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The radius valley, i.e. a dearth of planets with radii between 1.5 and 2 Earth radii, provides insights into planetary formation and evolution. Using homogenously revised planetary parameters from Kepler 1-min short cadence light curves, we remodel transits of 72 small planets mostly orbiting low-mass stars, improving the precision and accuracy of planet parameters. By combining this sample with a similar sample of planets around higher mass stars, we determine the depth of the radius valley as a function of stellar mass. We find that the radius valley is shallower for low-mass stars compared to their higher mass counterparts. Upon comparison, we find that theoretical models of photoevaporation underpredict the number of planets observed inside the radius valley for low-mass stars: with decreasing stellar mass, the predicted fraction of planets inside the valley remains approximately constant whereas the observed fraction increases. We argue that this provides evidence for the presence of icy planets around low-mass stars. Alternatively, planets orbiting low-mass stars undergo more frequent collisions and scatter in the stars' high-energy output may also cause planets to fill the valley. We predict that more precise mass measurements for planets orbiting low-mass stars would be able to distinguish between these scenarios. [ABSTRACT FROM AUTHOR]

Baseline information about declining North American shorebird populations is essential to determine the effects of global warming at low-lying coastal areas of the Arctic and subarctic, where numerous taxa breed, and to assess population recovery throughout their range. We estimated population sizes on the Yukon–Kuskokwim Delta (YKD) in western Alaska on the eastern edge of the Bering Sea. We conducted ground-based surveys during 2015 and 2016 at 589 randomly selected plots from an area of 35,769 km2. We used stratified random sampling in 8 physiographic strata and corrected population estimates using detection ratios derived from double sampling on a subset of plots. We detected 11,110 breeding individuals of 21 taxa. Western Sandpiper (Calidris mauri), Red-necked Phalarope (Phalaropus lobatus), Dunlin (subspecies C. alpina pacifica), and Wilson's Snipe (Gallinago delicata) were the most abundant taxa. We estimated that ~7 million individual shorebirds were breeding on the entire YKD in 2015 and 2016. Our surveys of this region provided robust population estimates (coefficient of variations ≤ 0.35) for 14 species. Our results indicate that the YKD supports a large proportion of North America's breeding populations of the Pacific Golden-Plover (Pluvialis fulva), the western population of a Whimbrel subspecies (Numenius phaeopus hudsonicus), a Bar-tailed Godwit subspecies (Limosa lapponica baueri), Black Turnstone (Arenaria melanocephala), a Dunlin subspecies (C. alpina pacifica), and Western Sandpiper. Our study highlights the importance of breeding shorebirds of this relatively pristine but climatically sensitive deltaic system. Estuaries and deltaic systems worldwide are rapidly being degraded by anthropogenic activities. Our population estimates can be used to refine prior North American population estimates, determine the effects of global warming, and evaluate conservation success by measuring population change over time. [ABSTRACT FROM AUTHOR]

The atmospheres of small, close-in exoplanets are vulnerable to rapid mass loss during protoplanetary disc dispersal via a process referred to as 'boil-off', in which confining pressure from the local gas disc reduces, inducing atmospheric loss and contraction. We construct self-consistent models of planet evolution during gaseous core accretion and boil-off. As the surrounding disc gas dissipates, we find that planets lose mass via subsonic breeze outflows which allow causal contact to exist between disc and planet. Planets initially accrete of order |$\sim 10~{{\ \rm per\ cent}}$| in atmospheric mass, however, boil-off can remove |$\gtrsim 90~{{\ \rm per\ cent}}$| of this mass during disc dispersal. We show that a planet's final atmospheric mass fraction is strongly dictated by the ratio of cooling time-scale to disc dispersal time-scale, as well as the planet's core mass and equilibrium temperature. With contributions from core cooling and radioactivity, we show that core luminosity eventually leads to the transition from boil-off to core-powered mass loss. We find that smaller mass planets closest to their host star may have their atmospheres completely stripped through a combination of boil-off and core-powered mass loss during disc dispersal, implying the existence of a population-level radius gap emerging as the disc disperses. We additionally consider the transition from boil-off/core-powered mass loss to X-ray and extreme ultraviolet (XUV) photoevaporation by considering the penetration of stellar XUV photons below the planet's sonic surface. Finally, we show that planets may open gaps in their protoplanetary discs during the late stages of boil-off, which may enhance mass-loss rates. [ABSTRACT FROM AUTHOR]

Bright galaxies at submillimetre wavelengths from Herschel are now well known to be predominantly strongly gravitationally lensed. The same models that successfully predicted this strongly lensed population also predict about 1 per cent of faint 450 μm-selected galaxies from deep James Clerk Maxwell Telescope (JCMT) surveys will also be strongly lensed. Follow-up ALMA campaigns have so far found one potential lens candidate, but without clear compelling evidence, for example, from lensing arcs. Here, we report the discovery of a compelling gravitational lens system confirming the lensing population predictions, with a z s = 3.4 ± 0.4 submm source lensed by a z spec = 0.360 foreground galaxy within the COSMOS field, identified through public JWST imaging of a 450 μm source in the SCUBA-2 Ultra Deep Imaging EAO Survey (STUDIES) catalogue. These systems will typically be well within the detectable range of future wide-field surveys such as Euclid and Roman , and since submillimetre galaxies are predominantly very red at optical/near-infrared wavelengths, they will tend to appear in near-infrared channels only. Extrapolating to the Euclid -Wide survey, we predict tens of thousands of strongly lensed near-infrared galaxies. This will be transformative for the study of dusty star-forming galaxies at cosmic noon, but will be a contaminant population in searches for strongly lensed ultra-high-redshift galaxies in Euclid and Roman. [ABSTRACT FROM AUTHOR]

We prove that the bi-invariant Einstein metric on |$SU_{2n+1}$| is isolated in the moduli space of Einstein metrics, even though it admits infinitesimal deformations. This gives a non-Kähler, non-product example of this phenomenon adding to the famous example of |$\mathbb{C}\mathbb{P}^{2n}\times \mathbb{C}\mathbb{P}^{1}$| found by Koiso. We apply our methods to derive similar solitonic rigidity results for the Kähler–Einstein metrics on "odd" Grassmannians. We also make explicit a connection between non-integrable deformations and the dynamical instability of metrics under Ricci flow. [ABSTRACT FROM AUTHOR]

Purpose To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2024 in the United States, with a focus on the nonfederal hospital and clinic sectors. Methods Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2024 were reviewed—including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, endocrine drugs, generics, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2024 were based on a combination of quantitative analyses and expert opinion. Results In 2023, overall pharmaceutical expenditures in the US grew 13.6% compared to 2022, for a total of $722.5 billion. Utilization (a 6.5% increase), new drugs (a 4.2% increase) and price (a 2.9% increase) drove this increase. Semaglutide was the top drug in 2023, followed by adalimumab and apixaban. Drug expenditures were $37.1 billion (a 1.1% decrease) and $135.7 billion (a 15.0% increase) in nonfederal hospitals and clinics, respectively. In clinics, increased utilization drove growth, with a small impact from price and new products. In nonfederal hospitals, a drop in utilization led the decrease in expenditures, with price and new drugs modestly contributing to growth in spending. Several new drugs that will influence spending are expected to be approved in 2024. Specialty, endocrine, and cancer drugs will continue to drive expenditures. Conclusion For 2024, we expect overall prescription drug spending to rise by 10.0% to 12.0%, whereas in clinics and hospitals we anticipate an 11.0% to 13.0% increase and a 0% to 2.0% increase, respectively, compared to 2023. These national estimates of future pharmaceutical expenditure growth may not be representative of any health system because of the myriad of local factors that influence actual spending. [ABSTRACT FROM AUTHOR]

