133 research outputs found

    Effectiveness of All-Oral Antiviral Regimens in 996 Human Immunodeficiency Virus/Hepatitis C Virus Genotype 1–Coinfected Patients Treated in Routine Practice

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    Background.Large cohorts are needed to assess human immunodeficiency virus (HIV)/hepatitis C virus (HCV) real-world treatment outcomes. We examined the effectiveness of ledipasvir/sofosbuvir with or without ribavirin (LDV/SOF ± RBV) and ombitasvir/ paritaprevir/ritonavir plus dasabuvir (OPrD) ± RBV in HIV/HCV genotype 1 (GT1)-coinfected patients initiating HCV therapy in clinical practice.Methods.Observational intent-to-treat cohort analysis using the Veterans Affairs Clinical Case Registry to identify HIV/HCV GT1-coinfected veterans initiating 12 weeks of LDV/SOF ± RBV or OPrD ± RBV. Multivariate models of sustained virologic response (SVR) included age, race, cirrhosis, proton pump inhibitor (PPI) prescription, prior HCV treatment, body mass index, genotype subtype, and HCV treatment regimen.Results.Nine hundred ninety-six HIV/HCV GT1-coinfected veterans initiated therapy: 757 LDV/SOF, 138 LDV/SOF + RBV, 28 OPrD, and 73 OPrD + RBV. Overall SVR was 90.9% (823/905); LDV/SOF 92.1% (631/685), LDV/SOF + RBV 86.3% (113/131), OPrD 88.9% (24/27), and OPrD + RBV 88.7% (55/62). SVR was 85.9% (176/205) and 92.4% (647/700) in those with and without cirrhosis (P = .006). SVR was similar between African Americans (90.5% [546/603]) and all others (91.7% [277/302]). PPI use with LDV/SOF ± RBV did not affect SVR (89.7% [131/146] with PPI and 91.5% [613/670] without PPI). Cirrhosis was predictive of reduced SVR (0.51 [95% confidence interval {CI}, .31-.87]; P = .01). Median creatinine change did not differ among patients receiving LDV/SOF and tenofovir disoproxil fumarate (TDF) without a protease inhibitor (PI) (0.18 [interquartile range {IQR}, 0.08-0.30]; n = 372), LDV/SOF and TDF/PI (0.17 [IQR, 0.04-0.30]; n = 100), and LDV/SOF without TDF (0.15 [IQR, 0.00-0.30]; n = 423).Conclusions.SVR rates in HIV/HCV GT1-coinfected patients were high. African American race or PPI use with LDV/SOF ± RBV was not associated with lower SVR rates, but cirrhosis was. Renal function did not worsen on LDV/SOF regimens with TDF

    Observation of associated near-side and away-side long-range correlations in √sNN=5.02  TeV proton-lead collisions with the ATLAS detector

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    Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  Όb-1 of data as a function of transverse momentum (pT) and the transverse energy (ÎŁETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∌0) correlation that grows rapidly with increasing ÎŁETPb. A long-range “away-side” (Δϕ∌π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ÎŁETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ÎŁETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁥2Δϕ modulation for all ÎŁETPb ranges and particle pT

    Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

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    The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

    Morphological study of the antennal sensilla in Gerromorpha (Insecta: Hemiptera: Heteroptera)

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    The external morphology and distribution of the antennal sensilla of 21 species from five families of semiaquatic bugs (Gerromorpha) were examined using scanning electron microscopy. Nine main types were distinguished based on their morphological structure: sensilla trichoidea, sensilla chaetica, sensilla leaflike, sensilla campaniformia, sensilla coeloconica, sensilla ampullacea, sensilla basiconica, sensilla placoidea and sensilla bell-mouthed. The specific morphological structure of one type of sensilla (bell-mouthed sensilla) was observed only in Aquarius paludum. Several subtypes of sensilla are described, differentiated by number, location and type of sensillum characteristic for each examined taxon. The present study provides new data about the morphology and distribution of the antennal sensilla in Gerromorpha

    The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53- Independent Manner in Colon and Breast Cancer Cells

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    The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR) as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNα treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner, inducing phosphorylation of the protein synthesis translation initiation factor eIF-2α and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNα combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug

    Search for direct top squark pair production in events with a Z boson, b-jets and missing transverse momentum in s √ = 8 TeV pp collisions with the ATLAS detector

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    A search is presented for direct top squark pair production using events with at least two leptons including a same-flavour opposite-sign pair with invariant mass consistent with the Z boson mass, jets tagged as originating from b-quarks and missing transverse momentum. The analysis is performed with proton–proton collision data at s√=8 TeV collected with the ATLAS detector at the LHC in 2012 corresponding to an integrated luminosity of 20.3 fb−Âč. No excess beyond the Standard Model expectation is observed. Interpretations of the results are provided in models based on the direct pair production of the heavier top squark state (t~2) followed by the decay to the lighter top squark state (t~1) via t~2→Zt~1, and for t~1 pair production in natural gauge-mediated supersymmetry breaking scenarios where the neutralino (χ~10) is the next-to-lightest supersymmetric particle and decays producing a Z boson and a gravitino (G~) via the χ~10→ZG~ process

    Measurement of the ttÂŻ production cross-section using eÎŒ events with b-tagged jets in pp collisions at √s=7 and 8 TeV with the ATLAS detector

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    The inclusive top quark pair (ttÂŻ) production cross-section σttÂŻ has been measured in proton–proton collisions at √s=7 TeV and √s=8 TeV with the ATLAS experiment at the LHC, using ttÂŻ events with an opposite-charge eÎŒ pair in the final state. The measurement was performed with the 2011 7 TeV dataset corresponding to an integrated luminosity of 4.6 fb−1 and the 2012 8 TeV dataset of 20.3 fb−1. The numbers of events with exactly one and exactly two b-tagged jets were counted and used to simultaneously determine σttÂŻ and the efficiency to reconstruct and b-tag a jet from a top quark decay, thereby minimising the associated systematic uncertainties. The cross-section was measured to be: σttÂŻ=182.9±3.1±4.2±3.6±3.3 pb (s=7 TeV)and σttÂŻ=242.4±1.7±5.5±7.5±4.2 pb (s=8 TeV), where the four uncertainties arise from data statistics, experimental and theoretical systematic effects, knowledge of the integrated luminosity and of the LHC beam energy. The results are consistent with recent theoretical QCD calculations at next-to-next-to-leading order. Fiducial measurements corresponding to the experimental acceptance of the leptons are also reported, together with the ratio of cross-sections measured at the two centre-of-mass energies. The inclusive cross-section results were used to determine the top quark pole mass via the dependence of the theoretically predicted cross-section on mtpole giving a result of mtpole=172.9−2.6+2.5 GeV. By looking for an excess of ttÂŻ production with respect to the QCD prediction, the results were also used to place limits on the pair-production of supersymmetric top squarks t~1 with masses close to the top quark mass, decaying via t~1→tχ~10 to predominantly right-handed top quarks and a light neutralino χ~10, the lightest supersymmetric particle. Top squarks with masses between the top quark mass and 177 GeV are excluded at the 95 % confidence level
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