We report the discoveries of three transiting exoplanets. WASP-91b is a warm Jupiter (1.34 MJup, 1.03 RJup) in a 2.8-day orbit around a metal-rich K3 star. WASP-105b is a warm Jupiter (1.8 MJup, 0.96 ...RJup) in a 7.9-day orbit around a metal-rich K2 star. WASP-107b is a warm super-Neptune/sub-Saturn (0.12 MJup, 0.94 RJup) in a 5.7-day orbit around a solar-metallicity K6 star. Considering that giant planets seem to be more common around stars of higher metallicity and stars of higher mass, it is notable that the hosts are all metal-rich, late-type stars. With orbital separations that place both WASP-105b and WASP-107b in the weak-tide regime, measurements of the alignment between the planets’ orbital axes and their stars’ spin axes may help us to understand the inward migration of short-period, giant planets. The mass of WASP-107b (2.2 MNep, 0.40 MSat) places it in the transition region between the ice giants and gas giants of the Solar System. Its radius of 0.94 RJup suggests that it is a low-mass gas giant with a H/He-dominated composition. The planet thus sets a lower limit of 2.2 MNep on the planetary mass above which large gaseous envelopes can be accreted and retained by proto-planets on their way to becoming gas giants. We may discover whether WASP-107b more closely resembles an ice giant or a gas giant by measuring its atmospheric metallicity via transmission spectroscopy, for which WASP-107b is a very good target.
OPTN/SRTR 2017 Annual Data Report: Heart Colvin, M.; Smith, J. M.; Hadley, N. ...
American journal of transplantation,
February 2019, 2019-02-00, 20190201, Letnik:
19, Številka:
S2
Journal Article
Recenzirano
Odprti dostop
In 2017, 3273 heart transplants were performed in the United States. New listings continued to increase, and 3769 new adults were listed for heart transplant in 2017. Over the past decade, ...posttransplant mortality has declined. The number of new pediatric listings increased over the past decade, as did the number of pediatric heart transplants, although some fluctuation has occurred more recently. New listings for pediatric heart transplants increased from 481 in 2007 to 623 in 2017. The number of pediatric heart transplants performed each year increased from 330 in 2007 to 432 in 2017, slightly fewer than in 2016. Short‐term and long‐term mortality improved. Among pediatric patients who underwent transplant between 2015‐2016, 4.8% had died by 6 months and 6.2% by 1 year.
The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a ...full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5
σ
, for all
δ
CP
values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3
σ
(5
σ
) after an exposure of 5 (10) years, for 50% of all
δ
CP
values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to
sin
2
2
θ
13
to current reactor experiments.
The Phoenix Mars Lander detected a larger number of short (∼20 s) pressure drops that probably indicate the passage of convective vortices or dust devils. Near‐continuous pressure measurements have ...allowed for monitoring the frequency of these events, and data from other instruments and orbiting spacecraft give information on how these pressure events relate to the seasons and weather phenomena at the Phoenix landing site. Here 502 vortices were identified with a pressure drop larger than 0.3 Pa occurring in the 151 sol mission (Ls 76 to 148). The diurnal distributions show a peak in convective vortices around noon, agreeing with current theory and previous observations. The few events detected at night might have been mechanically forced by turbulent eddies caused by the nearby Heimdal crater. A general increase with major peaks in the convective vortex activity occurs during the mission, around Ls = 111. This correlates with changes in midsol surface heat flux, increasing wind speeds at the landing site, and increases in vortex density. Comparisons with orbiter imaging show that in contrast to the lower latitudes on Mars, the dust devil activity at the Phoenix landing site is influenced more by active weather events passing by the area than by local forcing.
Summary Background Present interferon-based standard of care treatment for chronic hepatitis C virus (HCV) infection is limited by both efficacy and tolerability. We assessed the safety, ...tolerability, and antiviral activity of an all-oral combination treatment with two experimental anti-HCV drugs—RG7128, a nucleoside polymerase inhibitor; and danoprevir, an NS3/4A protease inhibitor—in patients with chronic HCV infection. Methods Patients from six centres in New Zealand and Australia who were chronically infected with HCV genotype 1 received up to 13 days oral combination treatment with RG7128 (500 mg or 1000 mg twice daily) and danoprevir (100 mg or 200 mg every 8 h or 600 mg or 900 mg twice daily) or placebo. Eligible patients were sequentially enrolled into one of seven treatment cohorts and were randomly assigned by interactive voice or web response system to either active treatment or placebo. Patients were separately randomly assigned within each cohort with a block size that reflected the number of patients in the cohort and the ratio of treatment to placebo. The random allocation schedule was computer generated. Dose escalation was started in HCV treatment-naive patients; standard of care treatment-experienced patients, including previous null responders, were enrolled in higher-dose danoprevir cohorts. Investigators, personnel at the study centre, and patients were masked to treatment allocation. However, the pharmacist who prepared the doses, personnel involved in pharmacokinetic sample analyses, statisticians who prepared data summaries, and the clinical pharmacologists who reviewed the data before deciding to initiate dosing in the next cohort were not masked to treatment allocation. The primary outcome was change in HCV RNA concentration from baseline to day 14 in patients who received 13 days of combination treatment. All patients who completed treatment with the study drugs were included in the analyses. This study is registered with ClinicalTrials.gov , NCT00801255. Findings 88 patients were randomly assigned to a study drug treatment regimen (n=74 over seven treatment groups; 73 received at least one dose of study drug) or to placebo (n=14, all of whom received at least one dose). The median change in HCV RNA concentration from baseline to day 14 ranged from −3·7 to −5·2 log10 IU/mL in the cohorts that received 13 days of combination treatment. At the highest combination doses tested (1000 mg RG7128 and 900 mg danoprevir twice daily), the median change in HCV RNA concentration from baseline to day 14 was −5·1 log10 IU/mL (IQR −5·6 to −4·7) in treatment-naive patients and −4·9 log10 IU/mL in previous standard of care null responders (−5·2 to −4·5) compared with an increase of 0·1 log10 IU/mL in the placebo group. The combination of RG7128 and danoprevir was well tolerated with no treatment-related serious or severe adverse events, no grade 3 or 4 changes in laboratory parameters, and no safety-related treatment discontinuations. Interpretation This oral combination of a nucleoside analogue polymerase inhibitor and protease inhibitor holds promise as an interferon-free treatment for chronic HCV. Funding Roche Palo Alto.
