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The Korean infrasound catalogue (KIC) covers 1999–2022 and characterizes a rich variety of source types as well as document the effects of the time-varying atmosphere on event detection and location across the Korean Peninsula. The KIC is produced using data from six South Korean infrasound arrays that are cooperatively operated by Southern Methodist University and Korea Institute of Geoscience and Mineral Resources. Signal detection relies on an Adaptive F-Detector that estimates arrival time and backazimuth, which draws a distinction between detection and parameter estimation. Detections and associated parameters are input into a Bayesian Infrasonic Source Location procedure. The resulting KIC contains 38   455 infrasound events and documents repeated events from several locations. The catalogue includes many anthropogenic sources such as an industrial chemical explosion, explosions at limestone open-pit mines and quarries, North Korean underground nuclear explosions and other atmospheric or underwater events of unknown origin. Most events in the KIC occur during working hours and days, suggesting a dominance of human-related signals. The expansion of infrasound arrays over the years in South Korea and the inclusion of data from the International Monitoring System infrasound stations in Russia and Japan increase the number of infrasound events and improve location accuracy because of the increase in azimuthal station coverage. A review of selected events and associated signals at multiple arrays provides a location quality assessment. We quantify infrasound events that have accompanying seismic arrivals (seismoacoustic events) to support the source type assessment. Ray tracing using the Ground-to-Space (G2S) atmospheric model generally predicts observed arrivals when strong stratospheric winds exist, although the predicted arrival times have significant discrepancies. In some cases, local atmospheric data better captures small-scale variations in the wind velocity of the shallow atmosphere and can improve arrival time predictions that are not well matched by the G2S model. The analysis of selected events also illustrates the importance of topographic effects on tropospheric infrasound propagation at local distances. The KIC is the first infrasound catalogue compiled in this region, and it can serve as a valuable data set in developing more robust infrasound source localization and characterization methods. [ABSTRACT FROM AUTHOR]

Background Idiopathic nephrotic syndrome (INS) is a heterogenous disease and current classification is based on observational responses to therapies or kidney histology. The National Unified Renal Translational Research Enterprise (NURTuRE)-INS cohort aims to facilitate novel ways of stratifying INS patients to improve disease understanding, therapeutics and design of clinical trials. Methods NURTuRE-INS is a prospective cohort study of children and adults with INS in a linked biorepository. All recruits had at least one sampling visit collecting serum, plasma, urine and blood for RNA and DNA extraction, frozen within 2 hours of collection. Clinical histology slides and biopsy tissue blocks were also collected. Results A total of 739 participants were recruited from 23 centres to NURTuRE-INS, half of whom were diagnosed in childhood [ n  = 365 (49%)]. The majority were white [ n  = 525 (71%)] and the median age at recruitment was 32 years (interquartile range 12–54). Steroid-sensitive nephrotic syndrome (SSNS) was the most common clinical diagnosis [ n  = 518 (70%)]. Of patients diagnosed in childhood who underwent a kidney biopsy, for SSNS (n  =103), 76 demonstrated minimal change disease (MCD), whereas for steroid-resistant nephrotic syndrome (n  =80), 21 had MCD. Almost all patients diagnosed in adulthood had a kidney biopsy [ n  = 352 (94%)]; 187 had MCD and 162 had focal segmental glomerulosclerosis. Conclusions NURTuRE-INS is a prospective cohort study with high-quality biosamples and longitudinal data that will assist research into the mechanistic stratification of INS. Samples and data will be available through a Strategic Access and Oversight Committee. [ABSTRACT FROM AUTHOR]

