To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical ...research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health.
Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials.
The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the US Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included (i) respect for the historical legacy of surgical valve guidelines; (ii) identification of pathophysiological mechanisms associated with clinical events; (iii) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended.
Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes.
ABSTRACT We report the detection of coherent pulsations from the ultraluminous X-ray source (ULX) NGC 7793 P13. The 0.42 s nearly sinusoidal pulsations were initially discovered in broadband X-ray ...observations using XMM-Newton and NuSTAR taken in 2016. We subsequently also found pulsations in archival XMM-Newton data taken in 2013 and 2014. The significant (>5 ) detection of coherent pulsations demonstrates that the compact object in P13 is a neutron star, and given the observed peak luminosity of 1040 erg s − 1 (assuming isotropy), it is well above the Eddington limit for a 1.4 M accretor. This makes P13 the second ULX known to be powered by an accreting neutron star. The pulse period varies between epochs, with a slow but persistent spin-up over the 2013-2016 period. This spin-up indicates a magnetic field of B 1.5 × 1012 G, typical of many Galactic accreting pulsars. The most likely explanation for the extreme luminosity is a high degree of beaming; however, this is difficult to reconcile with the sinusoidal pulse profile.
Magnesium hydride owns the largest share of publications on solid materials for hydrogen storage. The “Magnesium group” of international experts contributing to IEA Task 32 “Hydrogen Based Energy ...Storage” recently published two review papers presenting the activities of the group focused on magnesium hydride based materials and on Mg based compounds for hydrogen and energy storage. This review article not only overviews the latest activities on both fundamental aspects of Mg-based hydrides and their applications, but also presents a historic overview on the topic and outlines projected future developments. Particular attention is paid to the theoretical and experimental studies of Mg-H system at extreme pressures, kinetics and thermodynamics of the systems based on MgH2, nanostructuring, new Mg-based compounds and novel composites, and catalysis in the Mg based H storage systems. Finally, thermal energy storage and upscaled H storage systems accommodating MgH2 are presented.
•Historical overview of Mg-based hydrides.•Nanostructured Mg-based H storage materials prepared by mechanical alloying and reactive ball milling.•Thermodynamics and kinetics for Mg-based hydrides.•Catalysis in Mg-H system.•Mg-H system at high pressures: theoretical and experimental studies.
We assess evidence relevant to Earth's equilibrium climate sensitivity per doubling of atmospheric CO2, characterized by an effective sensitivity S . This evidence includes feedback process ...understanding, the historical climate record, and the paleoclimate record. An S value lower than 2 K is difficult to reconcile with any of the three lines of evidence. The amount of cooling during the Last Glacial Maximum provides strong evidence against values of S greater than 4.5 K. Other lines of evidence in combination also show that this is relatively unlikely. We use a Bayesian approach to produce a probability density (PDF) for S given all the evidence, including tests of robustness to difficult‐to‐quantify uncertainties and different priors. The 66% range is 2.6‐3.9 K for our Baseline calculation, and remains within 2.3‐4.5 K under the robustness tests; corresponding 5‐95% ranges are 2.3‐4.7 K, bounded by 2.0‐5.7 K (although such high‐confidence ranges should be regarded more cautiously). This indicates a stronger constraint on S than reported in past assessments, by lifting the low end of the range. This narrowing occurs because the three lines of evidence agree and are judged to be largely independent, and because of greater confidence in understanding feedback processes and in combining evidence. We identify promising avenues for further narrowing the range in S , in particular using comprehensive models and process understanding to address limitations in the traditional forcing‐feedback paradigm for interpreting past changes.
Aim
To assess the comparative efficacy and safety of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors in adults with type 2 diabetes.
Methods
We electronically searched randomized controlled trials ...(≥24 weeks) including canagliflozin, dapagliflozin or empagliflozin that were published up to 3 November 2015. Data were collected on cardiometabolic and safety outcomes and synthesized using network meta‐analyses.
