22 research outputs found

    Characterization of the near-Earth Asteroid 2002NY40

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    In August 2002, the near-Earth asteroid 2002 NY40, made its closest approach to the Earth. This provided an opportunity to study a near-Earth asteroid with a variety of instruments. Several of the telescopes at the Maui Space Surveillance System were trained at the asteroid and collected adaptive optics images, photometry and spectroscopy. Analysis of the imagery reveals the asteroid is triangular shaped with significant self-shadowing. The photometry reveals a 20-hour period and the spectroscopy shows that the asteroid is a Q-type

    Managerial Power, Stock-Based Compensation, and Firm Performance: Theory and Evidence

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    We study theoretically and empirically the relation among CEO power, CEO pay and firm performance. Our theoretical model follows the rent extraction view of CEO compensation put forward by the managerial power theory. We test our theoretical findings using the sample of S&P1500 firms. The predicted relation between power and pay is largely supported. However, the relation between power and firm performance has mixed support, suggesting that, while the managerial power theory has relevance in explaining the relation between power and pay, the scope of power needs to be broadened for better understanding of how managerial power affects firm performance

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    Ottawa Panel Evidence-Based Clinical Practice Guidelines for the Management of Osteoarthritis in Adults Who Are Obese or Overweight

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    Background and Purpose. The objective of this review was to construct an updated evidence-based clinical practice guideline on the use of physical activity and diet for the management of osteoarthritis (OA) in adults (\u3e18 years of age) who are obese or overweight (body mass index ≥25 kg/m2). Data Sources. Articles were extracted from the following databases: MEDLINE, EMBASE (Current Contents), SPORTDiscus, SUM, Scopus, CINAHL, AMED, BIOMED, PubMed, ERIC, the Cochrane Controlled Trials, and PEDro. Study Selection. The Ottawa Panel and research assistance team strictly applied the inclusion and exclusion criteria from previous Ottawa Panel publications. Data Extraction. An a priori literature search was conducted for articles related to obesity and OA of the lower extremities that were published from January 1, 1966, to November 30, 2010. Inclusion criteria and the methods to grade the recommendations were created by the Ottawa Panel. Data Synthesis. Recommendations were graded based on the strength of evidence (A, B, C, C+ D, D+ or D-as well as experimental design (I for randomized controlled trials and II for nonrandomized studies). In agreement with previous Ottawa Panel methods, Cochrane Collaboration methods were utilized for statistical analysis. Clinical significance was established by an improvement of ≥15% in the experimental group compared with the control group. There were a total of 79 recommendations from 9 articles. From these recommendations, there were 36 positive recommendations: 21 grade A and 15 grade C+ There were no grade B recommendations, and all recommendations were of clinical benefit. Limitations. Further research is needed, as more than half of the trials were of low methodological quality. Conclusions. This review suggests that physical activity and diet programs are beneficial, specifically for pain relief (9 grade A recommendations) and improved functional status (6 grade A and 7 grade C+ recommendations), for adults with OA who are obese or overweight. The Ottawa Panel was able to demonstrate that when comparing physical activity alone, diet alone, physical activity combined with diet, and control groups, the intervention including physical activity and diet produced the most beneficial results. © 2011 American Physical Therapy Association

    ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97

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    Abstract The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributes with ASPSCR1::TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrate the oncogenic transcriptional signature of ASPSCR1::TFE3, by facilitating assembly of higher-order chromatin conformation structures demonstrated by HiChIP. Finally, ASPSCR1::TFE3 and VCP demonstrate co-dependence for cancer cell proliferation and tumorigenesis in vitro and in ASPS and RCC mouse models, underscoring VCP’s potential as a novel therapeutic target
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