Multi-epoch radial velocity measurements of stars can be used to identify stellar, substellar, and planetary-mass companions. Even a small number of observation epochs can be informative about ...companions, though there can be multiple qualitatively different orbital solutions that fit the data. We have custom-built a Monte Carlo sampler (The Joker) that delivers reliable (and often highly multimodal) posterior samplings for companion orbital parameters given sparse radial velocity data. Here we use The Joker to perform a search for companions to 96,231 red giant stars observed in the APOGEE survey (DR14) with ≥3 spectroscopic epochs. We select stars with probable companions by making a cut on our posterior belief about the amplitude of the variation in stellar radial velocity induced by the orbit. We provide (1) a catalog of 320 companions for which the stellar companion's properties can be confidently determined, (2) a catalog of 4898 stars that likely have companions, but would require more observations to uniquely determine the orbital properties, and (3) posterior samplings for the full orbital parameters for all stars in the parent sample. We show the characteristics of systems with confidently determined companion properties and highlight interesting systems with candidate compact object companions.
We present a model for the interaction of the GD-1 stellar stream with a massive perturber that naturally explains many of the observed stream features, including a gap and an off-stream spur of ...stars. The model involves an impulse by a fast encounter, after which the stream grows a loop of stars at different orbital energies. At specific viewing angles, this loop appears offset from the stream track. A quantitative comparison of the spur-and-gap features prefers models where the perturber is in the mass range of 106-108 M . Orbit integrations back in time show that the stream encounter could not have been caused by any known globular cluster or dwarf galaxy with a determined orbit, and mass, size, and impact parameter arguments show that it could not have been caused by a molecular cloud in the Milky Way disk. The most plausible explanation for the gap-and-spur structure is an encounter with a dark matter substructure, like those predicted to populate galactic halos in ΛCDM cosmology. However, the expected densities of ΛCDM subhalos in this mass range and in this part of the Milky Way are 2 -3 lower than the inferred density of the GD-1 perturber. This observation opens up the possibility that detailed observations of streams could measure the mass spectrum of dark matter substructures and even identify individual substructures and their orbits in the Galactic halo.
Abstract Objectives To present estimates of clinically meaningful or minimal important changes for the Oxford Hip Score (OHS) and the Oxford Knee Score (OKS) after joint replacement surgery. Study ...Design and Setting Secondary data analysis of the NHS patient-reported outcome measures data set that included 82,415 patients listed for hip replacement surgery and 94,015 patients listed for knee replacement surgery was performed. Results Anchor-based methods revealed that meaningful change indices at the group level minimal important change (MIC), for example in cohort studies, were ∼11 points for the OHS and ∼9 points for the OKS. For assessment of individual patients, receiver operating characteristic analysis produced MICs of 8 and 7 points for OHS and OKS, respectively. Additionally, the between group minimal important difference (MID), which allows the estimation of a clinically relevant difference in change scores from baseline when comparing two groups, that is, for clinical trials, was estimated to be ∼5 points for both the OKS and the OHS. The distribution-based minimal detectable change (MDC90 ) estimates for the OKS and OHS were 4 and 5 points, respectively. Conclusion This study has produced and discussed estimates of minimal important change/difference for the OKS/OHS. These estimates should be used in the power calculations and the interpretation of studies using the OKS and OHS. The MDC90 (∼4 points OKS and ∼5 points OHS) represents the smallest possible detectable change for each of these instruments, thus indicating that any lower value would fall within measurement error.
