Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Search for light long-lived neutral particles from Higgs boson decays via vector-boson-fusion production from pp collisions at √s = 13 TeV with the ATLAS detector

A search is reported for long-lived dark photons with masses between 0.1 GeV and 15 GeV, from exotic decays of Higgs bosons produced via vector-boson-fusion. Events that contain displaced collimated Standard Model fermions reconstructed in the calorimeter or muon spectrometer are probed. This search uses the full LHC Run 2 (2015–2018) data sample collected in proton–proton collisions at √s = 13 TeV, corresponding to an integrated luminosity of 139 f b − 1 . Dominant backgrounds from Standard Model processes and non-collision sources are estimated using data-driven techniques. The observed event yields in the signal regions are consistent with the expected background. Upper limits on the Higgs boson to dark photon branching fraction are reported as a function of the dark photon mean proper decay length or of the dark photon mass and the coupling between the Standard Model and the potential dark sector. This search is combined with previous ATLAS searches obtained in the gluon–gluon fusion and WH production modes. A branching fraction above 10% is excluded at 95% CL for a 125 GeV Higgs boson decaying into two dark photons for dark photon mean proper decay lengths between 173 and 1296 mm and mass of 10 GeV

Combination of the W boson polarization measurements in top quark decays using ATLAS and CMS data at s = 8 TeV

Abstract: The combination of measurements of the W boson polarization in top quark decays performed by the ATLAS and CMS collaborations is presented. The measurements are based on proton-proton collision data produced at the LHC at a centre-of-mass energy of 8 TeV, and corresponding to an integrated luminosity of about 20 fb−1 for each experiment. The measurements used events containing one lepton and having different jet multiplicities in the final state. The results are quoted as fractions of W bosons with longitudinal (F0), left-handed (FL), or right-handed (FR) polarizations. The resulting combined measurements of the polarization fractions are F0 = 0.693 ± 0.014 and FL = 0.315 ± 0.011. The fraction FR is calculated from the unitarity constraint to be FR = −0.008 ± 0.007. These results are in agreement with the standard model predictions at next-to-next-to-leading order in perturbative quantum chromodynamics and represent an improvement in precision of 25 (29)% for F0 (FL) with respect to the most precise single measurement. A limit on anomalous right-handed vector (VR), and left- and right-handed tensor (gL, gR) tWb couplings is set while fixing all others to their standard model values. The allowed regions are [−0.11, 0.16] for VR, [−0.08, 0.05] for gL, and [−0.04, 0.02] for gR, at 95% confidence level. Limits on the corresponding Wilson coefficients are also derived

Determination of jet calibration and energy resolution in proton–proton collisions at s = 8 TeV using the ATLAS detector

Abstract: The jet energy scale, jet energy resolution, and their systematic uncertainties are measured for jets reconstructed with the ATLAS detector in 2012 using proton–proton data produced at a centre-of-mass energy of 8 TeV with an integrated luminosity of 20fb-1. Jets are reconstructed from clusters of energy depositions in the ATLAS calorimeters using the anti-kt algorithm. A jet calibration scheme is applied in multiple steps, each addressing specific effects including mitigation of contributions from additional proton–proton collisions, loss of energy in dead material, calorimeter non-compensation, angular biases and other global jet effects. The final calibration step uses several in situ techniques and corrects for residual effects not captured by the initial calibration. These analyses measure both the jet energy scale and resolution by exploiting the transverse momentum balance in γ + jet, Z + jet, dijet, and multijet events. A statistical combination of these measurements is performed. In the central detector region, the derived calibration has a precision better than 1% for jets with transverse momentum 150GeV<pT< 1500 GeV, and the relative energy resolution is (8.4±0.6)% for pT=100GeV and (23±2)% for pT=20GeV. The calibration scheme for jets with radius parameter R=1.0, for which jets receive a dedicated calibration of the jet mass, is also discussed

The ATLAS Data Acquisition and High Level Trigger system

This paper describes the data acquisition and high level trigger system of the ATLAS experiment at the Large Hadron Collider at CERN, as deployed during Run 1. Data flow as well as control, configuration and monitoring aspects are addressed. An overview of the functionality of the system and of its performance is presented and design choices are discussed

Search for scalar leptoquarks in pp\mathit{pp} collisions at s=13\sqrt{s}=13 TeV with the ATLAS experiment

An inclusive search for a new-physics signature of lepton-jet resonances has been performed by the ATLAS experiment. Scalar leptoquarks, pair-produced in pp collisions at s√ = 13 TeV at the large hadron collider, have been considered. An integrated luminosity of 3.2 fb(−)(1), corresponding to the full 2015 dataset was used. First (second) generation leptoquarks were sought in events with two electrons (muons) and two or more jets. The observed event yield in each channel is consistent with Standard Model background expectations. The observed (expected) lower limits on the leptoquark mass at 95% confidence level are 1100 and 1050 GeV (1160 and 1040 GeV) for first and second generation leptoquarks, respectively, assuming a branching ratio into a charged lepton and a quark of 100%. Upper limits on the aforementioned branching ratio are also given as a function of leptoquark mass. Compared with the results of earlier ATLAS searches, the sensitivity is increased for leptoquark masses above 860 GeV, and the observed exclusion limits confirm and extend the published results