In the absence of supplementary heat, the radiative cooling of halo gas around massive galaxies (Milky Way mass and above) leads to an excess of cold gas or stars beyond observed levels. Active galactic nucleus jet-induced heating is likely essential, but the specific properties of the jets remain unclear. Our previous work concludes from simulations of a halo with |$10^{14} \,\mathrm{ M}_\odot$| that a successful jet model should have an energy flux comparable to the free-fall energy flux at the cooling radius and should inflate a sufficiently wide cocoon with a long enough cooling time. In this paper, we investigate three jet modes with constant fluxes satisfying the criteria, including high-temperature thermal jets, cosmic ray (CR)-dominant jets, and widely precessing kinetic jets in |$10^{12}-10^{15}\, {\rm M}_{\odot }$| haloes using high-resolution, non-cosmological magnetohydrodynamic simulations with the FIRE-2 (Feedback In Realistic Environments) stellar feedback model, conduction, and viscosity. We find that scaling the jet energy according to the free-fall energy at the cooling radius can successfully suppress the cooling flows and quench galaxies without violating observational constraints. On the contrary, if we scale the energy flux based on the total cooling rate within the cooling radius, strong interstellar medium cooling dominates this scaling, resulting in a jet flux exceeding what is needed. Among the three jet types, the CR-dominant jet is most effective in suppressing cooling flows across all surveyed halo masses due to enhanced CR pressure support. We confirm that the criteria for a successful jet model work across a wider range, encompassing halo masses of |$10^{12}-10^{15} {\rm M_\odot }$|⁠. [ABSTRACT FROM AUTHOR]

Our ability to trace the star-forming molecular gas is important to our understanding of the Universe. We can trace this gas using CO emission, converting the observed CO intensity into the H |$_2$| gas mass of the region using the CO-to-H |$_2$| conversion factor (⁠|$X_{\rm{{\small CO}}}$|⁠). In this paper, we use simulations to study the conversion factor and the molecular gas within galaxies. We analysed a suite of simulations of isolated disc galaxies, ranging from dwarfs to Milky Way-mass galaxies, that were run using the fire-2 subgrid models coupled to the chimes non-equilibrium chemistry solver. We use the non-equilibrium abundances from the simulations, and we also compare to results using abundances assuming equilibrium, which we calculate from the simulation in post-processing. Our non-equilibrium simulations are able to reproduce the relation between CO and H |$_2$| column densities, and the relation between |$X_{\rm{{\small CO}}}$| and metallicity, seen within observations of the Milky Way. We also compare to the xCOLD GASS survey, and find agreement with their data to our predicted CO luminosities at fixed star formation rate. We also find the multivariate function used by xCOLD GASS overpredicts the H |$_2$| mass for our simulations, motivating us to suggest an alternative multivariate function of our fitting, though we caution that this fitting is uncertain due to the limited range of galaxy conditions covered by our simulations. We also find that the non-equilibrium chemistry has little effect on the conversion factor (<5 per cent) for our high-mass galaxies, though still affects the H |$_2$| mass and |$L_{\rm{{\small CO}}}$| by |$\approx$| 25  per cent. [ABSTRACT FROM AUTHOR]

We investigate the formation of dense stellar clumps in a suite of high-resolution cosmological zoom-in simulations of a massive, star-forming galaxy at z ∼ 2 under the presence of strong quasar winds. Our simulations include multiphase ISM physics from the Feedback In Realistic Environments (FIRE) project and a novel implementation of hyper-refined accretion disc winds. We show that powerful quasar winds can have a global negative impact on galaxy growth while in the strongest cases triggering the formation of an off-centre clump with stellar mass |${\rm M}_{\star }\sim 10^{7}\, {\rm M}_{\odot }$|⁠ , effective radius |${\rm R}_{\rm 1/2\, \rm Clump}\sim 20\, {\rm pc}$|⁠ , and surface density |$\Sigma _{\star } \sim 10^{4}\, {\rm M}_{\odot }\, {\rm pc}^{-2}$|⁠. The clump progenitor gas cloud is originally not star-forming, but strong ram pressure gradients driven by the quasar winds (orders of magnitude stronger than experienced in the absence of winds) lead to rapid compression and subsequent conversion of gas into stars at densities much higher than the average density of star-forming gas. The AGN-triggered star-forming clump reaches |${\rm SFR} \sim 50\, {\rm M}_{\odot }\, {\rm yr}^{-1}$| and |$\Sigma _{\rm SFR} \sim 10^{4}\, {\rm M}_{\odot }\, {\rm yr}^{-1}\, {\rm kpc}^{-2}$|⁠ , converting most of the progenitor gas cloud into stars in ∼2 Myr, significantly faster than its initial free-fall time and with stellar feedback unable to stop star formation. In contrast, the same gas cloud in the absence of quasar winds forms stars over a much longer period of time (∼35 Myr), at lower densities, and losing spatial coherency. The presence of young, ultra-dense, gravitationally bound stellar clumps in recently quenched galaxies could thus indicate local positive feedback acting alongside the strong negative impact of powerful quasar winds, providing a plausible formation scenario for globular clusters. [ABSTRACT FROM AUTHOR]