Purpose Ensuring pharmacy technicians are adequately trained and prepared to enter the workforce is an important first step in addressing technician staff shortages. How pharmacy technician learners perceive their experiences after completion of a training program remains unknown. This study evaluated participant outcomes and self-efficacy ratings for common technician competencies after completion of a pharmacy technician training program. Methods Between December 2021 and March 2023, we distributed a survey to participants who successfully completed the program approximately 3 months after their estimated completion date. The survey assessed 6 domains: enrollment and academic progression, utilization of educational resources, self-perceived proficiency on core competencies of a pharmacy technician, employment information, program recommendations, and student demographics. Results Thirty-six participants completed the survey, corresponding to a 60% response rate. Participants were attracted to the pharmacy technician program due to its affiliation with a college of pharmacy, online format, and affordability. Half of respondents were actively employed as pharmacy technicians, and the self-reported certification exam passage rate slightly exceeded national averages (78% vs 70% to 71%). Participants' self-efficacy ratings for pharmacy technician competencies were high (mean rating of 4.12 out of 5). Overwhelmingly, 97% of participants agreed that the program prepared them well for becoming a pharmacy technician. Conclusion A pharmacy technician training program housed within a college of pharmacy presents one potential solution in addressing pharmacy technician workforce shortages. Participants positively viewed their training experience, with high self-efficacy ratings for pharmacy technician competencies. Moreover, national certification exam results were slightly better than national averages. [ABSTRACT FROM AUTHOR]

The relativistic outflows that produce long gamma-ray bursts (LGRBs) can be described by a structured jet model where prompt |$\gamma$| -ray emission is restricted to a narrow region in the jet's core. Viewing the jet off-axis from the core, a population of afterglows without an associated GRB detection can be predicted. In this work, we conduct an archival search for these 'orphan' afterglows (OAs) with minute-cadence, deep (⁠|$g\sim 23$|⁠) data from the Dark Energy Camera (DECam) taken as part of the Deeper, Wider, Faster programme (DWF). We introduce a method to select fast-evolving OA candidates within DWF data that comprises a machine learning model, based on a realistic synthetic population of OAs. Using this classifier, we recover 51 OA candidates. Of these candidates, 42 are likely flare events from M-class stars. The remaining nine possess quiescent, coincident sources in archival data with angular profiles consistent with a star and are inconsistent with the expected population of LGRB host galaxies. We therefore conclude that these are likely Galactic events. We calculate an upper limit on the rate of OAs down to |$g\lt 22$| AB mag of 7.46 deg |$^{-2}$| yr |$^{-1}$| using our criteria and constrain possible jet structures. We also place an upper limit of the characteristic angle between the |$\gamma$| -ray-emitting region and the jet's half-opening angle. For a smooth power law and a power law with core jet model, respectively, these values are |$58.3^{\circ }$| and |$56.6^{\circ }$|⁠ , for a power-law index of 0.8 and |$75.3^{\circ }$| and |$76.8^{\circ }$| for a power-law index of 1.2. [ABSTRACT FROM AUTHOR]

The theory describing the evolution of offspring size often assumes that the production cost per unit volume is the same for small and large offspring. However, this may not be true if indirect costs of reproduction (e.g. material and energetic costs of supporting offspring development) scale disproportionately with offspring size. Here we show how direct and indirect costs of reproduction can be explicitly modeled within the Smith–Fretwell framework and how observations of size-number relationships can thus be used to evaluate indirect costs. We applied this analysis to measures of egg volume and fecundity for over 300 individuals of a coastal fish species and found that the tradeoff was much stronger than the expected inverse (fecundity scaled with volume−1.843). Larger offspring were thus more expensive to produce. For our study species, an important indirect cost was that larger eggs were accompanied by disproportionately more ovarian fluid. Calorimetry and removal experiments were used to further measure both the energetic costs and fitness benefits of ovarian fluid. In addition, we show that indirect costs of reproduction can intensify size-number tradeoffs in a variety of fishes. Indirect costs of reproduction can be large and may therefore play an important role in the evolution of offspring size. [ABSTRACT FROM AUTHOR]

Evolutionary theory predicts that the accumulation of deleterious mutations in asexually reproducing organisms should lead to genomic decay. Clonally reproducing cell lines, i.e. transmissible cancers, when cells are transmitted as allografts/xenografts, break these rules and survive for centuries and millennia. The currently known 11 transmissible cancer lineages occur in dogs (canine venereal tumour disease), in Tasmanian devils (devil facial tumor diseases, DFT1 and DFT2), and in bivalves (bivalve transmissible neoplasia). Despite the mutation loads of these cell lines being much higher than observed in human cancers, they have not been eliminated in space and time. Here, we provide potential explanations for how these fascinating cell lines may have overcome the fitness decline due to the progressive accumulation of deleterious mutations and propose that the high mutation load may carry an indirect positive fitness outcome. We offer ideas on how these host–pathogen systems could be used to answer outstanding questions in evolutionary biology. The recent studies on the evolution of these clonal pathogens reveal key mechanistic insight into transmissible cancer genomes, information that is essential for future studies investigating how these contagious cancer cell lines can repeatedly evade immune recognition, evolve, and survive in the landscape of highly diverse hosts. [ABSTRACT FROM AUTHOR]

Background Although genome-wide association studies (GWAS) of breast cancer (BC) identified common variants which differ between intrinsic subtypes, genes through which these variants act to impact BC risk have not been fully established. Transcriptome-wide association studies (TWAS) have identified genes associated with overall BC risk, but subtype-specific differences are largely unknown. Methods We performed two multi-tissue TWAS for each BC intrinsic subtype, including an expression-based approach that collated TWAS signals from expression quantitative trait loci (eQTLs) across multiple tissues and a novel splicing-based approach that collated signals from splicing QTLs (sQTLs) across intron clusters and subsequently across tissues. We used summary statistics for five intrinsic subtypes including Luminal A-like, Luminal B-like, Luminal B/HER2-negative-like, HER2-enriched-like, and triple-negative BC, generated from 106 278 BC cases and 91 477 controls in the Breast Cancer Association Consortium. Results Overall, we identified 235 genes in 88 loci that were associated with at least one of the five intrinsic subtypes. Most genes were subtype-specific, and many have not been reported in previous TWAS. We discovered common variants that modulate expression of CHEK2 confer increased risk to Luminal A-like BC, in contrast to the viewpoint that CHEK2 primarily harbors rare, penetrant mutations. Additionally, our splicing-based TWAS provided population-level support for MDM4 splice variants that increased the risk of triple-negative BC. Conclusion Our comprehensive, multi-tissue TWAS corroborated previous GWAS loci for overall BC risk and intrinsic subtypes, while underscoring how common variation that impacts expression and splicing of genes in multiple tissue types can be used to further elucidate the etiology of BC. [ABSTRACT FROM AUTHOR]

Introduction There are limited data regarding the international travel history and preparation, as well as glycaemic control practices, risk behaviours and experiences of people with type 1 diabetes during travel. Our review aimed to address the research question: 'What are the health practices, behaviours and experiences of people with type 1 diabetes when travelling?' Methods We conducted a mixed-methods narrative review using adapted review methods from the Centre for Reviews and Dissemination and standards developed by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. MEDLINE, Scopus, PubMed and CINAHL, and the reference lists of all eligible studies were searched. Results Nine records comprising of 11 studies were included, with data heralding from various countries, published between 1990 and 2022. We identified three main themes: travel preparation (type of travel, planning and advice seeking); issues related to air travel (airports and airport security, hypoglycaemia and hyperglycaemia, and insulin) and general travel-related issues (illness and medical treatment, type 1 diabetes management, and major concerns and barriers). Conclusions Our findings highlighted the lack of quality data regarding type 1 diabetes and travel within the extant literature, as well a pressing need for empirical studies to be undertaken and consensus guidelines developed to improve the travel experiences of people with type 1 diabetes. Unless change is made, people with type 1 diabetes will continue to experience preventable risk and harm while travelling. [ABSTRACT FROM AUTHOR]