The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced ...prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged.
Hematoma expansion (HE) is a surrogate marker in intracerebral hemorrhage (ICH) trials. However, the amount of HE necessary to produce poor outcomes in an individual is unclear; there is no agreement ...on a clinically meaningful definition of HE. We compared commonly used definitions of HE in their ability to predict poor outcome as defined by various cutpoints on the modified Rankin Scale (mRS).
In this cohort study, we analyzed 531 patients with ICH from the Virtual International Stroke Trials Archive. Primary outcome was mRS at 90 days, dichotomized into 0-3 vs 4-6. Secondary outcomes included other mRS cutpoints and mRS "shift analysis." Sensitivity, specificity, and predictive values for commonly used HE definitions were calculated.
Between 13% and 32% of patients met the commonly used HE definitions. All definitions independently predicted poor outcome; positive predictive values increased with higher growth cutoffs but at the expense of lower sensitivities. All HE definitions showed higher specificity than sensitivity. Absolute growth cutoffs were more predictive than relative cutoffs when mRS 5-6 or 6 was defined as "poor outcome."
HE robustly predicts poor outcome regardless of the growth definition or the outcome definition. The highest positive predictive values are obtained when using an absolute growth definition to predict more severe outcomes. Given that only a minority of patients may have clinically relevant HE, hemostatic ICH trials may need to enroll a large number of patients, or select for a population that is more likely to have HE.
We introduce the antibody landscape, a method for the quantitative analysis of antibodymediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among ...pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.
Cardiac complications secondary to iron overload are the leading cause of death in beta-thalassemia major. Approximately two thirds of patients maintained on the parenteral iron chelator deferoxamine ...have myocardial iron loading. The oral iron chelator deferiprone has been demonstrated to remove myocardial iron, and it has been proposed that in combination with deferoxamine it may have additional effect.
Myocardial iron loading was assessed with the use of myocardial T2* cardiovascular magnetic resonance in 167 patients with thalassemia major receiving standard maintenance chelation monotherapy with subcutaneous deferoxamine. Of these patients, 65 with mild to moderate myocardial iron loading (T2* 8 to 20 ms) entered the trial with continuation of subcutaneous deferoxamine and were randomized to receive additional oral placebo (deferoxamine group) or oral deferiprone 75 mg/kg per day (combined group). The primary end point was the change in myocardial T2* over 12 months. Secondary end points of endothelial function (flow-mediated dilatation of the brachial artery) and cardiac function were also measured with cardiovascular magnetic resonance. There were significant improvements in the combined treatment group compared with the deferoxamine group in myocardial T2* (ratio of change in geometric means 1.50 versus 1.24; P=0.02), absolute left ventricular ejection fraction (2.6% versus 0.6%; P=0.05), and absolute endothelial function (8.8% versus 3.3%; P=0.02). There was also a significantly greater improvement in serum ferritin in the combined group (-976 versus -233 microg/L; P<0.001).
In comparison to the standard chelation monotherapy of deferoxamine, combination treatment with additional deferiprone reduced myocardial iron and improved the ejection fraction and endothelial function in thalassemia major patients with mild to moderate cardiac iron loading.
OPTN/SRTR 2018 Annual Data Report: Heart Colvin, M.; Smith, J. M.; Hadley, N. ...
American journal of transplantation,
January 2020, 2020-01-00, 20200101, Letnik:
20, Številka:
s1
Journal Article
Recenzirano
Odprti dostop
The new adult heart allocation policy was approved in 2016 and implemented in October 2018, so its effect was not yet evident in 2018 data. However, the more granular data being collected are ...anticipated to allow for improved analyses. In 2018, new listings continued to increase; 3883 new adult and 685 new pediatric candidates were added. In 2018, 3440 heart transplants were performed, an increase of 167 over 2017; 473 transplants occurred in pediatric recipients and 2967 in adult recipients. Short‐term and long‐term posttransplant mortality improved. Overall 1‐year survival for adults who underwent heart transplant in 2011‐2013 was 90.3%, 3‐year survival was 84.7%, and 5‐year survival was 79.6%. Mortality rates for pediatric recipients were 4.5% at 6 months and in 5.9% at 1 year posttransplant, 12.5% at 3 years for transplants in 2014‐2015, 14.8% at 5 years for transplants in 2012‐2013, and 29.8% at 10 years for transplants performed in 2008‐2009.
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