Background and Aims This post hoc analysis assessed the efficacy and safety of upadacitinib in patients with moderately to severely active ulcerative colitis stratified by corticosteroid use from the ulcerative colitis Phase 3 clinical trial programme. Methods Patients were randomised [1:2] to 8 weeks' placebo or upadacitinib 45 mg once daily; Week 8 responders were re-randomised [1:1:1] to 52 weeks' placebo or upadacitinib 15 or 30 mg daily. Corticosteroid dose was kept stable during induction but tapered according to a protocol-defined schedule [or investigator discretion] during maintenance Weeks 0–8. Efficacy outcomes and exposure-adjusted, treatment-emergent adverse event [TEAE] rates were assessed for induction and maintenance stratified by corticosteroid use at induction baseline. Results Overall, 377/988 [38%] patients were receiving corticosteroids at induction baseline [placebo, n  = 133; upadacitinib 45 mg, n  = 244] and 252 [37%] of the 681 clinical responders who entered maintenance were on corticosteroids at induction baseline [ n  = 84 for each treatment]. Similar proportions of patients receiving upadacitinib achieved clinical remission per Adapted Mayo Score with and without baseline corticosteroids at Weeks 8 and 52. The total proportion of patients re-initiating corticosteroids was higher with placebo [24/84;29%] vs upadacitinib 15 mg [16/81; 20%)] and 30 mg [11/81; 14%]. During induction, patients receiving corticosteroids at baseline had higher rates of TEAEs, serious TEAEs, and serious infections vs those not receiving corticosteroids; however, TEAE rates were similar during maintenance after corticosteroid withdrawal. Conclusions Upadacitinib is an effective steroid-sparing treatment in patients with moderately to severely active ulcerative colitis. Clinicaltrials.gov identifiers: NCT02819635 ; NCT03653026 [ABSTRACT FROM AUTHOR]

There are important differences in the performance and outcomes of breast cancer screening in the prevalent compared to the incident screening rounds. The prevalent screen is the first screening examination using a particular imaging technique and identifies pre-existing, undiagnosed cancers in the population. The incident screen is any subsequent screening examination using that technique. It is expected to identify fewer cancers than the prevalent screen because it captures only those cancers that have become detectable since the prior screening examination. The higher cancer detection rate at prevalent relative to incident screening should be taken into account when analyzing the medical audit and effectiveness of new screening technologies. [ABSTRACT FROM AUTHOR]

Background Around 15% of adults aged over 65 live with moderate or severe frailty. Contractual requirements for management of frailty are minimal and neither incentivised nor reinforced. Previous research has shown frailty identification in primary care is ad hoc and opportunistic, but there has been little focus on the challenges of frailty management, particularly within the context of recent introduction of primary care networks and an expanding allied health professional workforce. Aim Explore the views of primary care clinicians in England on the management of frailty. Design and setting Semi-structured interviews were conducted with clinicians across England, including general practitioners (GPs), physician associates, nurse practitioners, paramedics and clinical pharmacists. Thematic analysis was facilitated through NVivo (Version 12). Results A total of 31 clinicians participated. Frailty management was viewed as complex and outside of clinical guidelines with medication optimisation highlighted as a key example. Senior clinicians, particularly experienced GPs, were more comfortable with managing risk. Relational care was important in prioritising patient wishes and autonomy, for instance to remain at home despite deteriorations in health. In settings where more formalised multidisciplinary frailty services had been established this was viewed as successful by clinicians involved. Conclusion Primary care clinicians perceive frailty as best managed through trusted relationships with patients, and with support from experienced clinicians. New multidisciplinary working in primary care could enhance frailty services, but must keep continuity in mind. There is a lack of evidence or guidance for specific interventions or management approaches. [ABSTRACT FROM AUTHOR]