Summary Background Health-care workers have been implicated in nosocomial outbreaks of Staphylococcus aureus , but the dearth of evidence from non-outbreak situations means that routine health-care ...worker screening and S aureus eradication are controversial. We aimed to determine how often S aureus is transmitted from health-care workers or the environment to patients in an intensive care unit (ICU) and a high-dependency unit (HDU) where standard infection control measures were in place. Methods In this longitudinal cohort study, we systematically sampled health-care workers, the environment, and patients over 14 months at the ICU and HDU of the Royal Sussex County Hospital, Brighton, England. Nasal swabs were taken from health-care workers every 4 weeks, bed spaces were sampled monthly, and screening swabs were obtained from patients at admission to the ICU or HDU, weekly thereafter, and at discharge. Isolates were cultured and their whole genome sequenced, and we used the threshold of 40 single-nucleotide variants (SNVs) or fewer to define subtypes and infer recent transmission. Findings Between Oct 31, 2011, and Dec 23, 2012, we sampled 198 health-care workers, 40 environmental locations, and 1854 patients; 1819 isolates were sequenced. Median nasal carriage rate of S aureus in health-care workers at 4-weekly timepoints was 36·9% (IQR 35·7–37·3), and 115 (58%) health-care workers had S aureus detected at least once during the study. S aureus was identified in 8–50% of environmental samples. 605 genetically distinct subtypes were identified (median SNV difference 273, IQR 162–399) at a rate of 38 (IQR 34–42) per 4-weekly cycle. Only 25 instances of transmission to patients (seven from health-care workers, two from the environment, and 16 from other patients) were detected. Interpretation In the presence of standard infection control measures, health-care workers were infrequently sources of transmission to patients. S aureus epidemiology in the ICU and HDU is characterised by continuous ingress of distinct subtypes rather than transmission of genetically related strains. Funding UK Medical Research Council, Wellcome Trust, Biotechnology and Biological Sciences Research Council, UK National Institute for Health Research, and Public Health England.
We report and discuss the discovery of a significant difference in the chemical abundances of a comoving pair of bright solar-type stars, HD 240430 and HD 240429. The two stars have an estimated 3D ...separation of 0.6 pc ( 0.01 pc projected) at a distance of r 100 pc with nearly identical 3D velocities, as inferred from Gaia TGAS parallaxes and proper motions, and high-precision radial velocity measurements. Stellar parameters determined from high-resolution spectra obtained with the High Resolution Echelle Spectrometer (HIRES) at the Keck Observatory indicate that the two stars are ∼4 Gyr old. The more metal-rich of the two, HD 240430, shows an enhancement of refractory ( K) elements by 0.2 dex and a marginal enhancement of (moderately) volatile elements ( K; , , , , and ). This is the largest metallicity difference found in a wide binary pair to date. Additionally, HD 240430 shows an anomalously high surface lithium abundance ( ), higher than its cooler companion by 0.5 dex. The proximity in phase-space and ages between the two stars suggests that they formed together with the same composition, which is at odds with the observed differences in metallicity and abundance patterns. We therefore suggest that the star HD 240430, "Kronos," accreted of rocky material after birth, selectively enhancing the refractory elements as well as lithium in its surface and convective envelope.
The primary sample of the Gaia Data Release 1 is the Tycho-Gaia Astrometric Solution (TGAS): 2 million Tycho-2 sources with improved parallaxes and proper motions relative to the initial catalog. ...This increased astrometric precision presents an opportunity to find new binary stars and moving groups. We search for high-confidence comoving pairs of stars in TGAS by identifying pairs of stars consistent with having the same 3D velocity using a marginalized likelihood ratio test to discriminate candidate comoving pairs from the field population. Although we perform some visualizations using (bias-corrected) inverse parallax as a point estimate of distance, the likelihood ratio is computed with a probabilistic model that includes the covariances of parallax and proper motions and marginalizes the (unknown) true distances and 3D velocities of the stars. We find 13,085 comoving star pairs among 10,606 unique stars with separations as large as 10 pc (our search limit). Some of these pairs form larger groups through mutual comoving neighbors: many of these pair networks correspond to known open clusters and OB associations, but we also report the discovery of several new comoving groups. Most surprisingly, we find a large number of very wide ( pc) separation comoving star pairs, the number of which increases with increasing separation and cannot be explained purely by false-positive contamination. Our key result is a catalog of high-confidence comoving pairs of stars in TGAS. We discuss the utility of this catalog for making dynamical inferences about the Galaxy, testing stellar atmosphere models, and validating chemical abundance measurements.
