Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial†

Aim High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. Objective: To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). Design and setting A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2–5) weeks after the last study infusion. Patients Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Intervention Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. Main outcome measures The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. Results: The nominal change in the total atheroma volume (adjusted means) was −2.71, −3.13, −1.50, and −3.05 mm3 with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, −0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was −0.022, −0.036, −0.022, and −0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was −0.51, 2.65, 0.71, and −0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. Conclusion: CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other populations could favourably affect atherosclerosis must await further study. Name of the trial registry: Clinicaltrials.gov; Registry's URL: http://clinicaltrials.gov/ct2/show/NCT01201837?term=cer-001&rank=2; Trial registration number: NCT01201837

Measurement of the flavour composition of dijet events in pp collisions at root s=7 TeV with the ATLAS detector

This paper describes a measurement of the flavour composition of dijet events produced in pp collisions at √s=7 TeV using the ATLAS detector. The measurement uses the full 2010 data sample, corresponding to an integrated luminosity of 39 pb−1. Six possible combinations of light, charm and bottom jets are identified in the dijet events, where the jet flavour is defined by the presence of bottom, charm or solely light flavour hadrons in the jet. Kinematic variables, based on the properties of displaced decay vertices and optimised for jet flavour identification, are used in a multidimensional template fit to measure the fractions of these dijet flavour states as functions of the leading jet transverse momentum in the range 40 GeV to 500 GeV and jet rapidity |y|<2.1. The fit results agree with the predictions of leading- and next-to-leading-order calculations, with the exception of the dijet fraction composed of bottom and light flavour jets, which is underestimated by all models at large transverse jet momenta. The ability to identify jets containing two b-hadrons, originating from e.g. gluon splitting, is demonstrated. The difference between bottom jet production rates in leading and subleading jets is consistent with the next-to-leading-order predictions

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 8 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three leptons and missing transverse momentum is presented. The analysis is based on 20.3 fb−1 of s√ = 8 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with the Standard Model expectations and limits are set in R-parity-conserving phenomenological Minimal Supersymmetric Standard Models and in simplified supersymmetric models, significantly extending previous results. For simplified supersymmetric models of direct chargino (χ˜±1) and next-to-lightest neutralino (χ˜02) production with decays to lightest neutralino (χ˜01) via either all three generations of sleptons, staus only, gauge bosons, or Higgs bosons, (χ˜±1) and (χ˜02) masses are excluded up to 700 GeV, 380 GeV, 345 GeV, or 148 GeV respectively, for a massless (χ˜01

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Search for supersymmetry at √S=8TeV in final states with jets and two same-sign leptons or three leptons with the ATLAS detector

A search for strongly produced supersymmetric particles is conducted using signatures involving multiple energetic jets and either two isolated leptons (e or μ) with the same electric charge, or at least three isolated leptons. The search also utilises jets originating from b-quarks, missing transverse momentum and other observables to extend its sensitivity. The analysis uses a data sample corresponding to a total integrated luminosity of 20.3 fb−1 of √s = 8 TeV proton-proton collisions recorded with the ATLAS detector at the Large Hadron Collider in 2012. No deviation from the Standard Model expectation is observed. New or significantly improved exclusion limits are set on a wide variety of supersymmetric models in which the lightest squark can be of the first, second or third generations, and in which R-parity can be conserved or violated

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Measurement of the production of a W boson in association with a charm quark in pp collisions at √s = 7 TeV with the ATLAS detector

The production of a W boson in association with a single charm quark is studied using 4.6 fb−1 of ppcollision data at √s= 7 TeV collected with the ATLAS detector at the Large Hadron Collider. In events in which a Wboson decays to an electron or muon, the charm quark is tagged either by its semileptonic decay to a muon or by the presence of a charmed meson. The integrated and differential cross sections as a function of the pseudorapidity of the lepton from the W-boson decay are measured. Results are compared to the predictions of next-to-leading-order QCD calculations obtained from various parton distribution function parameterisations. The ratio of the strange-to-down sea-quark distributions is determined to be0.96+0.26−0.30at Q 2 = 1.9 GeV2, which supports the hypothesis of an SU(3)-symmetric composition of the light-quark sea. Additionally, the cross-section ratio σ(W + +c¯)/σ(W − + c) is compared to the predictions obtained using parton distribution function parameterisations with different assumptions about thes−s¯quark asymmetry

Search for dark matter candidates and large extra dimensions in events with a jet and missing transverse momentum with the ATLAS detector

A search for new phenomena in events with a high-energy jet and large missing transverse momentum is performed using data from proton-proton collisions at s√=7TeV with the ATLAS experiment at the Large Hadron Collider. Four kinematic regions are explored using a dataset corresponding to an integrated luminosity of 4.7 fb−1. No excess of events beyond expectations from Standard Model processes is observed, and limits are set on large extra dimensions and the pair production of dark matter particles

Search for direct production of charginos, neutralinos and sleptons in final states with two leptons and missing transverse momentum in pp collisions at √s = 8TeV with the ATLAS detector

Searches for the electroweak production of charginos, neutralinos and sleptons in final states characterized by the presence of two leptons (electrons and muons) and missing transverse momentum are performed using 20.3 fb−1 of proton-proton collision data at √s= 8 TeV recorded with the ATLAS experiment at the Large Hadron Collider. No significant excess beyond Standard Model expectations is observed. Limits are set on the masses of the lightest chargino, next-to-lightest neutralino and sleptons for different lightest-neutralino mass hypotheses in simplified models. Results are also interpreted in various scenarios of the phenomenological Minimal Supersymmetric Standard Model

Measurement of the production cross section of prompt j/psi mesons in association with a W (+/-) boson in pp collisions root s=7 TeV with the ATLAS detector

The process pp -> W (+/-) J/psi provides a powerful probe of the production mechanism of charmonium in hadronic collisions, and is also sensitive to multiple parton interactions in the colliding protons. Using the 2011 ATLAS dataset of 4.5 fb(-1) of root s= 7 TeV pp collisions at the LHC, the first observation is made of the production of W (+/-) + prompt J/psi events in hadronic collisions, using W (+/-) -> mu nu(mu) and J/psi -> mu(+)mu(-) center dot A yield of W (+/-) + prompt J/psi events is observed, with a statistical significance of 5.1 sigma. The production rate as a ratio to the inclusive W (+/-) boson production rate is measured, and the double parton scattering contribution to the cross section is estimated