Accepted by: Aris Syntetos This paper examines the impact of temporary supply chain disruptions in a general equilibrium model with multiple stages of production for capital goods and a flexible time-to-build structure. Production disruptions at one or more stages result in declines in overall shipments and increases in the ratios of unfilled orders and work-in-process inventories to shipments. The model is calibrated to industries in durable goods manufacturing during the Covid-19 pandemic, and is shown to generate realistic dynamic responses to temporary production disruptions. Consistent with the data, an unanticipated 1-month disruption to upstream production results in a decline in shipments and an increase in the ratio of unfilled orders to shipments lasting more than 6 months. [ABSTRACT FROM AUTHOR]

The distribution of mass in galaxy-scale strong gravitational lenses is often modelled as an elliptical power-law plus 'external shear', which notionally accounts for neighbouring galaxies and cosmic shear along our line of sight. A small amount of external shear could come from these sources, but we show that the vast majority does not. Except in a handful of rare systems, the best-fitting values do not correlate with independent measurements of line-of-sight shear: from weak lensing in 45 Hubble Space Telescope images, or in 50 mock images of lenses with complex distributions of mass. Instead, the best-fit external shear is aligned with the major or minor axis of 88 per cent of lens galaxies; and the amplitude of the external shear increases if that galaxy is discy. We conclude that 'external shear' attached to a power-law model is not physically meaningful, but a fudge to compensate for lack of model complexity. Since it biases other model parameters that are interpreted as physically meaningful in several science analyses (e.g. measuring galaxy evolution, dark matter physics or cosmological parameters), we recommend that future studies of galaxy-scale strong lensing should employ more flexible mass models. [ABSTRACT FROM AUTHOR]

Background Flavorings in cigars increase their appeal, mask the harsh taste of tobacco, and may hinder successful cigar smoking cessation; however, limited evidence has examined whether flavors are associated with short- or long-term cigar smoking cessation. Aims and Methods Using restricted data from the Population Assessment of Tobacco and Health Study Waves 1–5, we examined whether flavored cigar use was associated with 30-day-plus and 1-year-plus cigar smoking cessation among US adults. Multivariable discrete-time survival models were fit to a nationally representative sample of US adult (18+) respondents who had a current, established cigar use, smoked five or more days in the past 30 days, and did not exclusively smoke traditional premium cigars at baseline. Models adjusted for age, sex, race and ethnicity, income, cigar and cigarette smoking intensity, and blunt use. Results At baseline, 44.6% of respondents (n = 674) were 18–34 years old, 75.0% were male, 56.7% were non-Hispanic White, 78.9% had household incomes of <$50,000, and 56.2% smoked flavored cigars. In fully adjusted models, flavored cigar use was associated with a lower risk of 30-day-plus (HR = 0.76, 95% CI = 0.60, 0.97) but not 1-year-plus cigar smoking cessation (HR = 0.81, 95% = 0.62, 1.05). Conclusions We found that flavored cigar use was associated with a lower risk of short-term but not long-term cigar smoking cessation. More work is needed to understand the dynamics of cigar smoking transitions, including initiation, cessation, and relapse, particularly in larger cohorts and among those who exclusively use cigars or dual-use cigars and cigarettes. Implications As local and some state jurisdictions continue to adopt partial or complete bans of flavored cigar products and the United States Food and Drug Administration considers a national ban of all characterizing flavors in cigars, there is a need for more longitudinal work examining the associations between flavorings in cigars and short and long-term cigar-smoking behaviors, including but not limited to initiation, cessation, intensity of use, and relapse, particularly in diverse cohorts. [ABSTRACT FROM AUTHOR]

Sparse and serendipitous asteroid photometry obtained by wide field surveys such as the Asteroid Terrestrial-impact Last Alert System (ATLAS) is a valuable resource for studying the properties of large numbers of small Solar System bodies. We have gathered a large data base of ATLAS photometry in wideband optical cyan and orange filters, consisting of 9.6 × 107 observations of 4.5 × 105 main belt asteroids and Jupiter Trojans. We conduct a phase curve analysis of these asteroids considering each apparition separately, allowing us to accurately reject outlying observations and to remove apparitions and asteroids not suitable for phase curve determination. We obtain a data set of absolute magnitudes and phase parameters for over 100 000 selected asteroids observed by ATLAS, |$\sim 66\, 000$| of which had sufficient measurements to derive colours in the ATLAS filters. To demonstrate the power of our data set we consider the properties of the Nysa–Polana complex, for which the ATLAS colours and phase parameters trace the S-like and C-like compositions amongst family members. We also compare the properties of the leading and trailing groups of Jupiter Trojans, finding no significant differences in their phase parameters or colours as measured by ATLAS, supporting the consensus that these groups were captured from a common source population during planetary migration. Furthermore, we identify ∼9000 asteroids that exhibit large shifts in derived absolute magnitude between apparitions, indicating that these objects have both elongated shapes and spin axes with obliquity ∼90 degrees. [ABSTRACT FROM AUTHOR]

All cometary nuclei that formed in the early Solar System incorporated radionuclides and therefore were subject to internal radiogenic heating. Previous work predicts that if comets have a pebble-pile structure internal temperature build-up is enhanced due to very low thermal conductivity, leading to internal differentiation. An internal thermal gradient causes widespread sublimation and migration of either ice condensates, or gases released from amorphous ice hosts during their crystallization. Overall, the models predict that the degree of differentiation and re-distribution of volatile species to a shallower near-surface layer depends primarily on nucleus size. Hence, we hypothesize that cometary activity should reveal a correlation between the abundance of volatile species and the size of the nucleus. To explore this hypothesis, we have conducted a thorough literature search for measurements of the composition and size of cometary nuclei, compiling these into a unified data base. We report a statistically significant correlation between the measured abundance of CO/H2O and the size of cometary nuclei. We further recover the measured slope of abundance as a function of size, using a theoretical model based on our previous thermophysical models, invoking re-entrapment of outward migrating high volatility gases in the near-surface pristine amorphous ice layers. This model replicates the observed trend and supports the theory of internal differentiation of cometary nuclei by early radiogenic heating. We make our data base available for future studies, and we advocate for collection of more measurements to allow more precise and statistically significant analyses to be conducted in the future. [ABSTRACT FROM AUTHOR]

In recent years, there has been a remarkable development of simulation-based inference (SBI) algorithms, and they have now been applied across a wide range of astrophysical and cosmological analyses. There are a number of key advantages to these methods, centred around the ability to perform scalable statistical inference without an explicit likelihood. In this work, we propose two technical building blocks to a specific sequential SBI algorithm, truncated marginal neural ratio estimation (TMNRE). In particular, first, we develop autoregressive ratio estimation with the aim to robustly estimate correlated high-dimensional posteriors. Secondly, we propose a slice-based nested sampling algorithm to efficiently draw both posterior samples and constrained prior samples from ratio estimators, the latter being instrumental for sequential inference. To validate our implementation, we carry out inference tasks on three concrete examples: a toy model of a multidimensional Gaussian, the analysis of a stellar stream mock observation, and finally, a proof-of-concept application to substructure searches in strong gravitational lensing. In addition, we publicly release the code for both the autoregressive ratio estimator and the slice sampler. [ABSTRACT FROM AUTHOR]

