Origins Space Telescope: Baseline mission concept

The Origins Space Telescope will trace the history of our origins from the time dust and heavy elements permanently altered the cosmic landscape to present-day life. How did galaxies evolve from the earliest galactic systems to those found in the Universe today? How do habitable planets form? How common are life-bearing worlds? To answer these alluring questions, Origins will operate at mid-and far-infrared (IR) wavelengths and offer powerful spectroscopic instruments and sensitivity three orders of magnitude better than that of the Herschel Space Observatory, the largest telescope flown in space to date. We describe the baseline concept for Origins recommended to the 2020 US Decadal Survey in Astronomy and Astrophysics. The baseline design includes a 5.9-m diameter telescope cryocooled to 4.5 K and equipped with three scientific instruments. A mid-infrared instrument (Mid-Infrared Spectrometer and Camera Transit spectrometer) will measure the spectra of transiting exoplanets in the 2.8 to 20 μm wavelength range and offer unprecedented spectrophotometric precision, enabling definitive exoplanet biosignature detections. The far-IR imager polarimeter will be able to survey thousands of square degrees with broadband imaging at 50 and 250 μm. The Origins Survey Spectrometer will cover wavelengths from 25 to 588 μm, making wide-area and deep spectroscopic surveys with spectral resolving power R ∼ 300, and pointed observations at R ∼ 40,000 and 300,000 with selectable instrument modes. Origins was designed to minimize complexity. The architecture is similar to that of the Spitzer Space Telescope and requires very few deployments after launch, while the cryothermal system design leverages James Webb Space Telescope technology and experience. A combination of current-state-of-the-art cryocoolers and next-generation detector technology will enable Origins\u27 natural background-limited sensitivity

Highly-parallelized simulation of a pixelated LArTPC on a GPU

The rapid development of general-purpose computing on graphics processing units (GPGPU) is allowing the implementation of highly-parallelized Monte Carlo simulation chains for particle physics experiments. This technique is particularly suitable for the simulation of a pixelated charge readout for time projection chambers, given the large number of channels that this technology employs. Here we present the first implementation of a full microphysical simulator of a liquid argon time projection chamber (LArTPC) equipped with light readout and pixelated charge readout, developed for the DUNE Near Detector. The software is implemented with an end-to-end set of GPU-optimized algorithms. The algorithms have been written in Python and translated into CUDA kernels using Numba, a just-in-time compiler for a subset of Python and NumPy instructions. The GPU implementation achieves a speed up of four orders of magnitude compared with the equivalent CPU version. The simulation of the current induced on 10^3 pixels takes around 1 ms on the GPU, compared with approximately 10 s on the CPU. The results of the simulation are compared against data from a pixel-readout LArTPC prototype

Clinical characteristics and outcomes of young and very young adults with heart failure: the CHARM programme

<p>Objectives: To determine the characteristics and outcomes of young adults with heart failure (HF).</p> <p>Background: Few studies have focused on young and very young adults with HF.</p> <p>Methods: Patients were categorized into 5 age groups: 20-39, 40-49, 50-59, 60-69, and ≥70 years.</p> <p>Results: The youngest patients with HF were more likely to be obese (youngest vs. oldest: BMI≥35kg/m2: 23% vs. 6%), of black ethnicity (18% vs. 2%), and have idiopathic dilated cardiomyopathy (IDCM 62% vs. 9%) (all p<0.0001). They were less likely to adhere to medication (non-adherence in youngest vs. oldest: 24% vs. 7%, p=0.001), salt intake and other dietary measures (21% vs. 9%, p=0.002). The youngest patients were less likely to have clinical and radiological signs of HF during hospitalization. Quality of life was worst but all-cause mortality was lowest in the youngest age group (3 years mortality rates across the respective age categories: 12%, 13%, 13%, 19%, and 31%). Compared to the referent age group of 60-69 years, both all-cause and cardiovascular mortality were lower in the youngest group even after multivariable adjustment (respective HR 0.60 (0.36-1.00) [p=0.049] and 0.71 (0.42-1.18) [p=0.186]). Three-year HF hospitalisation rates were 24%, 15%, 15%, 22% and 28% in age categories 20-39, 40-49, 50-59, 60-69 and ≥70 years respectively (p<0.0001). Conclusion: Beyond divergent etiology and comorbidities, younger patients exhibit striking differences in presentation and outcomes compared with older counterparts. Clinical and radiological signs of HF are less common, yet quality of life more significantly impaired. Fatal and non-fatal outcomes are discordant, with better survival despite higher hospitalization rates.</p&gt

Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme

Aims To determine whether the risk of adverse cardiovascular (CV) outcomes associated with diabetes differs in patients with low and preserved ejection fraction (EF) heart failure (HF). Methods and results We analysed outcomes in the Candesartan in Heart failure—Assessment of Reduction in Mortality and morbidity (CHARM) programme which randomized 7599 patients with symptomatic HF and a broad range of EF. The prevalence of diabetes was 28.3% in patients with preserved EF (>40%) and 28.5% in those with low EF (≤40%). Diabetes was associated with a greater relative risk of CV death or HF hospitalization in patients with preserved EF [hazard ratio (HR) 2.0 (1.70–2.36)] than in patients with low EF [HR 1.60 (1.44–1.77); interaction test P = 0.0009]. For all-cause mortality, the risk conferred by diabetes was similar in both low and preserved EF groups. The effect of candesartan in reducing CV morbidity and mortality outcomes was not modified by having diabetes at baseline (P = 0.09 test for interaction). Conclusion Diabetes was an independent predictor of CV morbidity and mortality in patients with HF, regardless of EF. The relative risk of CV death or HF hospitalization conferred by diabetes was significantly greater in patients with preserved when compared with those with low EF HF

Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation

Contains fulltext : 169768.pdf (publisher's version ) (Open Access)OBJECTIVE: We describe the incidence, location and management of non-major bleeding, and assess the association between non-major bleeding and clinical outcomes in patients with atrial fibrillation (AF) receiving anticoagulation therapy enrolled in Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE). METHODS: We included patients who received >/=1 dose of study drug (n=18 140). Non-major bleeding was defined as the first bleeding event considered to be clinically relevant non-major (CRNM) or minor bleeding, and not preceded by a major bleeding event. RESULTS: Non-major bleeding was three times more common than major bleeding (12.1% vs 3.8%). Like major bleeding, non-major bleeding was less frequent with apixaban (6.4 per 100 patient-years) than warfarin (9.4 per 100 patient-years) (adjusted HR 0.69, 95% CI 0.63 to 0.75). The most frequent sites of non-major bleeding were haematuria (16.4%), epistaxis (14.8%), gastrointestinal (13.3%), haematoma (11.5%) and bruising/ecchymosis (10.1%). Medical or surgical intervention was similar among patients with non-major bleeding on warfarin versus apixaban (24.7% vs 24.5%). A change in antithrombotic therapy (58.6% vs 50.0%) and permanent study drug discontinuation (5.1% (61) vs 3.6% (30), p=0.10) was numerically higher with warfarin than apixaban. CRNM bleeding was independently associated with an increased risk of overall death (adjusted HR 1.70, 95% CI 1.32 to 2.18) and subsequent major bleeding (adjusted HR 2.18, 95% CI 1.56 to 3.04). CONCLUSIONS: In ARISTOTLE, non-major bleeding was common and substantially less frequent with apixaban than with warfarin. CRNM bleeding was independently associated with a higher risk of death and subsequent major bleeding. Our results highlight the importance of any severity of bleeding in patients with AF treated with anticoagulation therapy and suggest that non-major bleeding, including minor bleeding, might not be minor. TRIAL REGISTRATION NUMBER: NCT00412984; post-results

Apixaban in patients with atrial fibrillation and prior coronary artery disease: Insights from the ARISTOTLE trial

