Uncertainties in stellar structure and evolution theory are largest for stars undergoing core convection on the main sequence. A powerful way to calibrate the free parameters used in the theory of ...stellar interiors is asteroseismology, which provides direct measurements of angular momentum and element transport. We report the detection and classification of new variable O and B stars using high-precision short-cadence (2 minutes) photometric observations assembled by the Transiting Exoplanet Survey Satellite (TESS). In our sample of 154 O and B stars, we detect a high percentage (90%) of variability. Among these we find 23 multiperiodic pulsators, 6 eclipsing binaries, 21 rotational variables, and 25 stars with stochastic low-frequency variability. Several additional variables overlap between these categories. Our study of O and B stars not only demonstrates the high data quality achieved by TESS for optimal studies of the variability of the most massive stars in the universe, but also represents the first step toward the selection and composition of a large sample of O and B pulsators with high potential for joint asteroseismic and spectroscopic modeling of their interior structure with unprecedented precision.
Global longitudinal strain (GLS) is reported to be more reproducible and prognostic than ejection fraction. Automated, transparent methods may increase trust and uptake.
The authors developed open ...machine-learning–based GLS methodology and validate it using multiexpert consensus from the Unity UK Echocardiography AI Collaborative.
We trained a multi-image neural network (Unity-GLS) to identify annulus, apex, and endocardial curve on 6,819 apical 4-, 2-, and 3-chamber images. The external validation dataset comprised those 3 views from 100 echocardiograms. End-systolic and -diastolic frames were each labelled by 11 experts to form consensus tracings and points. They also ordered the echocardiograms by visual grading of longitudinal function. One expert calculated global strain using 2 proprietary packages.
The median GLS, averaged across the 11 individual experts, was −16.1 (IQR: −19.3 to −12.5). Using each case’s expert consensus measurement as the reference standard, individual expert measurements had a median absolute error of 2.00 GLS units. In comparison, the errors of the machine methods were: Unity-GLS 1.3, proprietary A 2.5, proprietary B 2.2. The correlations with the expert consensus values were for individual experts 0.85, Unity-GLS 0.91, proprietary A 0.73, proprietary B 0.79. Using the multiexpert visual ranking as the reference, individual expert strain measurements found a median rank correlation of 0.72, Unity-GLS 0.77, proprietary A 0.70, and proprietary B 0.74.
Our open-source approach to calculating GLS agrees with experts’ consensus as strongly as the individual expert measurements and proprietary machine solutions. The training data, code, and trained networks are freely available online.
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ABSTRACT
Objective
In light of the ongoing opioid crisis, Naval Medical Center Portsmouth (NMCP) created the Long-Term Opioid Therapy Safety (LOTS) program to reduce risks and improve long-term ...opioid therapy outcomes. Our primary outcome was change in compliance with the recommended safety metrics.
Design
This is a retrospective cohort study performed at NMCP, a large military academic medical center providing comprehensive medical care to DoD beneficiaries. The NMCP LOTS program provides both patient and provider narcotic education as well as medical record auditing. The NMCP LOTS program promotes adherence to published CDC, the DVA, and DoD guidelines.
Methods
Anonymized data were compiled each fiscal quarter and were analyzed retrospectively. Adult patients prescribed opioids for at least 90 days without a gap of 30 days between prescriptions were included in this study. The investigators recorded and reported provider compliance with LOTS metrics over the same period.
Results
Compliance with the recommended safety metrics improved. We noted a decrease in the number of long-term opioid patients, concurrent benzodiazepine prescriptions, and patients prescribed greater than 90 morphine equivalents per day during the observation period. The number of naloxone prescriptions for LOTS patients also increased, reflecting improved guideline adherence.
Conclusion
Systematic education and feedback to providers are effective in creating a system and culture of opioid reduction, safe opioid prescribing, and system accountability. This article presents a comprehensive approach to modifying prescribing patterns of long-term opioids in a large healthcare system.
BACKGROUND
Passive therapy with convalescent plasma provides an early opportunity to intervene in Ebola virus disease (EVD). Methods for field screening and selection of potential donors and ...quantifying plasma antibody are needed.
STUDY DESIGN AND METHODS
Recombinant Ebola virus glycoprotein (EBOV GP) was formatted into immunoglobulin G‐capture, competitive, and double‐antigen bridging enzyme immunoassays (EIAs). EVD survivors in Freetown, Sierra Leone, were recruited as potential plasma donors and assessed locally using sera alone and/or paired sera and oral fluids (ORFs). Uninfected controls comprised unexposed Gambians and communities in Western Area, Sierra Leone. Antibody neutralization in selected sera was measured retrospectively in a pseudotype virus assay.
RESULTS
A total of 115 potential donors were considered for enrollment: 110 plasma samples were concordantly reactive in the three EIAs; three were concordantly unreactive and two were reactive in two of three EIAs (98.2% agreement; 95% confidence interval CI, 93.9%‐99.8%). In 88 donors with paired ORF and plasma, G‐capture EIA reactivity correlated well in the two analytes (R2 = 0.795). Plasma and ORF from 44 Gambians were unreactive. ORF samples from 338 of 339 unexposed Western Area community controls were unreactive (specificity, 99.7%; 95% CI, 98.4%‐99.7%); ORF samples from 113 of 116 Kerry Town EVD survivors were reactive (sensitivity, 97.4%; 95% CI, 92.5%‐99.5%). Strong reactivity in G‐capture and/or competitive EIAs identified donors with high plasma EBOV GP antibody levels in the double‐antigen bridging assay, correlating with high levels of neutralizing antibody.