We propose an empirical Bayes formulation of the structure learning problem, where the prior specification assumes that all node variables have the same error variance, an assumption known to ensure the identifiability of the underlying causal directed acyclic graph. To facilitate efficient posterior computation, we approximate the posterior probability of each ordering by that of a best directed acyclic graph model, which naturally leads to an order-based Markov chain Monte Carlo algorithm. Strong selection consistency for our model in high-dimensional settings is proved under a condition that allows heterogeneous error variances, and the mixing behaviour of our sampler is theoretically investigated. Furthermore, we propose a new iterative top-down algorithm, which quickly yields an approximate solution to the structure learning problem and can be used to initialize the Markov chain Monte Carlo sampler. We demonstrate that our method outperforms other state-of-the-art algorithms under various simulation settings, and conclude the paper with a single-cell real-data study illustrating practical advantages of the proposed method. [ABSTRACT FROM AUTHOR]

How does a leader's childhood exposure to war influence their propensity to initiate conflicts? While much research explains leaders' national security policies using their combat and rebel experiences, few scholars have examined the effects of childhood wartime violence. I develop and test two competing arguments about the effects of childhood war trauma on future conflict behavior. One argument expects that leaders exposed to war at a young age will be less likely to initiate conflict because they fear its consequences. An alternative perspective expects that these leaders are more likely to initiate conflict out of anger and a desire for revenge. I test my hypotheses using an original dataset and a research design that reduces inference barriers. Leveraging variations in the level of violence experienced during wartime, I only compare leaders who were exposed to foreign military invasions as children. I find that those who experienced severe war trauma, such as family deaths, injuries, or displacement, are less likely to initiate interstate conflicts than those who did not experience such traumatic events. These effects are substantial, particularly when political constraints are weak. My results suggest that childhood war trauma has a long-term impact on leaders' conservatism about using force. [ABSTRACT FROM AUTHOR]

Why do human rights INGOs choose to work on some issues and not others? This article contends that, since the 1990s, the proliferation of issues within the remit of human rights INGOs has increased the moral opportunity costs of selection decisions. Growth in the number and diversity of issues has led to a "selection dilemma" where decision-makers face onerous ethical choices among a significant menu of options. To explain how decision-makers deal with this dilemma, the article builds on existing theoretical work on INGOs, primarily by constructivists, proposing that heuristic-led judgment on the part of key decision-makers is a central determinant in the (non-)adoption of issues. This explanation is examined empirically using a within-case paired analysis of decision-making in Amnesty International and Human Rights Watch. The article's findings provide preliminary evidence that heuristics shape selection outcomes in INGOs, adding further weight to IR scholarship, which stresses the influence of psychology and leaders in organizational and group decision-making. [ABSTRACT FROM AUTHOR]

Two of the most significant concerns about the contemporary United States are the erosion of democratic institutions and the high rate of depression. We provide evidence connecting these phenomena. We use a survey (N  = 11,517) to show a relationship between misperceptions (about COVID-19 vaccines) and voting, in 2022, for gubernatorial candidates who denied or cast doubt on the legitimacy of the 2020 election results. We further predict and find that the presence of moderately severe-to-severe depressive symptoms exacerbates the relationship between misperceptions and voting for election deniers or doubters. The results offer insight into the links between misperceptions, depression, and democratic backsliding (i.e. supporting candidates who challenge election results). We also contribute to a growing line of research on how mental health affects democratic functioning, potentially worldwide. [ABSTRACT FROM AUTHOR]

The health epidemic of 2020 set off a culture war and, like all national crises, revealed exactly who we Americans are. This essay examines Danielle Allen's Democracy in the Time of Coronavirus , a wise, humane, and indispensable guide for negotiating a health pandemic—if not this one, the inevitable next one. It reflects on her five-point guide to handling pandemics, comparing her ideals to the national experience. This essay places Allen's monograph in the context of the larger literature on the coronavirus in America. The essay traces how and why public health fell into the American culture wars, notes the brief glimmer of a genuine social welfare safety net that briefly emerged during the crisis, and summarizes the epidemic's dismal toll on American lives, suggesting why even much poorer nations did a better job of protecting their citizens. [ABSTRACT FROM AUTHOR]

Objectives In this feasibility study, we explored the combined use of circulating tumor human papillomavirus (HPV) DNA (ctHPVDNA) and HPV serology as diagnostic tests for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Methods Among patients with research-banked serum or plasma at diagnosis, IgG antibodies to oncoproteins from HPV types 16, 18, 31, 33, 35, 45, 52, and 58 were detected with multiplex serology. Positivity for HPV 16 was defined based on detection of combinations of anti-E6, E1, E2, and E7 and for other high-risk types on detection of anti-E6 and anti-E7. Circulating tumor HPV DNA was detected by custom digital droplet polymerase chain reaction (ddPCR) assays for HPV types 16, 18, 33, 35, and 45. p16 immunohistochemistry and high-risk HPV RNA in situ hybridization (ISH) using a cocktail of 18 high-risk HPV types were performed on tissue. Results Of 75 patients, 67 (89.3%) were HPV-associated (p16 and HPV RNA ISH positive) and 8 (10.7%) were HPV-independent. All 8 HPV-independent patients were seronegative and negative for ctHPVDNA (100% specificity). Serology was positive in 53 (79.1%) of 67 HPV-associated patients, while ddPCR was positive for ctHPVDNA in 59 (88.6%) of 67 HPV-associated patients. Requiring both tests to be positive resulted in a sensitivity of 50 (74.6%) of 67 while combining assays (either positive) improved sensitivity to 62 (92.6%) of 67. Conclusions Compared to HPV RNA ISH, HPV serology and ctHPVDNA are sensitive and highly specific biomarkers for HPV-associated OPSCC at the time of presentation. [ABSTRACT FROM AUTHOR]

Background Concerning levels of stress, strain, and poorer mental health are observed in family carers of patients diagnosed with high-grade glioma (HGG). Understanding the reported unmet needs of these carers will enable future interventions to address such needs to improve their preparedness for care and well-being. In this secondary analysis, we aimed to explore: (i) what carers of people with HGG perceive could improve their preparedness to care ; and (ii) what needs carers reported they required additional support with. Methods Responses from 188 carers of patients with HGG participating in a randomized controlled trial of the Care-IS intervention were analyzed to identify reported unmet needs. Of this larger sample, 92 participants answered a qualitative question seeking to identify perceived unmet needs in carer preparedness over 12 months. These responses comprised the data for the current secondary analysis. Content analysis was used to analyze the qualitative data and observe trends across participant responses. Results Five overarching themes were identified: carer needs , providing emotional and practical care , coping with uncertainty , coping with the consequences of illness progression , and processing and supporting end-of-life care. Notably, the content analysis identified differences in response numbers between groups in the Care-IS trial, particularly with the control group having more needs regarding illness progression and end-of-life care. Conclusions Future interventions aimed at improving the well-being and preparedness of carers of people with HGG should consider providing better support centered on carer needs, their changed circumstances, living with uncertainty, and care transition. [ABSTRACT FROM AUTHOR]

This article examines how the Roman Catholic Church in Poland navigated the enormous increase in church buildings at its disposal at the end of the Second World War. This expansion was largely due to the mass acquisition of post-German churches in lands transferred from Germany to Poland. But rapid reconstruction of most of the churches destroyed during the war as well as the resumption of new construction also played a role. Although access to increased worship space might seem to have been a boon for Poland's postwar Catholic Church, the appropriation, reconstruction and completion of thousands of church buildings presented the church with an array of challenges. Refounding local Polish religious life in post-German, and often post-Protestant, houses of worship raised difficult questions about how various constituencies in newly formed communities could be made to feel at home in their new surroundings. Trade-offs between the expectations and customs of divergent groups were exacerbated by the prominence within the postwar church of Catholics who were themselves post-German, having spent the war categorized as German before being recategorized as Polish after 1945. Close attention to how Polish Catholics encountered new sacred spaces and one another reveals the complex negotiations and balancing acts required to form an ostensibly homogeneous religious-national community. [ABSTRACT FROM AUTHOR]

Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6 -associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker. [ABSTRACT FROM AUTHOR]

We use the magnetic field components measured by Zeeman Doppler imaging (ZDI) to calculate the stellar surface force and torque due to magnetic stresses for the fast rotators σ Ori E, 36 Lyn, and CU Vir, and the slow rotator τ Sco. If we assume the stars have spherical photospheres, the estimated torques give spin-down time-scales no larger than 7 × 105 yr. For σ Ori E, the predicted spin-down time-scale, ≃ 6000 yr, is much less than the observationally measured time-scale of ≃ 106 yr. However, for CU Vir, we find that the spin-down time-scale from its ZDI map is 7 × 105 yr in good agreement with its average rate of spin-down from 1960 to 2010. With the exception of τ Sco, the net force due to magnetic stresses at the stellar surface are large compared to the surface-integrated pressure. We discuss possible reasons for the large values of the forces (and torques), and suggest that the likely explanation is that rotation and the magnetic stresses create significant departures from spherical symmetry. [ABSTRACT FROM AUTHOR]

Mass drug administration (MDA) of antifilarial drugs is the main strategy for the elimination of lymphatic filariasis (LF). Recent clinical trials indicated that the triple-drug therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) is much more effective against LF than the widely used two-drug combinations (albendazole plus either ivermectin or diethylcarbamazine). For IDA-based MDA, the stop-MDA decision is made based on microfilariae (mf) prevalence in adults. In this study, we assess how the probability of eventually reaching elimination of transmission depends on the critical threshold used in transmission assessment surveys (TAS-es) to define whether transmission was successfully suppressed and triple-drug MDA can be stopped. This analysis focuses on treatment-naive Indian settings. We do this for a range of epidemiological and programmatic contexts, using the established LYMFASIM model for transmission and control of LF. Based on our simulations, a single TAS, one year after the last MDA round, provides limited predictive value of having achieved suppressed transmission, while a higher MDA coverage increases elimination probability, thus leading to a higher predictive value. Every additional TAS, conditional on previous TAS-es being passed with the same threshold, further improves the predictive value for low values of stop-MDA thresholds. An mf prevalence threshold of 0.5% corresponding to TAS-3 results in ≥95% predictive value even when the MDA coverage is relatively low. [ABSTRACT FROM AUTHOR]

Aims Lethal arrhythmias in hypertrophic cardiomyopathy (HCM) are widely attributed to myocardial ischaemia and fibrosis. How these factors modulate arrhythmic risk remains largely unknown, especially as invasive mapping protocols are not routinely used in these patients. By leveraging multiscale digital twin technologies, we aim to investigate ischaemic mechanisms of increased arrhythmic risk in HCM. Methods and results Computational models of human HCM cardiomyocytes, tissue, and ventricles were used to simulate outcomes of Phase 1A acute myocardial ischaemia. Cellular response predictions were validated with patch-clamp studies of human HCM cardiomyocytes (n = 12 cells, N = 5 patients). Ventricular simulations were informed by typical distributions of subendocardial/transmural ischaemia as analysed in perfusion scans (N = 28 patients). S1-S2 pacing protocols were used to quantify arrhythmic risk for scenarios in which regions of septal obstructive hypertrophy were affected by (i) ischaemia, (ii) ischaemia and impaired repolarization, and (iii) ischaemia, impaired repolarization, and diffuse fibrosis. HCM cardiomyocytes exhibited enhanced action potential and abnormal effective refractory period shortening to ischaemic insults. Analysis of ∼75 000 re-entry induction cases revealed that the abnormal HCM cellular response enabled establishment of arrhythmia at milder ischaemia than otherwise possible in healthy myocardium, due to larger refractoriness gradients that promoted conduction block. Arrhythmias were more easily sustained in transmural than subendocardial ischaemia. Mechanisms of ischaemia–fibrosis interaction were strongly electrophysiology dependent. Fibrosis enabled asymmetric re-entry patterns and break-up into sustained ventricular tachycardia. Conclusion HCM ventricles exhibited an increased risk to non-sustained and sustained re-entry, largely dominated by an impaired cellular response and deleterious interactions with the diffuse fibrotic substrate. [ABSTRACT FROM AUTHOR]

The radial acceleration relation (RAR) connects the total gravitational acceleration of a galaxy at a given radius, a tot(r), with that accounted for by baryons at the same radius, a bar(r). The shape and tightness of the RAR for rotationally-supported galaxies have characteristics in line with MOdified Newtonian Dynamics (MOND) and can also arise within the cosmological constant + cold dark matter (ΛCDM) paradigm. We use zoom simulations of 20 galaxies with stellar masses of M ⋆ ≃ 107–11 M⊙ to study the RAR in the FIRE-2 simulations. We highlight the existence of simulated galaxies with non-monotonic RAR tracks that 'hook' down from the average relation. These hooks are challenging to explain in Modified Inertia theories of MOND, but naturally arise in all of our ΛCDM-simulated galaxies that are dark-matter dominated at small radii and have feedback-induced cores in their dark matter haloes. We show, analytically and numerically, that downward hooks are expected in such cored haloes because they have non-monotonic acceleration profiles. We also extend the relation to accelerations below those traced by disc galaxy rotation curves. In this regime, our simulations exhibit 'bends' off of the MOND-inspired extrapolation of the RAR, which, at large radii, approach a tot ≈ a bar/ f b, where f b is the cosmic baryon fraction. Future efforts to search for these hooks and bends in real galaxies will provide interesting tests for MOND and ΛCDM. [ABSTRACT FROM AUTHOR]

Background A study previously conducted in primary care practices found that implementation of an educational session and peer comparison feedback was associated with reduced antibiotic prescribing for respiratory tract diagnoses (RTDs). Here, we assess the long-term effects of this intervention on antibiotic prescribing following cessation of feedback. Methods RTD encounters were grouped into tiers based on antibiotic prescribing appropriateness: tier 1, almost always indicated; tier 2, possibly indicated; and tier 3, rarely indicated. A χ2 test was used to compare prescribing between 3 time periods: pre-intervention, intervention, and post-intervention (14 months following cessation of feedback). A mixed-effects multivariable logistic regression analysis was performed to assess the association between period and prescribing. Results We analyzed 260 900 RTD encounters from 29 practices. Antibiotic prescribing was more frequent in the post-intervention period than in the intervention period (28.9% vs 23.0%, P <.001) but remained lower than the 35.2% pre-intervention rate (P <.001). In multivariable analysis, the odds of prescribing were higher in the post-intervention period than the intervention period for tier 2 (odds ratio [OR], 1.19; 95% confidence interval [CI]: 1.10–1.30; P <.05) and tier 3 (OR, 1.20; 95% CI: 1.12–1.30) indications but was lower compared to the pre-intervention period for each tier (OR, 0.66; 95% CI: 0.59–0.73 tier 2; OR, 0.68; 95% CI: 0.61–0.75 tier 3). Conclusions The intervention effects appeared to last beyond the intervention period. However, without ongoing provider feedback, there was a trend toward increased prescribing. Future studies are needed to determine optimal strategies to sustain intervention effects. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) and influenza are both typically seasonal diseases, with winter peaks in temperate climates. Coadministration of an RSV vaccine and influenza vaccine could be a benefit, requiring 1 rather than 2 visits to a healthcare provider for individuals receiving both vaccines. Methods The primary immunogenicity objective of this phase 3, 1:1 randomized, double-blind, placebo-controlled study in healthy adults aged ≥65 years in Australia was to demonstrate noninferiority of immune responses with coadministration of the stabilized RSV prefusion F protein–based vaccine (RSVpreF) and seasonal inactivated influenza vaccine (SIIV) versus SIIV or RSVpreF administered alone, using a 1.5-fold noninferiority margin (lower bound 95% confidence interval >.667). Safety and tolerability were evaluated by collecting reactogenicity and adverse event data. Results Of 1403 participants randomized, 1399 received vaccinations (median age, 70; range, 65‒91 years). Local reactions and systemic events were mostly mild or moderate when RSVpreF was coadministered with SIIV or administered alone. No vaccine-related serious adverse events were reported. Geometric mean ratios were 0.86 for RSV-A and 0.85 for RSV-B neutralizing titers at 1 month after RSVpreF administration and 0.77 to 0.90 for strain-specific hemagglutination inhibition assay titers at 1 month after SIIV. All comparisons achieved the prespecified 1.5-fold noninferiority margin. Conclusions The primary study objectives were met, demonstrating noninferiority of RSVpreF and SIIV immune responses when RSVpreF was coadministered with SIIV and that RSVpreF had an acceptable safety and tolerability profile when coadministered with SIIV. The results of this study support coadministration of RSVpreF and SIIV in an older-adult population. Clinical Trials Registration https://clinicaltrials.gov/study/NCT05301322. [ABSTRACT FROM AUTHOR]

