Emission-Line Eclipse Mapping of Velocity Fields in Dwarf-Nova Accretion Disk

We propose a new method, emission-line eclipse mapping, to map the velocity fields of an accretion disk in position space. Quiescent dwarf novae usually exhibit double-peaked emission line profiles because of disk rotation. Since a part of the disk having a different line-of-sight velocity is successively obscured by a companion in eclipsing systems, they show time-varying line profiles. We calculate time changes of the emission line profiles, assuming Keplerian rotation fields (v_\phi\propto r^(-1/2) with r being the distance from the disk center) and the emissivity distribution of j \propto r^(-3/2). We, then, apply the usual eclipse mapping technique to the light curves at each of 12-24 wavelengths across the line center to map the region with the same line-of-sight velocity. The reconstructed images typically exhibit a `two-eye' pattern for high line-of-sight velocities and we can recover the relation, v_\phi \propto d^(-1/2), on the assumption of the axisymmetric disk, where d is the separation between the two `eyes'. We will be able to probe the Keplerian rotation law, the most fundamental assumption adopted in many disk models, by high-speed spectroscopic observations with 8-m class telescopes.Comment: 12pages, LaTeX with 26 eps figures using pasj00.cls and 21 JPEG figures, to appear in PASJ Vol. 54, No.3. Preprint in PDF format, including all color pictures, is available at ftp://ftp.kusastro.kyoto-u.ac.jp/pub/makoto/preprint/revmakpasj2.pdf.g

Predictors of Pulmonary Function Response to Treatment with Salmeterol/fluticasone in Patients with Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and responses to therapies are highly variable. The aim of this study was to identify the predictors of pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD. A total of 127 patients with stable COPD from the Korean Obstructive Lung Disease (KOLD) Cohort, which were prospectively recruited from June 2005 to September 2009, were analyzed retrospectively. The prediction models for the FEV1, FVC and IC/TLC changes after 3 months of treatment with salmeterol/fluticasone were constructed by using multiple, stepwise, linear regression analysis. The prediction model for the FEV1 change after 3 months of treatment included wheezing history, pre-bronchodilator FEV1, post-bronchodilator FEV1 change and emphysema extent on CT (R = 0.578). The prediction models for the FVC change after 3 months of treatment included pre-bronchodilator FVC, post-bronchodilator FVC change (R = 0.533), and those of IC/ TLC change after 3 months of treatment did pre-bronchodilator IC/TLC and post-bronchodilator FEV1 change (R = 0.401). Wheezing history, pre-bronchodilator pulmonary function, bronchodilator responsiveness, and emphysema extent may be used for predicting the pulmonary function response to 3 months of treatment with salmeterol/fluticasone in patients with COPD

Microlensig Binaries with Candidate Brown Dwarf Companions

Brown dwarfs are important objects because they may provide a missing link between stars and planets, two populations that have dramatically different formation history. In this paper, we present the candidate binaries with brown dwarf companions that are found by analyzing binary microlensing events discovered during 2004 - 2011 observation seasons. Based on the low mass ratio criterion of q < 0.2, we found 7 candidate events, including OGLE-2004-BLG-035, OGLE-2004-BLG-039, OGLE-2007-BLG-006, OGLE-2007-BLG-399/MOA-2007-BLG-334, MOA-2011-BLG-104/OGLE-2011-BLG-0172, MOA-2011-BLG-149, and MOA-201-BLG-278/OGLE-2011-BLG-012N. Among them, we are able to confirm that the companions of the lenses of MOA-2011-BLG-104/OGLE-2011-BLG-0172 and MOA-2011-BLG-149 are brown dwarfs by determining the mass of the lens based on the simultaneous measurement of the Einstein radius and the lens parallax. The measured mass of the brown dwarf companions are (0.02 +/- 0.01) M_Sun and (0.019 +/- 0.002) M_Sun for MOA-2011-BLG-104/OGLE-2011-BLG-0172 and MOA-2011-BLG-149, respectively, and both companions are orbiting low mass M dwarf host stars. More microlensing brown dwarfs are expected to be detected as the number of lensing events with well covered light curves increases with new generation searches.Comment: 10 pages, 9 figures, 4 table

Characterizing Lenses and Lensed Stars of High-Magnification Single-lens Gravitational Microlensing Events With Lenses Passing Over Source Stars

We present the analysis of the light curves of 9 high-magnification single-lens gravitational microlensing events with lenses passing over source stars, including OGLE-2004-BLG-254, MOA-2007-BLG-176, MOA-2007-BLG-233/OGLE-2007-BLG-302, MOA-2009-BLG-174, MOA-2010-BLG-436, MOA-2011-BLG-093, MOA-2011-BLG-274, OGLE-2011-BLG-0990/MOA-2011-BLG-300, and OGLE-2011-BLG-1101/MOA-2011-BLG-325. For all events, we measure the linear limb-darkening coefficients of the surface brightness profile of source stars by measuring the deviation of the light curves near the peak affected by the finite-source effect. For 7 events, we measure the Einstein radii and the lens-source relative proper motions. Among them, 5 events are found to have Einstein radii less than 0.2 mas, making the lenses candidates of very low-mass stars or brown dwarfs. For MOA-2011-BLG-274, especially, the small Einstein radius of $\theta_{\rm E}\sim 0.08$ mas combined with the short time scale of $t_{\rm E}\sim 2.7$ days suggests the possibility that the lens is a free-floating planet. For MOA-2009-BLG-174, we measure the lens parallax and thus uniquely determine the physical parameters of the lens. We also find that the measured lens mass of $\sim 0.84\ M_\odot$ is consistent with that of a star blended with the source, suggesting that the blend is likely to be the lens. Although we find planetary signals for none of events, we provide exclusion diagrams showing the confidence levels excluding the existence of a planet as a function of the separation and mass ratio.Comment: 14 pages, 12 figures, 5 table

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

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council