CONCLUSIONS
In‐field testing can qualify convalescent donors for providing high‐titer antibody.
Abstract
Glucocorticoids have multiple therapeutic benefits and are used both for immunosuppression and treatment purposes. Notwithstanding their benefits, glucocorticoid use often leads to ...hyperglycemia. Owing to the pathophysiologic overlap in glucocorticoid-induced hyperglycemia (GIH) and type 2 diabetes (T2D), we hypothesized that genetic variation in glucocorticoid pathways contributes to T2D risk. To determine the genetic contribution of glucocorticoid action on T2D risk, we conducted multiple genetic studies. First, we performed gene-set enrichment analyses on 3 collated glucocorticoid-related gene sets using publicly available genome-wide association and whole-exome data and demonstrated that genetic variants in glucocorticoid-related genes are associated with T2D and related glycemic traits. To identify which genes are driving this association, we performed gene burden tests using whole-exome sequence data. We identified 20 genes within the glucocorticoid-related gene sets that are nominally enriched for T2D-associated protein-coding variants. The most significant association was found in coding variants in coiled-coil α-helical rod protein 1 (CCHCR1) in the HLA region (P = .001). Further analyses revealed that noncoding variants near CCHCR1 are also associated with T2D at genome-wide significance (P = 7.70 × 10–14), independent of type 1 diabetes HLA risk. Finally, gene expression and colocalization analyses demonstrate that variants associated with increased T2D risk are also associated with decreased expression of CCHCR1 in multiple tissues, implicating this gene as a potential effector transcript at this locus. Our discovery of a genetic link between glucocorticoids and T2D findings support the hypothesis that T2D and GIH may have shared underlying mechanisms.
Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies
. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined ...set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013-2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a 'decay-stimulation-decay' pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77-100 days and a doubling time of 46-86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5-2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.
A new one-pot synthesis of cationic N-heterocyclic carbene (NHC) complexes of rhodium and iridium from neat dialkyl-imidazolium ionic liquids (ILs) in the absence of external bases, leaves pure, ...catalytically active IL solutions faster, cleaner and more efficient than traditional syntheses of such NHC complexes.
A direct synthetic route to cationic N-heterocyclic carbene (NHC) complexes of rhodium and iridium from neat dialkyl-imidazolium ionic liquids (ILs) has been found. The method uses complexes bearing basic anionic ligands, M(COD)(PPh
3)X, X
=
OEt, MeCO
2, which react with the inactivated imidazolium cation in the absence of external bases yielding one M-NHC moiety and the free protonated base. This new one-pot synthesis leaving pure, catalytically active IL solutions is faster, cleaner and more efficient than traditional syntheses of such NHC complexes. The observed reactivity also gives insight into NHC incorporation of rhodium and iridium catalyzed reactions performed in common dialkyl-imidazolium ILs.
The complexes synthesised in this manner are compared with their bis-phosphine analogues in terms of activity for catalytic dehydrogenation of 1,5-cyclooctadiene and 1,3-cyclooctadiene in neat BMIMNTf
2 as solvent. Even at high temperature, no ligand exchange reaction is observed with (COD)M(PPh
3)
2 NTf
2 catalysts. As expected, the yields of all the reactions were low, iridium was much more active in C–H activation than rhodium and the NHC ligands were more stable than triphenylphosphine. For all catalysts, the isomerisation of 1,5-cyclooctadiene is the major reaction. However, the phosphine-NHC complex of iridium seems to be more selective for dehydrogenation than its bis-phosphine counterpart, which is more active in transfer-hydrogenation and less stable under the applied conditions. Different reaction conditions were tried in order to optimise selectivity for dehydrogenation over isomerisation and transfer-hydrogenation. Surprisingly, with 1,3-cyclooctadiene as substrate selectivity for dehydrogenation is much higher than with 1,5-cyclooctadiene for all catalysts.
Two processes are described for improving reaction rates for relatively hydrophobic substrates in aqueous biphasic systems. In the first, 1-octyl-3-methylimidazolium bromide (OctmimBr) increases the ...rate of hydroformylation of 1-octene from 8% conversion in 24 h to full conversion of 1.5 h. Phase separation is fast and catalyst retention is good. 1-Hexyl-3-methylimidazolium bromide gives little rate enhancement, whilst 1-decyl-3-methylimidazolium bromide gives stable emulsions., The mechanism of action of these additives is discussed. In the second approach, functionalising PPh
3
with amidine groups allows the rhodium catalysed hydroformylation of 1-octene in toluene with a very high reaction rate. The catalyst can be switched between toluene and water by bubbling CO
2
and back into toluene by bubbling N
2
at 60 °C. This switching has been used to separate the catalyst from hydrophobic (from 1-octene) or hydrophilic (from allyl alcohol) aldehydes obtained from hydroformylation reactions. CO
2
expanded liquids have been shown to be effective media for transporting substrates and catalysts over supported ionic liquid phase (SILP) catalysts. The advantages offered over all gas phase and liquid phase catalysts are discussed.
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