M dwarfs are often highly flare productive, and changes in the rate of flaring can potentially affect the radiation and energetic particles an exoplanet is exposed to. Rate variability has been found to be rare on G-type stars, and there has been limited study of the variability of flaring on M dwarfs. Using data from the TESS mission up to Observation Sector 66, we analyse 658 stars ranging from K7 to M5 to test for superflare rate variability by calculating an optimal piecewise constant-rate model for flare occurrence using a Bayesian algorithm and identify 66 stars with rate changes, a larger proportion than our previous study into G-type stars (7 out of 270 stars). We find that rate variability does not depend on the stellar parameters for our sample. We investigate how the flare-frequency distribution for these stars varies and whether this variation affects exoplanet habitability. No stars in our sample provide sufficient UV flux to support prebiotic chemistry. We investigate the phase distributions on the rate variable stars, finding 11 cases of potential phase dependence in flaring across seven stars. We also compare the Bayesian method to another measure of activity, the fraction of flux emitted through flares, and do not observe a consistent relationship between this flaring activity metric and the optimal Bayesian model. We discuss the possible reasons for the discrepancy and identify a problem with the flaring activity metric due to the power-law distribution of the flare events. [ABSTRACT FROM AUTHOR]

Monofluoroacetate is a highly lethal toxin that causes death by inhibiting cellular adenosine triphosphate (ATP) production. The heart and brain are the primary target organs. Acute death is attributed to cardiac fibrillation and/or convulsions. Although it occurs naturally in some plants, a major source of animal intoxication is access to sodium monofluoroacetate (NaMFA) pesticide, which continues to be a concern in the USA and around the world despite restricted use in some countries including the USA. There are also concerns about misuse of this pesticide for malicious poisoning. Currently, a tissue-based diagnostic method for NaMFA intoxication in animals is lacking. There is a critical need by the veterinary diagnostic community for a simple, sensitive and reliable tissue-based diagnostic test to confirm NaMFA poisoning in animals. We have developed and extensively evaluated a sensitive novel liquid chromatography combined with tandem mass spectrometry method suitable for this purpose. The limits of detection and limits of quantitation are 1.7 and 5.0 ng/g, respectively. The accuracy and precision met or exceeded expectations. The method performance was verified using the incurred kidney obtained from animal diagnostic cases. This novel kidney-based method is now available for clinical use and can help with diagnostic purposes, including detecting potential issues related to animal foods. [ABSTRACT FROM AUTHOR]

The UK Biobank study contains several sources of diagnostic data, including hospital inpatient data and data on self-reported conditions for approximately 500,000 participants and primary-care data for approximately 177,000 participants (35%). Epidemiologic investigations require a primary disease definition, but whether to combine data sources to maximize statistical power or focus on only 1 source to ensure a consistent outcome is not clear. The consistency of disease definitions was investigated for venous thromboembolism (VTE) by evaluating overlap when defining cases from 3 sources: hospital inpatient data, primary-care reports, and self-reported questionnaires. VTE cases showed little overlap between data sources, with only 6% of reported events for persons with primary-care data being identified by all 3 sources (hospital, primary-care, and self-reports), while 71% appeared in only 1 source. Deep vein thrombosis–only events represented 68% of self-reported VTE cases and 36% of hospital-reported VTE cases, while pulmonary embolism–only events represented 20% of self-reported VTE cases and 50% of hospital-reported VTE cases. Additionally, different distributions of sociodemographic characteristics were observed; for example, patients in 46% of hospital-reported VTE cases were female, compared with 58% of self-reported VTE cases. These results illustrate how seemingly neutral decisions taken to improve data quality can affect the representativeness of a data set. [ABSTRACT FROM AUTHOR]

TANGO results have established the durable efficacy of dolutegravir/lamivudine in virologically suppressed individuals who switched from 3- or 4-drug tenofovir alafenamide (TAF)–based regimens. In this post hoc subgroup analysis, 144-week efficacy and tolerability of dolutegravir/lamivudine in participants who switched from elvitegravir/cobicistat/emtricitabine/TAF were consistent with the overall switch population. Clinical Trials Registration NCT03446573. [ABSTRACT FROM AUTHOR]

New World mabuyine skinks are a diverse radiation of morphologically cryptic lizards with unique reproductive biologies. Recent studies examining population-level data (morphological, ecological, and genomic) have uncovered novel biodiversity and phenotypes, including the description of dozens of new species and insights into the evolution of their highly complex placental structures. Beyond the potential for this diverse group to serve as a model for the evolution of viviparity in lizards, much of the taxonomic diversity is concentrated in regions experiencing increasing environmental instability from climate and anthropogenic change. Consequently, a better understanding of genome structure and diversity will be an important tool in the adaptive management and conservation of this group. Skinks endemic to Caribbean islands are particularly vulnerable to global change with several species already considered likely extinct and several remaining species either endangered or threatened. Combining PacBio long-read sequencing, Hi-C, and RNAseq data, here we present the first genomic resources for this group by describing new chromosome-level reference genomes for the Puerto Rican Skink Spondylurus nitidus and the Culebra Skink S. culebrae. Results indicate two high quality genomes, both ∼1.4 Gb, assembled nearly telomere to telomere with complete mitochondrion assembly and annotation. [ABSTRACT FROM AUTHOR]

Intrinsic rates of genetic mutation have diverged greatly across taxa and exhibit statistical associations with several other parameters and features. These include effective population size (Ne), genome size, and gametic multicellularity, with the latter being associated with both increased mutation rates and decreased effective population sizes. However, data sufficient to test for possible relationships between microbial multicellularity and mutation rate (µ) are lacking. Here, we report estimates of two key population-genetic parameters, Ne and µ , for Myxococcus xanthus , a bacterial model organism for the study of aggregative multicellular development, predation, and social swarming. To estimate µ , we conducted an ∼400-day mutation accumulation experiment with 46 lineages subjected to regular single colony bottlenecks prior to clonal regrowth. Upon conclusion, we sequenced one clonal-isolate genome per lineage. Given collective evolution for 85,323 generations across all lines, we calculate a per base-pair mutation rate of ∼5.5 × 10−10 per site per generation, one of the highest mutation rates among free-living eubacteria. Given our estimate of µ , we derived Ne at ∼107 from neutral diversity at four-fold degenerate sites across two dozen M. xanthus natural isolates. This estimate is below average for eubacteria and strengthens an already clear negative correlation between µ and Ne in prokaryotes. The higher and lower than average mutation rate and Ne for M. xanthus , respectively, amplify the question of whether any features of its multicellular life cycle—such as group-size reduction during fruiting-body development—or its highly structured spatial distribution have significantly influenced how these parameters have evolved. [ABSTRACT FROM AUTHOR]

