Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Measurement of the inclusive isolated-photon cross section in pp collisions at √s = 13 TeV using 36 fb−1 of ATLAS data

The differential cross section for isolated-photon production in pp collisions is measured at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC using an integrated luminosity of 36.1 fb. The differential cross section is presented as a function of the photon transverse energy in different regions of photon pseudorapidity. The differential cross section as a function of the absolute value of the photon pseudorapidity is also presented in different regions of photon transverse energy. Next-to-leading-order QCD calculations from Jetphox and Sherpa as well as next-to-next-to-leading-order QCD calculations from Nnlojet are compared with the measurement, using several parameterisations of the proton parton distribution functions. The predictions provide a good description of the data within the experimental and theoretical uncertainties. [Figure not available: see fulltext.

Operation and performance of the ATLAS semiconductor tracker in LHC Run 2

The semiconductor tracker (SCT) is one of the tracking systems for charged particles in the ATLAS detector. It consists of 4088 silicon strip sensor modules. During Run 2 (2015–2018) the Large Hadron Collider delivered an integrated luminosity of 156 fb-1 to the ATLAS experiment at a centre-of-mass proton-proton collision energy of 13 TeV. The instantaneous luminosity and pile-up conditions were far in excess of those assumed in the original design of the SCT detector. Due to improvements to the data acquisition system, the SCT operated stably throughout Run 2. It was available for 99.9% of the integrated luminosity and achieved a data-quality efficiency of 99.85%. Detailed studies have been made of the leakage current in SCT modules and the evolution of the full depletion voltage, which are used to study the impact of radiation damage to the modules

Operation and performance of the ATLAS semiconductor tracker in LHC Run 2

The semiconductor tracker (SCT) is one of the tracking systems for charged particles in the ATLAS detector. It consists of 4088 silicon strip sensor modules. During Run 2 (2015-2018) the Large Hadron Collider delivered an integrated luminosity of 156 fb−1 to the ATLAS experiment at a centre-of-mass proton-proton collision energy of 13 TeV. The instantaneous luminosity and pile-up conditions were far in excess of those assumed in the original design of the SCT detector. Due to improvements to the data acquisition system, the SCT operated stably throughout Run 2. It was available for 99.9% of the integrated luminosity and achieved a data-quality efficiency of 99.85%. Detailed studies have been made of the leakage current in SCT modules and the evolution of the full depletion voltage, which are used to study the impact of radiation damage to the modules

Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries

International audienceAbstract Introduction The Ebola virus disease (EVD) outbreak in 2014–2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. Multiple questions regarding the safety, immunogenicity, and efficacy of EVD vaccines remain unanswered. To address these gaps in the evidence base, the Partnership for Research on Ebola Vaccines (PREVAC) trial was designed. This paper describes the design, methods, and baseline results of the PREVAC trial and discusses challenges that led to different protocol amendments. Methods This is a randomized, double-blind, placebo-controlled phase 2 clinical trial of three vaccine strategies against the Ebola virus in healthy volunteers 1 year of age and above. The three vaccine strategies being studied are the rVSVΔG-ZEBOV-GP vaccine, with and without a booster dose at 56 days, and the Ad26.ZEBOV,MVA-FN-Filo vaccine regimen with Ad26.ZEBOV given as the first dose and the MVA-FN-Filo vaccination given 56 days later. There have been 4 versions of the protocol with those enrolled in Version 4.0 comprising the primary analysis cohort. The primary endpoint is based on the antibody titer against the Ebola virus surface glycoprotein measured 12 months following the final injection. Results From April 2017 to December 2018, a total of 5002 volunteers were screened and 4789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4789 participants, 2560 (53%) were adults and 2229 (47%) were children. Those < 18 years of age included 549 (12%) aged 1 to 4 years, 750 (16%) 5 to 11 years, and 930 (19%) aged 12–17 years. At baseline, the median (25th, 75th percentile) antibody titer to Ebola virus glycoprotein for 1090 participants was 72 (50, 116) EU/mL. Discussion The PREVAC trial is evaluating—placebo-controlled—two promising Ebola candidate vaccines in advanced stages of development. The results will address unanswered questions related to short- and long-term safety and immunogenicity for three vaccine strategies in adults and children. Trial registration ClinicalTrials.gov NCT02876328 . Registered on 23 August 2016

