Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Development of a Convolutional Neural Network Based Skull Segmentation in MRI Using Standard Tesselation Language Models

Segmentation is crucial in medical imaging analysis to help extract regions of interest (ROI) from different imaging modalities. The aim of this study is to develop and train a 3D convolutional neural network (CNN) for skull segmentation in magnetic resonance imaging (MRI). 58 gold standard volumetric labels were created from computed tomography (CT) scans in standard tessellation language (STL) models. These STL models were converted into matrices and overlapped on the 58 corresponding MR images to create the MRI gold standards labels. The CNN was trained with these 58 MR images and a mean ± standard deviation (SD) Dice similarity coefficient (DSC) of 0.7300 ± 0.04 was achieved. A further investigation was carried out where the brain region was removed from the image with the help of a 3D CNN and manual corrections by using only MR images. This new dataset, without the brain, was presented to the previous CNN which reached a new mean ± SD DSC of 0.7826 ± 0.03. This paper aims to provide a framework for segmenting the skull using CNN and STL models, as the 3D CNN was able to segment the skull with a certain precision

Acute effects of combined cycling and plyometrics on vertical jump performance in active males

The aim of this study was to analyze the acute effects of high vs low-intensity cycling efforts, combined with plyometrics, on vertical jump performance. Twenty-four physically active men (mean ±SD: 23 ± 2 years, 72.1 ± 10.1 kg, 1.73 ± 0.07 m) were randomly divided into two groups: experimental group (EXP, n = 16) and control group (CON, n = 8). EXP competed 2 experimental trials in a random order: (a) short high-intensity interval exercise (HI + Plyo) [5 × 10 s of cycling (“all-out”)/50 s active rest] or (b) low-intensity continuous exercise (LO + Plyo) [5 min of cycling at 75% of the HRmax)], along with 3 × 10 plyometric bounds (drop jumps)/1 min rest between sets. CON used a preconditioning activity of 13 min of low intensity cycling at ~60% of HRmax. Both EXP interventions significantly increased (p ≤ 0.05) the countermovement jump (CMJ) height at 1 min, 3 min, 6 min and 9 min compared to baseline, while the CON remained unchanged. There were no significant differences in CMJ performance enhancement between HI + Plyo (largest 11.2% at 9 min) and LO + Plyo (largest 15.0% at 3 min) at any time-point, suggesting that the plyometric component may be most important, with HR recovery taking slightly longer following HI + Plyo. The findings suggest that CMJ performance can be enhanced following high or low-intensity cycling combined with plyometric preconditioning activities in active males, the optimum recovery period likely to be individual-specific

Alirocumab and cardiovascular outcomes after acute coronary syndrome

BACKGROUN

Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome

BACKGROUN

Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora

International audienceThe Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/$c$ charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1$\pm0.6$% and 84.1$\pm0.6$%, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation

Reconstruction of interactions in the ProtoDUNE-SP detector with Pandora

International audienceThe Pandora Software Development Kit and algorithm libraries provide pattern-recognition logic essential to the reconstruction of particle interactions in liquid argon time projection chamber detectors. Pandora is the primary event reconstruction software used at ProtoDUNE-SP, a prototype for the Deep Underground Neutrino Experiment far detector. ProtoDUNE-SP, located at CERN, is exposed to a charged-particle test beam. This paper gives an overview of the Pandora reconstruction algorithms and how they have been tailored for use at ProtoDUNE-SP. In complex events with numerous cosmic-ray and beam background particles, the simulated reconstruction and identification efficiency for triggered test-beam particles is above 80% for the majority of particle type and beam momentum combinations. Specifically, simulated 1 GeV/$c$ charged pions and protons are correctly reconstructed and identified with efficiencies of 86.1$\pm0.6$% and 84.1$\pm0.6$%, respectively. The efficiencies measured for test-beam data are shown to be within 5% of those predicted by the simulation