 (syst.) is measured, in a good agreement with current precision measurements in electroweak and flavour sectors. A lower limit R > 0.955 at the 95% confidence level is obtained after requiring R 0.975 is set at 95% confidence level. The result is combined with a previous CMS measurement of the t-channel single-top-quark cross section to determine the top-quark total decay width, Gamma(t) = 1.36 +/- 0.02 (stat.)(-0.11)(+0.14) (syst.) GeV