Continuing professional development aims to provide health professionals with the knowledge, skills, and competencies needed to improve care. Physicians and other clinicians increasingly practice ...within complex health care delivery organizations aiming to improve the care of populations of patients with multiple problems and differing needs. These organizations are composed of local units in different departments and venues; these teams and the patients they care for change over time. Improving outcomes within constantly changing complex organizations delivering population care takes time and persistence. It takes time to equip critical masses of clinicians and other personnel with knowledge and skills to effect change. Although some changes might be simple, those involving new workflows require implementation support. Not all change will be smooth; individuals need opportunities to learn from and adjust their early intervention efforts, measure effectiveness of change, and sustain successful practices. Longitudinal support is necessary to affect change over complex organizations. This essay proposes that to be more supportive and valuable to health care delivery organizations, continuing professional development needs to intentionally participate in longitudinal, collaborative, context-specific, team-based interventions. An expanded menu of evaluation approaches will better describe the role of continuing professional development in helping health care professionals and organizations address increasingly complex health care delivery problems and improve patient and population outcomes. Selected concepts to achieve these ends are introduced at a high level in this article. Readers are invited to explore concepts that resonate with their current situation in further detail.
Theoretical models of stellar evolution predict that most of the lithium inside a star is destroyed as the star becomes a red giant. However, observations reveal that about 1% of red giants are ...peculiarly rich in lithium, often exceeding the amount in the interstellar medium or predicted from the big bang. With only about 150 lithium-rich giants discovered in the past four decades, and no distinguishing properties other than lithium enhancement, the origin of lithium-rich giant stars is one of the oldest problems in stellar astrophysics. Here we report the discovery of 2330 low-mass (1-3 M ) lithium-rich giant stars, which we argue are consistent with internal lithium production that is driven by tidal spin-up by a binary companion. Our sample reveals that most lithium-rich giants have helium-burning cores ( ), and that the frequency of lithium-rich giants rises with increasing stellar metallicity. We find that while planet accretion may explain some lithium-rich giants, it cannot account for the majority that have helium-burning cores. We rule out most other proposed explanations for the origin of lithium-rich giants. Our analysis shows that giants remain lithium-rich for only about two million years. A prediction from this lithium depletion timescale is that most lithium-rich giants with a helium-burning core have a binary companion.
Peptide agonists of the glucagon-like peptide-1 receptor (GLP-1R) have revolutionized diabetes therapy, but their use has been limited because they require injection. Herein, we describe the ...discovery of the orally bioavailable, small-molecule, GLP-1R agonist PF-06882961 (danuglipron). A sensitized high-throughput screen was used to identify 5-fluoropyrimidine-based GLP-1R agonists that were optimized to promote endogenous GLP-1R signaling with nanomolar potency. Incorporation of a carboxylic acid moiety provided considerable GLP-1R potency gains with improved off-target pharmacology and reduced metabolic clearance, ultimately resulting in the identification of danuglipron. Danuglipron increased insulin levels in primates but not rodents, which was explained by receptor mutagensis studies and a cryogenic electron microscope structure that revealed a binding pocket requiring a primate-specific tryptophan 33 residue. Oral administration of danuglipron to healthy humans produced dose-proportional increases in systemic exposure (NCT03309241). This opens an opportunity for oral small-molecule therapies that target the well-validated GLP-1R for metabolic health.
The potential for machine learning (ML) to enhance the efficiency of medical specialty boards has not been explored. We applied unsupervised ML to identify archetypes among American Board of Family ...Medicine (ABFM) Diplomates regarding their practice characteristics and motivations for participating in continuing certification, then examined associations between motivation patterns and key recertification outcomes.
Diplomates responding to the 2017 to 2021 ABFM Family Medicine continuing certification examination surveys selected motivations for choosing to continue certification. We used Chi-squared tests to examine difference proportions of Diplomates failing their first recertification examination attempt who endorsed different motivations for maintaining certification. Unsupervised ML techniques were applied to generate clusters of physicians with similar practice characteristics and motivations for recertifying. Controlling for physician demographic variables, we used logistic regression to examine the effect of motivation clusters on recertification examination success and validated the ML clusters by comparison with a previously created classification schema developed by experts.
ML clusters largely recapitulated the intrinsic/extrinsic framework devised by experts previously. However, the identified clusters achieved a more equal partitioning of Diplomates into homogenous groups. In both ML and human clusters, physicians with mainly extrinsic or mixed motivations had lower rates of examination failure than those who were intrinsically motivated.
This study demonstrates the feasibility of using ML to supplement and enhance human interpretation of board certification data. We discuss implications of this demonstration study for the interaction between specialty boards and physician Diplomates.
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