198 research outputs found
The beneficial effects of TAVI in mitral insufficiency.
Background Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization. Methods This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion, pleural effusion needing drainage, and renal insufficiency events (estimated glomerular filtration rate ≤30/mL/min per 1.73 m2) in de novo HTx recipients receiving immediate everolimus (EVR-I) (≤144 hours post-HTx) or delayed everolimus (EVR-D) (4-6 weeks post-HTx with mycophenolate mofetil as a bridge) with reduced-dose cyclosporine A. Cumulative incidence of biopsy-proven rejection ≥ 2R, rejection with hemodynamic compromise, graft loss, or death was the secondary composite efficacy endpoint. Results Overall, 181 patients were randomized to the EVR-I (n = 89) or EVR-D (n = 92) arms. Incidence of primary safety endpoint was higher for EVR-I than EVR-D arm (44.9% vs 32.6%; P = 0.191), mainly driven by a higher rate of pericardial effusion (33.7% vs 19.6%; P = 0.04); wound healing delays, acute renal insufficiency events, and pleural effusion occurred at similar frequencies in the study arms. Efficacy failure was not significantly different in EVR-I arm versus EVR-D arm (37.1% vs 28.3%; P = 0.191). Three patients in the EVR-I arm and 1 in the EVR-D arm died. Incidence of clinically significant adverse events leading to discontinuation was higher in EVR-I arm versus EVR-D arm (P = 0.02). Conclusions Compared with immediate initiation, delayed everolimus initiation appeared to provide a clinically relevant early safety benefit in de novo HTx recipients, without compromising efficacy. © 2017 The Author(s). Published by Wolters Kluwer Health, Inc
Measurement of the W+W-gamma Cross Section and Direct Limits on Anomalous Quartic Gauge Boson Couplings at LEP
The process e+e- -> W+W-gamma is analysed using the data collected with the
L3 detector at LEP at a centre-of-mass energy of 188.6GeV, corresponding to an
integrated luminosity of 176.8pb^-1. Based on a sample of 42 selected W+W-
candidates containing an isolated hard photon, the W+W-gamma cross section,
defined within phase-space cuts, is measured to be: sigma_WWgamma = 290 +/- 80
+/- 16 fb, consistent with the Standard Model expectation. Including the
process e+e- -> nu nu gamma gamma, limits are derived on anomalous
contributions to the Standard Model quartic vertices W+W- gamma gamma and W+W-Z
gamma at 95% CL: -0.043 GeV^-2 < a_0/Lambda^2 < 0.043 GeV^-2 0.08 GeV^-2 <
a_c/Lambda^2 < 0.13 GeV^-2 0.41 GeV^-2 < a_n/Lambda^2 < 0.37 GeV^-2
Production of Single W Bosons at \sqrt{s}=189 GeV and Measurement of WWgamma Gauge Couplings
Single W boson production in electron-positron collisions is studied with the
L3 detector at LEP. The data sample collected at a centre-of-mass energy of
\sqrt{s} = 188.7GeV corresponds to an integrated luminosity of 176.4pb^-1.
Events with a single energetic lepton or two acoplanar hadronic jets are
selected. Within phase-space cuts, the total cross-section is measured to be
0.53 +/- 0.12 +/- 0.03 pb, consistent with the Standard Model expectation.
Including our single W boson results obtained at lower \sqrt{s}, the WWgamma
gauge couplings kappa_gamma and lambda_gamma are determined to be kappa_gamma =
0.93 +/- 0.16 +/- 0.09 and lambda_gamma = -0.31 +0.68 -0.19 +/- 0.13
Measurement of Bose-Einstein Correlations in e+e- -> W+W- at root(s)=189GeV
We investigate Bose-Einstein correlations (BEC) in W-pair production at
root(s)=189GeV using the L3 detector at LEP. We observe BEC between particles
from a single W decay in good agreement with those from a light-quark Z decay
sample. We investigate their possible existence between particles coming from
different W's. No evidence for such inter-W BEC is found
The instrument suite of the European Spallation Source
An overview is provided of the 15 neutron beam instruments making up the initial instrument suite of the
European Spallation Source (ESS), and being made available to the neutron user community. The ESS neutron
source consists of a high-power accelerator and target station, providing a unique long-pulse time structure
of slow neutrons. The design considerations behind the time structure, moderator geometry and instrument
layout are presented.