Results
A total of 38 trials (23 997 participants) were included. Compared with placebo, all SGLT2 inhibitors reduced glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and blood pressure, and slightly increased HDL cholesterol. Canagliflozin 300 mg reduced HbA1c, FPG and systolic blood pressure and increased LDL cholesterol to a greater extent compared with other inhibitors at any dose. At their highest doses, canagliflozin 300 mg reduced: HbA1c by 0.2% 95% confidence interval (CI) 0.1–0.3 versus both dapagliflozin 10 mg and empagliflozin 25 mg; FPG by 0.6 mmol/l (95% CI 0.3–0.9) and 0.5 mmol/l (95% CI 0.1–0.8) versus dapagliflozin and empagliflozin, respectively; and systolic blood pressure by 2 mmHg (95% CI 1.0–3.0) versus dapagliflozin; and increased LDL cholesterol by 0.13 mmol/l (95% CI 0.03–0.23) and 0.15 mmol/l (95% CI 0.06–0.23) versus dapagliflozin and empagliflozin, respectively. The highest doses of inhibitors had similar effects on body weight reduction. Canagliflozin 300 and 100 mg increased the risk of hypoglycaemia versus placebo, dapagliflozin 10 mg and empagliflozin 10 mg odds ratios (ORs) 1.4–1.6. Dapagliflozin 10 mg increased the risk of urinary tract infection versus placebo and empagliflozin 25 mg (ORs 1.4). All inhibitors similarly increased the risk of genital infection (ORs 4–6 versus placebo).
Conclusions
Although they increase the risk of genital infection, SGLT2 inhibitors are effective in improving cardiometabolic markers in type 2 diabetes, with canagliflozin 300 mg performing better in this respect than other inhibitors. Further studies will clarify whether these differences are likely to translate into differing long‐term outcomes.
To assess the current status of climate models in simulating clouds, basic cloud climatologies from ten atmospheric general circulation models are compared with satellite measurements from the ...International Satellite Cloud Climatology Project (ISCCP) and the Clouds and Earth's Radiant Energy System (CERES) program. An ISCCP simulator is employed in all models to facilitate the comparison. Models simulated a four‐fold difference in high‐top clouds. There are also, however, large uncertainties in satellite high thin clouds to effectively constrain the models. The majority of models only simulated 30–40% of middle‐top clouds in the ISCCP and CERES data sets. Half of the models underestimated low clouds, while none overestimated them at a statistically significant level. When stratified in the optical thickness ranges, the majority of the models simulated optically thick clouds more than twice the satellite observations. Most models, however, underestimated optically intermediate and thin clouds. Compensations of these clouds biases are used to explain the simulated longwave and shortwave cloud radiative forcing at the top of the atmosphere. Seasonal sensitivities of clouds are also analyzed to compare with observations. Models are shown to simulate seasonal variations better for high clouds than for low clouds. Latitudinal distribution of the seasonal variations correlate with satellite measurements at >0.9, 0.6–0.9, and −0.2–0.7 levels for high, middle, and low clouds, respectively. The seasonal sensitivities of cloud types are found to strongly depend on the basic cloud climatology in the models. Models that systematically underestimate middle clouds also underestimate seasonal variations, while those that overestimate optically thick clouds also overestimate their seasonal sensitivities. Possible causes of the systematic cloud biases in the models are discussed.