As presented in this article, the overall arrest rate for males in the United States no longer peaks during the late teenage years, contrary to the traditional conceptualization of the age-crime curve. Instead of peaking around age 18 and falling throughout adulthood, the overall arrest rate in 2019 did not peak until age 27. Using a dissimilarity index, the results show that the age-crime curve for overall, violent and property offenses during 2019 differs significantly from that of 1985. However, the age-crime curve is still apparent within the data when examined by birth cohort. It appears that a sudden decline in the proportion of offenses committed by 15-to-19-year-old males is responsible for the shift in the aggregate/cross-sectional age-crime curve. [ABSTRACT FROM AUTHOR]

Introduction: Preservation of life, preservation of limb, and preservation of eyesight are the priorities for military medical personnel when attending to casualties. The incidences of eye injuries in modern warfare have increased significantly, despite personal eye equipment for service members. Serious eye injuries are often overlooked or discovered in a delayed fashion because they accompany other life- and limb-threatening injuries, which are assigned a higher priority. Prehospital military ocular trauma care is to shield the eye and evacuate the casualty to definitive ophthalmic care as soon as possible, with exceptions for treatment of ocular chemical injury and orbital compartment syndrome. Retrospective analysis of eye injuries in recent conflicts identified gaps in clinical capabilities with up to 96% of ocular injuries being suboptimally managed. Ocular compartment syndrome (OCS) is a complication associated with orbital hemorrhage, where significant morbidity occurs as a result of increasing intracompartment pressure. The ischemic tolerance of the retina and optic nerve is approximately 90 minutes, so OCS must be rapidly diagnosed and aggressively treated through lateral canthotomy/cantholysis (LC/C) to prevent permanent vision loss. LC/C procedures consist of using hemostats to crush the lateral canthal fold and cutting the lateral canthal tendon from the inferior crus to relieve increasing intracompartment pressure. The purpose of this study was to examine the baseline capabilities of military physicians and surgeons to accurately and independently perform the LC/C procedures and identify performance gaps that could be closed through focused professional development activities.Materials and Methods: This study received institutional review board approval at our institution. A total of 60 subjects voluntarily participated in the study from emergency medicine (15), general surgery (28), and ophthalmology (17). All procedural assessments were performed 1:1 by expert faculty ocular trauma specialists using a high-reliability eye trauma simulator (Sonalysts, Inc.). The competency standard was set at independent and accurate completion of all procedural components and all critical procedural components. Analyses were performed using descriptive statistics and analysis of variance to examine between-group differences (P < 0.05).Results: There was a significant difference between the total score performance and the critical score performance for the three groups (P < 0.001). Outcomes indicate a significant linear relationship between the expertise level of the clinical provider and the procedural performance of LC/C. Outcomes demonstrate the baseline surgical capabilities of the general surgeons transferred to LC/C performance; however, they were unfamiliar with the anatomy and the procedural techniques and requirements. The group of emergency medicine participants demonstrated performance gaps not only in the same areas as the general surgeons but also in their baseline surgical abilities. This suggests that different professional development activities are necessary for surgeons and physicians tasked with performing LC/V procedures.Conclusions: We identified significant performance gaps among emergency medicine physicians, general surgeons, and ophthalmologists in their abilities to recognize and treat OCS through LC/C procedures. These sight-saving procedures are a critical competency for forward-situated clinicians in expeditionary contexts. We identified the need for targeted approaches to professional development for closing the performance gaps for both emergency medicine physicians and general surgeons. [ABSTRACT FROM AUTHOR]

Introduction Reserve and National Guard (RNG) service members face increased risks for psychological and behavioral problems and are unlikely to seek mental health (MH) care after returning from military deployments. This article examines an online intervention (Web-Ed) with regard to participation, screening results, satisfaction, and intent to seek follow-up MH care, with comparisons by gender and post-deployment MH care receipt. Materials and Methods This was a cross-sectional study of 414 RNG service members (214 women and 200 men), who returned from deployments to or in support of the Iraq or Afghanistan wars within the prior 36 months. Participants completed Web-Ed, which includes screening, personalized education, and links to Veterans Health Administration health care. Results Positive post-deployment screening proportions, Web-Ed satisfaction, and intent to seek follow-up care were similar for men and women. Few had received MH care (33% women; 24% men), yet most screened positive on at least one screen (69% women; 72% men). Most indicated that they would recommend Web-Ed to other veterans (71% women; 67% men) and that they received useful information they may not have received otherwise (52% women; 53% men) regardless of gender or prior MH care. Almost half (40% women; 48% men) planned to seek further assessment from a health care provider as a direct result of Web-Ed. Conclusions Efforts to facilitate access to MH care among post-deployed RNG veterans should be ongoing, regardless of the length of time since deployment, Veterans Affairs enrollment status, prior MH care receipt, or gender. Online screening and personalized education engage veterans who have not sought MH care and provide new information to those who have. [ABSTRACT FROM AUTHOR]

Background Everyday discrimination—experiences of being treated unfairly based on background characteristics like race—is linked to poor physical and mental health throughout the lifespan. Whether more experiences of discrimination are associated with higher odds of being hospitalized in older African Americans has not been explored. Methods Community-dwelling participants from 3 longitudinal cohort studies (N  = 446, age 65+ years) with discrimination scores and ≥12 months of linked Medicare claims were included. Hospitalizations were identified using Medicare fee-for-service claims, available for an average of 6.2 (SD : 3.7) years of follow-up after baseline. Results In mixed-effects ordinal logistic regression models (outcomes of 0, 1, or 2+ hospitalizations per year) adjusted for age, sex, education, and income, higher discrimination was associated with higher odds of total annual hospitalizations (odds ratio [OR] per point higher = 1.09, 95% confidence intervals [95% CI]: 1.02–1.17). Results were similar when accounting for depressive symptoms. Conclusions Higher exposure to everyday discrimination is associated with higher odds of hospitalization among older African Americans. Mechanisms underlying associations should be explored further to understand how hospitalizations may be reduced in older African Americans. [ABSTRACT FROM AUTHOR]

Understanding how the early stages of sexual signal diversification proceed is critically important because these microevolutionary dynamics directly shape species trajectories and impact macroevolutionary patterns. Unfortunately, studying this is challenging because signals involve complex interactions between behavior, morphology, and physiology, much of which can only be measured in real-time. In Hawaii, male Pacific field cricket song attracts both females and a deadly parasitoid fly. Over the past two decades, there has been a marked increase in signal variation in Hawaiian populations of these crickets, including novel male morphs with distinct mating songs. We capitalize on this rare opportunity to track changes in morph composition over time in a population with three novel morphs, investigating how mate and parasitoid attraction (components of sexual and natural selection) may shape signal evolution. We find dramatic fluctuation in morph proportions over the three years of the study, including the arrival and rapid increase of one novel morph. Natural and sexual selection pressures act differently among morphs, with some more attractive to mates and others more protected from parasitism. Collectively, our results suggest that differential protection from parasitism among morphs, rather than mate attraction, aligns with recent patterns of phenotypic change in the wild. [ABSTRACT FROM AUTHOR]

