Obliquity Constraints on an Extrasolar Planetary-Mass Companion

We place the first constraints on the obliquity of a planetary-mass companion outside of the solar system. Our target is the directly imaged system 2MASS J01225093–2439505 (2M0122), which consists of a 120 Myr 0.4 M⊙ star hosting a 12–27 M_J companion at 50 au. We constrain all three of the system's angular-momentum vectors: how the companion spin axis, the stellar spin axis, and the orbit normal are inclined relative to our line of sight. To accomplish this, we measure projected rotation rates (v sin i) for both the star and the companion using new near-infrared high-resolution spectra with NIRSPEC at Keck Observatory. We combine these with a new stellar photometric rotation period from TESS and a published companion rotation period from Hubble Space Telescope to obtain spin-axis inclinations for both objects. We also fitted multiple epochs of astrometry, including a new observation with NIRC2/Keck, to measure 2M0122b's orbital inclination. The three line-of-sight inclinations place limits on the true de-projected companion obliquity and stellar obliquity. We find that while the stellar obliquity marginally prefers alignment, the companion obliquity tentatively favors misalignment. We evaluate possible origin scenarios. While collisions, secular spin–orbit resonances, and Kozai–Lidov oscillations are unlikely, formation by gravitational instability in a gravito-turbulent disk—the scenario favored for brown dwarf companions to stars—appears promising

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Effectiveness of Ambulatory Telemedicine Care in Older Adults: A Systematic Review

BACKGROUND: Disparities in healthcare access and delivery, caused by transportation and health workforce difficulties, negatively impact individuals living in rural areas. These challenges are especially prominent in older adults. DESIGN: We systematically evaluated the feasibility, acceptability, and effectiveness in providing telemedicine (TMed), searching the English‐language literature for studies (January 2012 to July 2018) in the following databases: Medline (PubMed); Cochrane Library (Wiley); Web of Science; CINAHL; EMBASE (Ovid); and PsycINFO (EBSCO). PARTICIPANTS: Older adults (mean age = 65 years or older, and none were younger than 60 years). INTERVENTIONS: Interventions consisted of live, synchronous, two‐way videoconferencing communication in nonhospital settings. All medical interventions were included. MEASUREMENTS: Quality assessment, using the Cochrane Collaboration\u27s Risk‐of‐Bias Tool, was applied on all included articles, including a qualitative summary of all articles. RESULTS: Of 6,616 citations, we reviewed the full text of 1173 articles, excluding 1047 that did not meet criteria. Of the 17 randomized controlled trials, the United States was the country with the most trials (6 [35%]), with cohort sizes ranging from 3 to 844 (median = 35) participants. Risk of bias among included studies varied from low to high. Our qualitative analysis suggests that TMed can improve health outcomes in older adults and that it could be used in this population. CONCLUSIONS: TMed is feasible and acceptable in delivering care to older adults. Research should focus on well‐designed randomized trials to overcome the high degree of bias observed in our synthesis. Clinicians should consider using TMed in routine practice to overcome barriers of distance and access to care

A Systematic Review of Dietary Supplements and Alternative Therapies for Weight Loss.

OBJECTIVE: Dietary supplements and alternative therapies are commercialized as a panacea for obesity/weight gain as a result of the minimal regulatory requirements in demonstrating efficacy. These products may indirectly undermine the value of guideline-driven obesity treatments. We systematically reviewed the literature of purported dietary supplements and alternative therapies for weight loss. METHODS: A systematic review evaluated the efficacy of dietary supplements and alternative therapies for weight loss aged ≥18 years. We searched Medline (Pubmed), Cochrane, Web of Science, CINAHL, EMBASE (Ovid), and PsychINFO (EBSCO). Risk of bias and results were summarized qualitatively. RESULTS: Of 20,504 citations, we reviewed 1,743 full-text articles, of which 315 were randomized controlled trials evaluating the efficacy of 14 purported dietary supplements, therapies or a combination thereof. Risk of bias and sufficiency of data varied widely. Few studies (n=52 [16.5%]) were classified low risk and sufficient to support efficacy. Of these, only 16 (31%) noted significant pre/post inter-group differences in weight (range: 0.3,4.93 kg). CONCLUSIONS: Dietary supplements and alternative therapies for weight loss have a limited, high-quality evidence-base of efficacy. Practitioners and patients should be aware of the scientific evidence of claims before recommending use

Modulation of macrophage inflammatory function through selective inhibition of the epigenetic reader protein SP140

Background: SP140 is a bromodomain-containing protein expressed predominantly in immune cells. Genetic polymorphisms and epigenetic modifications in the SP140 locus have been linked to Crohn’s disease (CD), suggesting a role in inflammation. Results: We report the development of the first small molecule SP140 inhibitor (GSK761) and utilize this to elucidate SP140 function in macrophages. We show that SP140 is highly expressed in CD mucosal macrophages and in in vitro-generated inflammatory macrophages. SP140 inhibition through GSK761 reduced monocyte-to-inflammatory macrophage differentiation and lipopolysaccharide (LPS)-induced inflammatory activation, while inducing the generation of CD206+ regulatory macrophages that were shown to associate with a therapeutic response to anti-TNF in CD patients. SP140 preferentially occupies transcriptional start sites in inflammatory macrophages, with enrichment at gene loci encoding pro-inflammatory cytokines/chemokines and inflammatory pathways. GSK761 specifically reduces SP140 chromatin binding and thereby expression of SP140-regulated genes. GSK761 inhibits the expression of cytokines, including TNF, by CD14+ macrophages isolated from CD intestinal mucosa. Conclusions: This study identifies SP140 as a druggable epigenetic therapeutic target for CD