Operation and performance of the ATLAS semiconductor tracker in LHC Run 2

The semiconductor tracker (SCT) is one of the tracking systems for charged particles in the ATLAS detector. It consists of 4088 silicon strip sensor modules. During Run 2 (2015-2018) the Large Hadron Collider delivered an integrated luminosity of 156 fb−1 to the ATLAS experiment at a centre-of-mass proton-proton collision energy of 13 TeV. The instantaneous luminosity and pile-up conditions were far in excess of those assumed in the original design of the SCT detector. Due to improvements to the data acquisition system, the SCT operated stably throughout Run 2. It was available for 99.9% of the integrated luminosity and achieved a data-quality efficiency of 99.85%. Detailed studies have been made of the leakage current in SCT modules and the evolution of the full depletion voltage, which are used to study the impact of radiation damage to the modules. © 2022 CER

The ATLAS experiment at the CERN Large Hadron Collider: a description of the detector configuration for Run 3

Abstract The ATLAS detector is installed in its experimental cavern at Point 1 of the CERN Large Hadron Collider. During Run 2 of the LHC, a luminosity of  ℒ = 2 × 1034 cm-2 s-1 was routinely achieved at the start of fills, twice the design luminosity. For Run 3, accelerator improvements, notably luminosity levelling, allow sustained running at an instantaneous luminosity of  ℒ = 2 × 1034 cm-2 s-1, with an average of up to 60 interactions per bunch crossing. The ATLAS detector has been upgraded to recover Run 1 single-lepton trigger thresholds while operating comfortably under Run 3 sustained pileup conditions. A fourth pixel layer 3.3 cm from the beam axis was added before Run 2 to improve vertex reconstruction and b-tagging performance. New Liquid Argon Calorimeter digital trigger electronics, with corresponding upgrades to the Trigger and Data Acquisition system, take advantage of a factor of 10 finer granularity to improve triggering on electrons, photons, taus, and hadronic signatures through increased pileup rejection. The inner muon endcap wheels were replaced by New Small Wheels with Micromegas and small-strip Thin Gap Chamber detectors, providing both precision tracking and Level-1 Muon trigger functionality. Trigger coverage of the inner barrel muon layer near one endcap region was augmented with modules integrating new thin-gap resistive plate chambers and smaller-diameter drift-tube chambers. Tile Calorimeter scintillation counters were added to improve electron energy resolution and background rejection. Upgrades to Minimum Bias Trigger Scintillators and Forward Detectors improve luminosity monitoring and enable total proton-proton cross section, diffractive physics, and heavy ion measurements. These upgrades are all compatible with operation in the much harsher environment anticipated after the High-Luminosity upgrade of the LHC and are the first steps towards preparing ATLAS for the High-Luminosity upgrade of the LHC. This paper describes the Run 3 configuration of the ATLAS detector.</jats:p

The ATLAS experiment at the CERN Large Hadron Collider: a description of the detector configuration for Run 3

Abstract The ATLAS detector is installed in its experimental cavern at Point 1 of the CERN Large Hadron Collider. During Run 2 of the LHC, a luminosity of  ℒ = 2 × 1034 cm-2 s-1 was routinely achieved at the start of fills, twice the design luminosity. For Run 3, accelerator improvements, notably luminosity levelling, allow sustained running at an instantaneous luminosity of  ℒ = 2 × 1034 cm-2 s-1, with an average of up to 60 interactions per bunch crossing. The ATLAS detector has been upgraded to recover Run 1 single-lepton trigger thresholds while operating comfortably under Run 3 sustained pileup conditions. A fourth pixel layer 3.3 cm from the beam axis was added before Run 2 to improve vertex reconstruction and b-tagging performance. New Liquid Argon Calorimeter digital trigger electronics, with corresponding upgrades to the Trigger and Data Acquisition system, take advantage of a factor of 10 finer granularity to improve triggering on electrons, photons, taus, and hadronic signatures through increased pileup rejection. The inner muon endcap wheels were replaced by New Small Wheels with Micromegas and small-strip Thin Gap Chamber detectors, providing both precision tracking and Level-1 Muon trigger functionality. Trigger coverage of the inner barrel muon layer near one endcap region was augmented with modules integrating new thin-gap resistive plate chambers and smaller-diameter drift-tube chambers. Tile Calorimeter scintillation counters were added to improve electron energy resolution and background rejection. Upgrades to Minimum Bias Trigger Scintillators and Forward Detectors improve luminosity monitoring and enable total proton-proton cross section, diffractive physics, and heavy ion measurements. These upgrades are all compatible with operation in the much harsher environment anticipated after the High-Luminosity upgrade of the LHC and are the first steps towards preparing ATLAS for the High-Luminosity upgrade of the LHC. This paper describes the Run 3 configuration of the ATLAS detector.</jats:p