The 15-instrument suite consists of two small-angle instruments, two reflectometers, an imaging beamline,
two single-crystal diffractometers; one for macromolecular crystallography and one for magnetism, two powder
diffractometers, and an engineering diffractometer, as well as an array of five inelastic instruments comprising
two chopper spectrometers, an inverse-geometry single-crystal excitations spectrometer, an instrument for vibrational
spectroscopy and a high-resolution backscattering spectrometer. The conceptual design, performance
and scientific drivers of each of these instruments are described.
All of the instruments are designed to provide breakthrough new scientific capability, not currently
available at existing facilities, building on the inherent strengths of the ESS long-pulse neutron source of high
flux, flexible resolution and large bandwidth. Each of them is predicted to provide world-leading performance
at an accelerator power of 2 MW. This technical capability translates into a very broad range of scientific
capabilities. The composition of the instrument suite has been chosen to maximise the breadth and depth
of the scientific impact o
CNS Delivery Via Adsorptive Transcytosis
Adsorptive-mediated transcytosis (AMT) provides a means for brain delivery of medicines across the blood-brain barrier (BBB). The BBB is readily equipped for the AMT process: it provides both the potential for binding and uptake of cationic molecules to the luminal surface of endothelial cells, and then for exocytosis at the abluminal surface. The transcytotic pathways present at the BBB and its morphological and enzymatic properties provide the means for movement of the molecules through the endothelial cytoplasm. AMT-based drug delivery to the brain was performed using cationic proteins and cell-penetrating peptides (CPPs). Protein cationization using either synthetic or natural polyamines is discussed and some examples of diamine/polyamine modified proteins that cross BBB are described. Two main families of CPPs belonging to the Tat-derived peptides and Syn-B vectors have been extensively used in CPP vector-mediated strategies allowing delivery of a large variety of small molecules as well as proteins across cell membranes in vitro and the BBB in vivo. CPP strategy suffers from several limitations such as toxicity and immunogenicity—like the cationization strategy—as well as the instability of peptide vectors in biological media. The review concludes by stressing the need to improve the understanding of AMT mechanisms at BBB and the effectiveness of cationized proteins and CPP-vectorized proteins as neurotherapeutics
Measurement of the W-Pair Production Cross Section and W-Decay Branching Fractions in Interactions at = 189 GeV
The data collected by the L3 experiment at LEP at a centre-of-mass energy of are used to measure the W-pair production cross section and the W-boson decay branching fractions. These data correspond to an integrated luminosity of 176.8~pb. The total cross section for W-pair production, combining all final states, is measured to be ~pb. Including our data collected at lower centre-of-mass energies, the hadronic branching fraction of the W-boson is determined to be . The results agree with the Standard Model predictions.The data collected by the L3 experiment at LEP at a centre-of-mass energy of 188.6 GeV are used to measure the W-pair production cross section and the W-boson decay branching fractions. These data correspond to an integrated luminosity of 176.8pb^-1. The total cross section for W-pair production, combining all final states, is measured to be sigma_WW = 16.24 +/- 0.37(stat.) +/- 0.22(syst.) pb. Including our data collected at lower centre-of-mass energies, the hadronic branching fraction of the W-boson is determined to be B(W ->qq) = [68.20 +/- 0.68 (stat.) +/- 0.33 (syst.) ] %. The results agree with the Standard Model predictions.The data collected by the L3 experiment at LEP at a centre-of-mass energy of 188.6 GeV are used to measure the W-pair production cross section and the W-boson decay branching fractions. These data correspond to an integrated luminosity of 176.8 pb −1 . The total cross section for W-pair production, combining all final states, is measured to be σ WW =16.24±0.37 (stat.)±0.22 (syst.) pb. Including our data collected at lower centre-of-mass energies, the hadronic branching fraction of the W-boson is determined to be B (W→qq)=[68.20±0.68 (stat.)±0.33 (syst.)]%. The results agree with the Standard Model predictions
Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial
Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p
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