We investigate how the recovery of galaxy star formation rates (SFRs) using energy-balance spectral energy distribution (SED) fitting codes depends on their recent star formation histories (SFHs). We use the magphys and prospector codes to fit 6706 synthetic SEDs of simulated massive galaxies at 1 < z < 8 from the Feedback in Realistic Environments project. We identify a previously unknown systematic error in the magphys results due to bursty star formation: the derived SFRs can differ from the truth by as much as 1 dex, at large statistical significance (>5σ), depending on the details of their recent SFH. SFRs inferred using prospector with non-parametric SFHs do not exhibit this trend. We show that using parametric SFHs (pSFHs) causes SFR uncertainties to be underestimated by a factor of up to 5×. Although this undoubtedly contributes to the significance of the systematic, it cannot explain the largest biases in the SFRs of the starbursting galaxies, which could be caused by details of the stochastic prior sampling or the burst implementation in the magphys libraries. We advise against using pSFHs and urge careful consideration of starbursts when SED modelling galaxies where the SFR may have changed significantly over the last ∼100 Myr, such as recently quenched galaxies, or those experiencing a burst. This concern is especially relevant, e.g. when fitting JWST observations of very high redshift galaxies. [ABSTRACT FROM AUTHOR]

Utilitarians think that what matters in ethics is making the world a better place. In that case, it might seem that we each rationally ought to do our best —perform the actions, out of those open to each of us, with the best expected outcomes. In other words, we should follow act-utilitarian reasons. But often the result of many altruistic agents following such individualistic reasons is worse than the result of them following collectivist 'team-reasons'. So utilitarians should reject act utilitarianism, and accept a dualist view according to which both individualistic and team reasons are fundamental. In order to align these distinct kinds of reason, utilitarians must focus centrally on questions of political and social reform—as did their historical forebears. [ABSTRACT FROM AUTHOR]

Comprehensive characterization of structural variation in natural populations has only become feasible in the last decade. To investigate the population genomic nature of structural variation, reproducible and high-confidence structural variation callsets are first required. We created a population-scale reference of the genome-wide landscape of structural variation across 33 Nordic house sparrows (Passer domesticus). To produce a consensus callset across all samples using short-read data, we compare heuristic-based quality filtering and visual curation (Samplot/PlotCritic and Samplot-ML) approaches. We demonstrate that curation of structural variants is important for reducing putative false positives and that the time invested in this step outweighs the potential costs of analyzing short-read–discovered structural variation data sets that include many potential false positives. We find that even a lenient manual curation strategy (e.g. applied by a single curator) can reduce the proportion of putative false positives by up to 80%, thus enriching the proportion of high-confidence variants. Crucially, in applying a lenient manual curation strategy with a single curator, nearly all (>99%) variants rejected as putative false positives were also classified as such by a more stringent curation strategy using three additional curators. Furthermore, variants rejected by manual curation failed to reflect the expected population structure from SNPs, whereas variants passing curation did. Combining heuristic-based quality filtering with rapid manual curation of structural variants in short-read data can therefore become a time- and cost-effective first step for functional and population genomic studies requiring high-confidence structural variation callsets. [ABSTRACT FROM AUTHOR]