Insulin, insulin-like growth factors (IGF) and their receptors are highly expressed in the adult hippocampus. Thus, disturbances in the insulin-IGF signalling pathway may account for the selective vulnerability of the hippocampus to nascent Alzheimer's disease (AD) pathology. In the present study, we examined the predominant IGF-binding protein in the CSF, IGFBP2. CSF was collected from 109 asymptomatic members of the parental history-positive PREVENT-AD cohort. CSF levels of IGFBP2, core AD and synaptic biomarkers were measured using proximity extension assay, ELISA and mass spectrometry. Cortical amyloid-beta (Aβ) and tau deposition were examined using 18F-NAV4694 and flortaucipir. Cognitive assessments were performed during up to 8 years of follow-up, using the Repeatable Battery for the Assessment of Neuropsychological Status. T1-weighted structural MRI scans were acquired, and neuroimaging analyses were performed on pre-specified temporal and parietal brain regions. Next, in an independent cohort, we allocated 241 dementia-free ADNI-1 participants into four stages of AD progression based on the biomarkers CSF Aβ42 and total-tau (t-tau). In this analysis, differences in CSF and plasma IGFBP2 levels were examined across the pathological stages. Finally, IGFBP2 mRNA and protein levels were examined in the frontal cortex of 55 autopsy-confirmed AD and 31 control brains from the Quebec Founder Population (QFP) cohort, a unique population isolated from Eastern Canada. CSF IGFBP2 progressively increased over 5 years in asymptomatic PREVENT-AD participants. Baseline CSF IGFBP2 was positively correlated with CSF AD biomarkers and synaptic biomarkers, and negatively correlated with longitudinal changes in delayed memory (P = 0.024) and visuospatial abilities (P = 0.019). CSF IGFBP2 was negatively correlated at a trend-level with entorhinal cortex volume (P = 0.082) and cortical thickness in the piriform (P = 0.039), inferior temporal (P = 0.008), middle temporal (P = 0.014) and precuneus (P = 0.033) regions. In ADNI-1, CSF (P = 0.009) and plasma (P = 0.001) IGFBP2 were significantly elevated in Stage 2 [CSF Aβ(+)/t-tau(+)]. In survival analyses in ADNI-1, elevated plasma IGFBP2 was associated with a greater rate of AD conversion (hazard ratio = 1.62, P = 0.021). In the QFP cohort, IGFBP2 mRNA was reduced (P = 0.049); however, IGFBP2 protein levels did not differ in the frontal cortex of autopsy-confirmed AD brains (P = 0.462). Nascent AD pathology may induce an upregulation in IGFBP2 in asymptomatic individuals. CSF and plasma IGFBP2 may be valuable markers for identifying CSF Aβ(+)/t-tau(+) individuals and those with a greater risk of AD conversion. [ABSTRACT FROM AUTHOR]

Observations of pulsar scintillation are among the few astrophysical probes of very small-scale (≲ au) phenomena in the interstellar medium (ISM). In particular, characterization of scintillation arcs, including their curvature and intensity distributions, can be related to interstellar turbulence and potentially overpressurized plasma in local ISM inhomogeneities, such as supernova remnants, H  ii regions, and bow shocks. Here we present a survey of eight pulsars conducted at the Five-hundred-metre Aperture Spherical Telescope (FAST), revealing a diverse range of scintillation arc characteristics at high sensitivity. These observations reveal more arcs than measured previously for our sample. At least nine arcs are observed toward B1929+10 at screen distances spanning |$\sim 90~{{\ \rm per\ cent}}$| of the pulsar's 361 pc path length to the observer. Four arcs are observed toward B0355+54, with one arc yielding a screen distance as close as ∼105 au (<1 pc) from either the pulsar or the observer. Several pulsars show highly truncated, low-curvature arcs that may be attributable to scattering near the pulsar. The scattering screen constraints are synthesized with continuum maps of the local ISM and other well-characterized pulsar scintillation arcs, yielding a three-dimensional view of the scattering media in context. [ABSTRACT FROM AUTHOR]

Background Cigarette pack inserts with messages on cessation benefits and advice are a promising labeling policy that may help promote smoking cessation. Purpose To assess insert effects, with and without accompanying pictorial health warning labels(HWLs), on hypothesized psychosocial and behavioral outcomes. Methods We conducted a 2 × 2 between-subject randomized trial (inserts with efficacy messages vs. no inserts; large pictorial HWLs vs. small text HWLs), with 367 adults who smoked at least 10 cigarettes a day. Participants received a 14-day supply of their preferred cigarettes with packs modified to reflect their experimental condition. Over 2 weeks, we surveyed participants approximately 4–5 times a day during their smoking sessions, querying feelings about smoking, level of worry about harms from smoking, self-efficacy to cut down on cigarettes, self-efficacy to quit, hopefulness about quitting, and motivation to quit. Each evening, participants reported their perceived susceptibility to smoking harms and, for the last 24 hr, their frequency of thinking about smoking harms and cessation benefits, conversations about smoking cessation or harms, and foregoing or stubbing out cigarettes before they finished smoking. Mixed-effects ordinal and logistic models were estimated to evaluate differences between groups. Results Participants whose packs included inserts were more likely than those whose packs did not include inserts to report foregoing or stubbing out of cigarettes (OR = 2.39, 95% CI = 1.36, 4.20). Otherwise, no statistically significant associations were found between labeling conditions and outcomes. Conclusions This study provides some evidence, albeit limited, that pack inserts with efficacy messages can promote behaviors that predict smoking cessation attempts. [ABSTRACT FROM AUTHOR]

Severe acute malnutrition (SAM) is the most life-threatening form of undernutrition and underlies at least 10% of all deaths among children younger than 5 years in low-income countries. SAM is a complex, multisystem disease, with physiological perturbations observed in conjunction with the loss of lean mass, including structural and functional changes in many organ systems. Despite the high mortality burden, predominantly due to infections, the underlying pathogenic pathways remain poorly understood. Intestinal and systemic inflammation is heightened in children with SAM. Chronic inflammation and its consequent immunomodulation may explain the increased morbidity and mortality from infections in children with SAM, both during hospitalization and in the longer term after discharge. Recognition of the role of inflammation in SAM is critical in considering new therapeutic targets in this disease, which has not seen a transformational approach to treatment for several decades. This review highlights the central role of inflammation in the wide-ranging pathophysiology of SAM, as well as identifying potential interventions that have biological plausibility based on evidence from other inflammatory syndromes. [ABSTRACT FROM AUTHOR]

Reducing rates of depressive symptoms in older adults is a public health priority. Men's Sheds are a community organisation that may protect against depressive symptoms in older men. It is currently unclear how social anxiety and behavioural activation may relate to depressive symptoms for Men's Shed members. We employed a cross-sectional design to explore whether the relationships between social anxiety, behavioural activation and depressive symptoms were contingent upon Shed social network quality in a sample of 164 Men's Shed members. Conditional effects analysis found social anxiety (B  = -0.08, p < 0.01) and behavioural activation's (B  = 0.02, p < 0.001) relationships with depression to be contingent on Shed social network quality. Additionally, we found evidence for a conditional effect of social anxiety on the relationship between behavioural activation and depression (B  = −0.03, p < 0.01) such that this relationship was stronger for those with higher levels of social anxiety. Our findings suggest that a strong social network within a Men's Shed weakens the association between social anxiety and depression, that the relationship between behavioural activation and depression is stronger in those with poorer Shed social networks, and that the relationship between behavioural activation and depression may be stronger for those with higher levels of social anxiety. We suggest that our findings contribute to increasing quantitative support for the mental health benefits of Men's Shed membership, highlight the potential importance of Shed social network quality and explore how social anxiety may affect the mental health outcomes for members. [ABSTRACT FROM AUTHOR]