Item does not contain fulltextBACKGROUND: A substantial portion of patients with atrial fibrillation (AF) also have coronary artery disease (CAD) and are at risk for coronary events. Warfarin is known to reduce these events, but increase the risk of bleeding. We assessed the effects of apixaban compared with warfarin in AF patients with and without prior CAD. METHODS AND RESULTS: In ARISTOTLE, 18,201 patients with AF were randomized to apixaban or warfarin. History of CAD was defined as documented CAD, prior myocardial infarction, and/or history of coronary revascularization. We analyzed baseline characteristics and clinical outcomes of patients with and without prior CAD and compared outcomes by randomized treatment using Cox models. A total of 6639 (36.5%) patients had prior CAD. These patients were more often male, more likely to have prior stroke, diabetes, and hypertension, and more often received aspirin at baseline (42.2% vs. 24.5%). The effects of apixaban were similar among patients with and without prior CAD on reducing stroke or systemic embolism and death from any cause (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.71-1.27, P for interaction=0.12; HR 0.96, 95% CI 0.81-1.13, P for interaction=0.28). Rates of myocardial infarction were numerically lower with apixaban than warfarin among patients with and without prior CAD. The effect of apixaban on reducing major bleeding and intracranial hemorrhage was consistent in patients with and without CAD. CONCLUSIONS: In patients with AF, apixaban more often prevented stroke or systemic embolism and death and caused less bleeding than warfarin, regardless of the presence of prior CAD. Given the common occurrence of AF and CAD and the higher rates of cardiovascular events and death, our results indicate that apixaban may be a better treatment option than warfarin for these high-risk patients

Clinical events after transitioning from apixaban versus warfarin to warfarin at the end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial

Item does not contain fulltextBACKGROUND: We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE. METHODS: At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA). Outcomes were assessed during the 30 days after stopping blinded study drug. RESULTS: Of the 6,809 patients in the apixaban group and 6,588 in the warfarin group who completed the trial on study drug, there were 21 strokes or systemic emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), with most of the imbalance between groups being after the first week. Similar results were seen in the first 30 days of the trial where warfarin-naive patients starting warfarin had a higher rate of stroke or systemic emboli (5.41%/year) than warfarin-experienced patients (1.42%/year), a pattern not seen when starting apixaban. No similar increase in events with apixaban versus warfarin was seen during temporary or permanent study drug discontinuation during the trial. CONCLUSIONS: The excess in thrombotic and bleeding events in the apixaban group after study drug discontinuation appears to be related to an increased risk associated with the initiation of a VKA rather than a direct effect of apixaban. Whether >/=2 days of apixaban bridging improves outcomes during VKA transition is unknown and deserves further evaluation

Percutaneous coronary intervention and antiplatelet therapy in patients with atrial fibrillation receiving apixaban or warfarin: Insights from the ARISTOTLE trial

Contains fulltext : 190525.pdf (publisher's version ) (Closed access)BACKGROUND: We assessed antiplatelet therapy use and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ARISTOTLE trial. METHODS: Patients were categorized based on the occurrence of PCI during follow-up (median 1.8 years); PCI details and outcomes post-PCI are reported. Of the 18,201 trial participants, 316 (1.7%) underwent PCI (152 in apixaban group, 164 in warfarin group). RESULTS: At the time of PCI, 84% (267) were on study drug (either apixaban or warfarin). Of these, 19% did not stop study drug during PCI, 49% stopped and restarted 5 days post-PCI. At 30 days post-PCI, 35% of patients received dual -antiplatelet therapy (DAPT), 23% received aspirin only, and 13% received a P2Y12 inhibitor only; 29% received no antiplatelet therapy. Triple therapy (DAPT + oral anticoagulant [OAC]) was used in 21% of patients, 23% received OAC only, 15% received OAC plus aspirin, and 9% received OAC plus a P2Y12 inhibitor; 32% received antiplatelet agents without OAC. Post-PCI, patients assigned to apixaban versus warfarin had numerically similar rates of major bleeding (5.93 vs 6.73 events/100 patient-years; P = .95) and stroke (2.74 vs 1.84 events/100 patient-years; P = .62). CONCLUSIONS: PCI occurred infrequently during follow-up. Most patients on study drug at the time of PCI remained on study drug in the peri-PCI period; 19% continued the study drug without interruption. Antiplatelet therapy use post-PCI was variable, although most patients received DAPT. Additional data are needed to guide the use of antithrombotics in patients undergoing PCI