Background. Beta-lactam antibiotics are a commonly used treatment for severe sepsis, with intermittent bolus dosing standard therapy, despite a strong theoretical rationale for continuous ...administration. The aim of this trial was to determine the clinical and pharmacokinetic differences between continuous and intermittent dosing in patients with severe sepsis. Methods. This was a prospective, double-blind, randomized controlled trial of continuous infusion versus intermittent bolus dosing of piperacillin-tazobactam, meropenem, and ticarcillin-clavulanate conducted in 5 intensive care units across Australia and Hong Kong. The primary pharmacokinetic outcome on treatment analysis was plasma antibiotic concentration above the minimum inhibitory concentration (MIC) on days 3 and 4. The assessed clinical outcomes were clinical response 7–14 days after study drug cessation, ICU-free days at day 28 and hospital survival. Results. Sixty patients were enrolled with 30 patients each allocated to the intervention and control groups. Plasma antibiotic concentrations exceeded the MIC in 82% of patients (18 of 22) in the continuous arm versus 29% (6 of 21) in the intermittent arm (P = .001). Clinical cure was higher in the continuous group (70% vs 43%; P = .037), but ICU-free days (19.5 vs 17 days; P = .14) did not significantly differ between groups. Survival to hospital discharge was 90% in the continuous group versus 80% in the intermittent group (P = .47). Conclusions. Continuous administration of beta-lactam antibiotics achieved higher plasma antibiotic concentrations than intermittent administration with improvement in clinical cure. This study provides a strong rationale for further multicenter trials with sufficient power to identify differences in patient-centered endpoints.
In a randomized trial, 1000 patients with severe aortic stenosis who were at low risk for death with surgery were assigned to undergo transcatheter aortic-valve replacement with a balloon-expandable ...valve or surgical aortic-valve replacement. At 1 year, the rate of death, stroke, or rehospitalization was significantly lower in the TAVR group.
We present a catalogue of ~3000 submillimetre sources detected ( greater than or equal to 3.5...) at 850 ...m over ~5 deg super( 2) surveyed as part of the James Clerk Maxwell Telescope (JCMT) ...SCUBA-2 Cosmology Legacy Survey (S2CLS). This is the largest survey of its kind at 850 ...m, increasing the sample size of 850 ...m selected submillimetre galaxies by an order of magnitude. The wide 850 ...m survey component of S2CLS covers the extragalactic fields: UKIDSS-UDS, COSMOS, Akari-NEP, Extended Groth Strip, Lockman Hole North, SSA22 and GOODS-North. The average 1... depth of S2CLS is 1.2 mJy beam super( -1), approaching the SCUBA-2 850 ...m confusion limit, which we determine to be ... 0.8 mJy beam super( -1). We measure the 850 ...m number counts, reducing the Poisson errors on the differential counts to approximately 4 per cent at S sub( 850) ... 3 mJy. With several independent fields, we investigate field-to-field variance, finding that the number counts on 0.5...-1... scales are generally within 50 per cent of the S2CLS mean for S sub( 850) > 3 mJy, with scatter consistent with the Poisson and estimated cosmic variance uncertainties, although there is a marginal (2...) density enhancement in GOODS-North. The observed counts are in reasonable agreement with recent phenomenological and semi-analytic models, although determining the shape of the faint-end slope (S sub( 850) < 3 mJy) remains a key test. The large solid angle of S2CLS allows us to measure the bright-end counts: at S sub( 850) > 10 mJy there are approximately 10 sources per square degree, and we detect the distinctive up-turn in the number counts indicative of the detection of local sources of 850 ...m emission, and strongly lensed high-redshift galaxies. All calibrated maps and the catalogue are made publicly available. (ProQuest: ... denotes formulae/symbols omitted.)
Based on phase-resolved broadband spectroscopy using XMM-Newton and NuSTAR, we report on a potential cyclotron resonant scattering feature (CRSF) at E ∼ 13 keV in the pulsed spectrum of the recently ...discovered ultraluminous X-ray source (ULX) pulsar NGC 300 ULX1. If this interpretation is correct, the implied magnetic field of the central neutron star is B ∼ 1012 G (assuming scattering by electrons), similar to that estimated from the observed spin-up of the star, and also similar to known Galactic X-ray pulsars. We discuss the implications of this result for the connection between NGC 300 ULX1 and the other known ULX pulsars, particularly in light of the recent discovery of a likely proton cyclotron line in another ULX, M51 ULX-8.
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