Transposable elements (TEs) are major components of eukaryotic genomes and are implicated in a range of evolutionary processes. Yet, TE annotation and characterization remain challenging, particularly for nonspecialists, since existing pipelines are typically complicated to install, run, and extract data from. Current methods of automated TE annotation are also subject to issues that reduce overall quality, particularly (i) fragmented and overlapping TE annotations, leading to erroneous estimates of TE count and coverage, and (ii) repeat models represented by short sections of total TE length, with poor capture of 5′ and 3′ ends. To address these issues, we present Earl Grey, a fully automated TE annotation pipeline designed for user-friendly curation and annotation of TEs in eukaryotic genome assemblies. Using nine simulated genomes and an annotation of Drosophila melanogaster , we show that Earl Grey outperforms current widely used TE annotation methodologies in ameliorating the issues mentioned above while scoring highly in benchmarking for TE annotation and classification and being robust across genomic contexts. Earl Grey provides a comprehensive and fully automated TE annotation toolkit that provides researchers with paper-ready summary figures and outputs in standard formats compatible with other bioinformatics tools. Earl Grey has a modular format, with great scope for the inclusion of additional modules focused on further quality control and tailored analyses in future releases. [ABSTRACT FROM AUTHOR]

Religion and family remain tightly linked institutions, but the increasingly varied period of emerging adulthood, which includes delays in marriage transition and reduced religiosity overall, calls for additional research into this relationship. Religious involvement continues to be associated with earlier age at first marriage, for example, but the specific mechanisms responsible for this connection are often only implied or untested. Accordingly, we build on prior literature and hypothesize about three mechanisms that could explain the link between adolescent religiosity and marriage transition in young adulthood: the importance of completing milestone goals prior to marriage, such as completing one's education and establishing a career, the importance of cohabitation before marriage, and the ideal age of marriage. We use longitudinal data from the National Study of Youth and Religion to investigate each of these mechanisms for a recent cohort of young adults. Using structural equation modeling and measures for adolescent religious attendance, importance, and affiliation, we find that adolescent religiosity is related to the marriage transition primarily through the mechanism of cohabitation. Specifically, religious attendance and importance in adolescence are associated with less support for cohabitation, which in turn is associated with a higher likelihood of marriage transition during young adulthood. Findings for religious affiliation were not as consistent. In the context of demographic shifts in marriage patterns and religious involvement, these analyses provide an important illustration of how these social institutions are still connected. [ABSTRACT FROM AUTHOR]

Observations of local star-forming galaxies (SFGs) show a tight correlation between their singly ionized carbon line luminosity (⁠|$L_{\rm [C\, {\small II}]}$|⁠) and star formation rate (SFR), suggesting that |$L_{\rm [C\, {\small II}]}$| may be a useful SFR tracer for galaxies. Some other galaxy populations, however, are found to have lower |$L_{\rm [C\, {\small II}]}{}/{}\rm SFR$| than local SFGs, including the infrared (IR)-luminous, starburst galaxies at low and high redshifts as well as some moderately SFGs at the epoch of re-ionization (EoR). The origins of this ' |$\rm [C\, {\small II}]$| deficit' is unclear. In this work, we study the |$L_{\rm [C\, {\small II}]}$| –SFR relation of galaxies using a sample of z  = 0–8 galaxies with |$M_*\approx 10^7-5\times 10^{11}\, \mathrm{M}_\odot$| extracted from cosmological volume and zoom-in simulations from the Feedback in Realistic Environments (fire) project. We find a simple analytic expression for |$L_{\rm [C\, {\small II}]}$| /SFR of galaxies in terms of the following parameters: mass fraction of |$\rm [C\, {\small II}]$| -emitting gas (⁠|$f_{\rm [C\, {\small II}]}$|⁠), gas metallicity (Z gas), gas density (n gas), and gas depletion time (⁠|$t_{\rm dep}{}={}M_{\rm gas}{}/{}\rm SFR$|⁠). We find two distinct physical regimes: |$\rm H_2$| -rich galaxies, where t dep is the main driver of the |$\rm [C\, {\small II}]$| deficit and |$\rm H_2$| -poor galaxies where Z gas is the main driver. The observed |$\rm [C\, {\small II}]$| deficit of IR-luminous galaxies and early EoR galaxies, corresponding to the two different regimes, is due to short gas depletion time and low gas metallicity, respectively. Our result indicates that the |$\rm [C\, {\small II}]$| deficit is a common phenomenon of galaxies, and caution needs to be taken when applying a constant |$L_{\rm [C\, {\small II}]}$| -to-SFR conversion factor derived from local SFGs to estimate cosmic SFR density at high redshifts and interpret data from upcoming |$\rm [C\, {\small II}]$| line intensity mapping experiments. [ABSTRACT FROM AUTHOR]

