23 research outputs found

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

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    Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

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    This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

    Measurement of D+- and D0 production in deep inelastic scattering using a lifetime tag at HERA

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    The production of D-+/-- and D-0-mesons has been measured with the ZEUS detector at HERA using an integrated luminosity of 133.6 pb(-1). The measurements cover the kinematic range 5 < Q(2) < 1000 GeV2, 0.02 < y < 0.7, 1.5 < p(T)(D) < 15 GeV and |eta(D)| < 1.6. Combinatorial background to the D-meson signals is reduced by using the ZEUS microvertex detector to reconstruct displaced secondary vertices. Production cross sections are compared with the predictions of next-to-leading-order QCD, which is found to describe the data well. Measurements are extrapolated to the full kinematic phase space in order to obtain the open-charm contribution, F-2(c (c) over bar), to the proton structure function, F-2

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

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    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

    Appropriateness of antiplatelet therapy for primary and secondary cardio- and cerebrovascular prevention in acutely hospitalized older people

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    Aims: Antiplatelet therapy is recommended for the secondary prevention of cardio- and cerebrovascular disease, but for primary prevention it is advised only in patients at very high risk. With this background, this study aims to assess the appropriateness of antiplatelet therapy in acutely hospitalized older people according to their risk profile. Methods: Data were obtained from the REPOSI register held in Italian and Spanish internal medicine and geriatric wards in 2012 and 2014. Hospitalized patients aged 6565 assessable at discharge were selected. Appropriateness of the antiplatelet therapy was evaluated according to their primary or secondary cardiovascular prevention profiles. Results: Of 2535 enrolled patients, 2199 were assessable at discharge. Overall 959 (43.6%, 95% CI 41.5\u201345.7) were prescribed an antiplatelet drug, aspirin being the most frequently chosen. Among patients prescribed for primary prevention, just over half were inappropriately prescribed (52.1%), being mainly overprescribed (155/209 patients, 74.2%). On the other hand, there was also a high rate of inappropriate underprescription in the context of secondary prevention (222/726 patients, 30.6%, 95% CI 27.3\u201334.0%). Conclusions: This study carried out in acutely hospitalized older people shows a high degree of inappropriate prescription among patients prescribed with antiplatelets for primary prevention, mainly due to overprescription. Further, a large proportion of patients who had had overt cardio- or cerebrovascular disease were underprescribed, in spite of the established benefits of antiplatelet drugs in the context of secondary prevention

    Production of Excited Charm and Charm-Strange Mesons at HERA

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    The production of excited charm, D 1(2420)0 and D 2 * (2460)0, and charm-strange, D s1(2536)±, mesons in ep collisions was measured with the ZEUS detector at HERA using an integrated luminosity of 126 pb -1. Masses, widths and helicity parameters were determined. The measured yields were converted to the rates of c quarks hadronising as a given excited charm meson and to the ratios of the dominant D 2 * (2460)0 and D s1(2536) ± branching fractions. A search for the radially excited charm meson, D *(2640)±, was also performed. The results are compared with those measured previously and with theoretical expectations

    BEAM TESTS OF THE ZEUS BARREL CALORIMETER

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    A fully compensating uranium-scintillator calorimeter was constructed for the ZEUS detector at HERA. Several of the barrel calorimeter modules were subjected to beam tests at Fermilab before shipping them to DESY for installation. The calibrations of the modules used beams of electrons and hadrons, measuring the uniformity of the response, and checking the resolution. The runs also provided opportunity to test a large fraction of the actual ZEUS calorimeter readout system in an integrated beam environment more than one year before HERA turn on. The experiment utilized two computer controlled mechanical structures. one of which was capable of holding up to four modules in order to study shower containment, and a magnetic spectrometer with a high resolution beam tracking system. During two running periods, beams of 6 to 110 GeV containing e, mu, pi, and pBAR were used. The results show energy resolutions of 35%/square-root E for hadrons and 19%/square-root E for electrons, uniformities at the 1% level, energy nonlinearity less than 1%, and equal response for electrons and hadrons

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

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    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

    Koulutusluokitus : Koulutuskoodimuutokset vuonna 1989, Liite 3

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    A measurement of inclusive ZZ production cross section and constraints on anomalous triple gauge couplings in proton-proton collisions at s\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 ZZllllZZ \to lll'l', where l=e,μl = e, \mu and l=e,μ,τl' = e, \mu, \tau. The measured total cross section, σ(ppZZ)=7.7±0.5(stat.)0.4+0.5(syst.)±0.4(theo.)±0.2(lum.)pb\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 mZm_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 ZZγ\gamma couplings at the 95% confidence level: f4Zf_4^Z in (-0.004,+0.004), f5Zf_5^Z in (-0.005,+0.005), f4γf_4^\gamma in (-0.004,+0.004), and f5γf_5^\gamma in (-0.005,+0.005)

    Constraints on the Higgs boson width from off-shell production and decay to Z-boson pairs

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    Constraints are presented on the total width of the recently discovered Higgs boson, Gamma(H), using its relative on-shell and off-shell production and decay rates to a pair of Z bosons, where one Z boson decays to an electron or muon pair, and the other to an electron, muon, or neutrino pair. The analysis is based on the data collected by the CMS experiment at the LHC in 2011 and 2012, corresponding to integrated luminosities of 5.1 fb(-1) at a center-of-mass energy root s = 7 TeV and 19.7 fb(-1) at root s = 8 TeV. A simultaneous maximum likelihood fit to the measured kinematic distributions near the resonance peak and above the Z-boson pair production threshold leads to an upper limit on the Higgs boson width of Gamma(H) < 22 MeV at a 95% confidence level, which is 5.4 times the expected value in the standard model at the measured mass of m(H) = 125.6 GeV
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