268 research outputs found

    A Population Pharmacokinetic Analysis Shows that Arylacetamide Deacetylase (AADAC) Gene Polymorphism and HIV Infection Affect the Exposure of Rifapentine.

    Get PDF
    Rifapentine is a rifamycin used to treat tuberculosis. As is the case for rifampin, plasma exposures of rifapentine are associated with the treatment response. While concomitant food intake and HIV infection explain part of the pharmacokinetic variability associated with rifapentine, few studies have evaluated the contribution of genetic polymorphisms. We evaluated the effects of functionally significant polymorphisms of the genes encoding OATP1B1, the pregnane X receptor (PXR), constitutive androstane (CAR), and arylacetamide deacetylase (AADAC) on rifapentine exposure. Two studies evaluating novel regimens among southern African patients with drug-susceptible pulmonary tuberculosis were included in this analysis. In the RIFAQUIN study, rifapentine was administered in the continuation phase of antituberculosis treatment in 1,200-mg-once-weekly or 900-mg-twice-weekly doses. In the Daily RPE study, 450 or 600 mg was given daily during the intensive phase of treatment. Nonlinear mixed-effects modeling was used to describe the pharmacokinetics of rifapentine and to identify significant covariates. A total of 1,144 drug concentration measurements from 326 patients were included in the analysis. Pharmacogenetic information was available for 162 patients. A one-compartment model with first-order elimination and transit compartment absorption described the data well. In a typical patient (body weight, 56 kg; fat-free mass, 45 kg), the values of clearance and volume of distribution were 1.33 liters/h and 25 liters, respectively. Patients carrying the AA variant (65.4%) of AADAC rs1803155 were found to have a 10.4% lower clearance. HIV-infected patients had a 21.9% lower bioavailability. Once-weekly doses of 1,200 mg were associated with a reduced clearance (13.2%) compared to that achieved with more frequently administered doses. Bioavailability was 23.3% lower among patients participating in the Daily RPE study than in those participating in the RIFAQUIN study. This is the first study to report the effect of AADAC rs1803155AA on rifapentine clearance. The observed increase in exposure is modest and unlikely to be of clinical relevance. The difference in bioavailability between the two studies is probably related to the differences in food intake concomitant with the dose. HIV-coinfected patients had lower rifapentine exposures

    Global baryon number conservation encoded in net-proton fluctuations measured in Pb–Pb collisions at √sNN = 2.76 TeV

    Get PDF
    Experimental results are presented on event-by-event net-proton fluctuation measurements in Pb–Pb collisions at √SNN=2.76 TeV, recorded by the ALICE detector at the CERN LHC. These measurements have as their ultimate goal an experimental test of Lattice QCD (LQCD) predictions on second and higher order cumulants of net-baryon distributions to search for critical behavior near the QCD phase boundary. Before confronting them with LQCD predictions, account has to be taken of correlations stemming from baryon number conservation as well as fluctuations of participating nucleons. Both effects influence the experimental measurements and are usually not considered in theoretical calculations. For the first time, it is shown that event-by-event baryon number conservation leads to subtle long-range correlations arising from very early interactions in the collisions.publishedVersio

    Search for the production of dark matter in association with top-quark pairs in the single-lepton final state in proton-proton collisions at √s=8 TeV

    Get PDF
    Peer reviewe

    Search for disappearing tracks in proton-proton collisions at √s=8 TeV

    Get PDF
    Peer reviewe

    Search for vector-like T quarks decaying to top quarks and Higgs bosons in the all-hadronic channel using jet substructure

    Get PDF
    Peer reviewe

    Precise determination of the mass of the Higgs boson and tests of compatibility of its couplings with the standard model predictions using proton collisions at 7 and 8 TeV

    Get PDF
    Peer reviewe

    Searches for supersymmetry using the M-T2 variable in hadronic events produced in pp collisions at 8 TeV

    Get PDF
    Peer reviewe

    Search for physics beyond the standard model in dilepton mass spectra in proton-proton collisions at √s=8 TeV

    Get PDF
    Peer reviewe

    Study of final-state radiation in decays of Z bosons produced in pp collisions at 7 TeV

    Get PDF
    The differential cross sections for the production of photons in Z→Ό+ÎŒ-Îł decays are presented as a function of the transverse energy of the photon and its separation from the nearest muon. The data for these measurements are collected with the CMS detector and correspond to an integrated luminosity of 4.7fb-1 of pp collisions at s=7TeV delivered by the CERN LHC. The cross sections are compared to simulations with powheg and pythia, where pythia is used to simulate parton showers and final-state photons. These simulations match the data to better than 5%

    Search for standard model production of four top quarks in the lepton + jets channel in pp collisions at √s = 8 TeV

    Get PDF
    Open Access, Copyright CERN, for the benefit of the CMS Collaboration. Article funded by SCOAP3.Abstract: A search is presented for standard model (SM) production of four top quarks (Formula presented.) in pp collisions in the lepton + jets channel. The data correspond to an integrated luminosity of 19.6 fb−1 recorded at a centre-of-mass energy of 8 TeV with the CMS detector at the CERN LHC. The expected cross section for SM (Formula presented.) production is (Formula presented.). A combination of kinematic reconstruction and multivariate techniques is used to distinguish between the small signal and large background. The data are consistent with expectations of the SM, and an upper limit of 32 fb is set at a 95% confidence level on the cross section for producing four top quarks in the SM, where a limit of 32 ± 17 fb is expected
    • 

    corecore