Objectives The objective of this scoping review is to map methods used to study medication safety following electronic health record (EHR) implementation. Patterns and methodological gaps can provide insight for future research design. Materials and methods We used the Joanna Briggs Institute scoping review methodology and a custom data extraction table to summarize the following data: (1) study demographics (year, country, setting); (2) study design, study period, data sources, and measures; (3) analysis strategy; (4) identified limitations or recommendations; (5) quality appraisal; and (6) if a Safety-I or Safety-II perspective was employed. Results We screened 5879 articles. One hundred and fifteen articles met our inclusion criteria and were assessed for eligibility by full-text review. Twenty-seven articles were eligible for extraction. Discussion and conclusion We found little consistency in how medication safety following EHR implementation was studied. Three study designs, 7 study settings, and 10 data sources were used across 27 articles. None of the articles shared the same combination of design, data sources, study periods, and research settings. Outcome measures were neither defined nor measured consistently. It may be difficult for researchers to aggregate and synthesize medication safety findings following EHR implementation research. All studies but one used a Safety-I perspective to study medication safety. We offer a conceptual model to support a more consistent approach to studying medication safety following EHR implementation. [ABSTRACT FROM AUTHOR]

Objectives To investigate the risk of adverse outcomes following discordant antibiotic treatment (urinary organism resistant) for culture-confirmed community-onset lower urinary tract infection (UTI). Methods Cohort study using routinely collected linked primary care, secondary care and microbiology data from patients with culture-confirmed community-onset lower UTI (COLUTI). Antibiotic treatment within ±3 days was considered concordant if the urinary organism was sensitive and discordant if resistant. The primary outcome was the proportion of patients experiencing urinary infection-related hospital admission (UHA) within 30 days. Secondary outcomes were the proportion of patients experiencing reconsultation within 30 days, and the odds of UHA and reconsultation following discordant treatment, adjusting for sex, age, risk factors for complicated UTI, previous antibiotic treatment, recurrent UTI and comorbidities. Results A total of 11 963 UTI episodes in 8324 patients were included, and 1686 episodes (14.1%, 95% CI 13.5%–14.7%) were discordant. UHA occurred in 212/10 277 concordant episodes (2.1%, 95% CI 1.8%–2.4%) and 88/1686 discordant episodes (5.2%, 95% CI 4.2%–6.4%). Reconsultation occurred in 3961 concordant (38.5%, 95% CI 37.6%–39.5%) and 1472 discordant episodes (87.3%, 95% CI 85.6%–88.8%). Discordant treatment compared with concordant was associated with increased odds of UHA (adjusted OR 2.31, 95% CI 1.77–3.0, P < 0.001) and reconsultation (adjusted OR 11.25, 95% CI 9.66–13.11, P < 0.001) on multivariable analysis. Chronic kidney disease and diabetes mellitus were also independently associated with increased odds of UHA. Conclusions One in seven COLUTI episodes in primary care were treated with discordant antibiotics. In higher risk patients requiring urine culture, empirical antibiotic choice optimization could meaningfully reduce adverse outcomes. [ABSTRACT FROM AUTHOR]

Forward-modeling observables from galaxy simulations enables direct comparisons between theory and observations. To generate synthetic spectral energy distributions (SEDs) that include dust absorption, re-emission, and scattering, Monte Carlo radiative transfer is often used in post-processing on a galaxy-by-galaxy basis. However, this is computationally expensive, especially if one wants to make predictions for suites of many cosmological simulations. To alleviate this computational burden, we have developed a radiative transfer emulator using an artificial neural network (ANN), ANNgelina , that can reliably predict SEDs of simulated galaxies using a small number of integrated properties of the simulated galaxies: star formation rate, stellar and dust masses, and mass-weighted metallicities of all star particles and of only star particles with age <10 Myr. Here, we present the methodology and quantify the accuracy of the predictions. We train the ANN on SEDs computed for galaxies from the IllustrisTNG project's TNG50 cosmological magnetohydrodynamical simulation. ANNgelina is able to predict the SEDs of TNG50 galaxies in the ultraviolet (UV) to millimetre regime with a typical median absolute error of ∼7 per cent. The prediction error is the greatest in the UV, possibly due to the viewing-angle dependence being greatest in this wavelength regime. Our results demonstrate that our ANN-based emulator is a promising computationally inexpensive alternative for forward-modeling galaxy SEDs from cosmological simulations. [ABSTRACT FROM AUTHOR]

The Coyote (Canis latrans) is one of the most studied species in North America with at least 445 papers on its diet alone. While this research has yielded excellent reviews of what coyotes eat, it has been inadequate to draw deeper conclusions because no synthesis to date has considered prey availability. We accounted for prey availability by investigating the prey selection of coyotes across its distribution using the traditional Jacobs' index method, as well as the new iterative preference averaging (IPA) method on scats and biomass. We found that coyotes selected for Dall's Sheep (Ovis dalli), White-tailed Deer (Odocoileus virginianus), Eastern Cottontail Rabbit (Sylvilagus floridanus), and California Vole (Microtus californicus), which yielded a predator-to-preferred prey mass ratio of 1:2. We also found that coyotes avoided preying on other small mammals, including carnivorans and arboreal species. There was strong concordance between the traditional and IPA method on scats, but this pattern was weakened when biomass was considered. General linear models revealed that coyotes preferred to prey upon larger species that were riskier to hunt, reflecting their ability to hunt in groups, and were least likely to hunt solitary species. Coyotes increasingly selected Mule Deer (O. hemionus) and Snowshoe Hare (Lepus americanus) at higher latitudes, whereas Black-tailed Jackrabbit (L. californicus) were increasingly selected toward the tropics. Mule Deer were increasingly selected at higher coyote densities, while Black-tailed Jackrabbit were increasingly avoided at higher coyote densities. Coyote predation could constrain the realized niche of prey species at the distributional limits of the predator through their increased efficiency of predation reflected in increased prey selection values. These results are integral to improved understandings of Coyote ecology and can inform predictive analyses allowing for spatial variation, which ultimately will lead to better understandings about the ecological role of the coyote across different ecosystems. [ABSTRACT FROM AUTHOR]

Both observations and simulations have shown strong evidence for highly time-variable star formation in low-mass and/or high-redshift galaxies, which has important observational implications because high-redshift galaxy samples are rest-ultraviolet (rest-UV) selected and therefore particularly sensitive to the recent star formation. Using a suite of cosmological 'zoom-in' simulations at z > 5 from the Feedback in Realistic Environments project, we examine the implications of bursty star formation histories for observations of high-redshift galaxies with JWST. We characterize how the galaxy observability depends on the star formation history. We also investigate selection effects due to bursty star formation on the physical properties measured, such as the gas fraction, specific star formation rate, and metallicity. We find the observability to be highly time-dependent for galaxies near the survey's limiting flux due to the star formation rate variability: as the star formation rate fluctuates, the same galaxy oscillates in and out of the observable sample. The observable fraction |$f_\mathrm{obs} = 50~{{\ \rm per\ cent}}$| at z ∼ 7 and M ⋆ ∼ 108.5– |$10^{9}\, {\rm M}_{\odot }$| for a JWST /NIRCam survey reaching a limiting magnitude of |$m^\mathrm{lim}_\mathrm{AB} \sim 29{\!-\!}30$|⁠ , representative of surveys such as JADES and CEERS. JWST -detectable galaxies near the survey limit tend to have properties characteristic of galaxies in the bursty phase: on average, they show approximately 2.5 times higher cold, dense gas fractions and 20 times higher specific star formation rates at a given stellar mass than galaxies below the rest-UV detection threshold. Our study represents a first step in quantifying selection effects and the associated biases due to bursty star formation in studying high-redshift galaxy properties. [ABSTRACT FROM AUTHOR]

The size of the home range of a mammal is affected by numerous factors. However, in the normally solitary, but polygynous, Leopard (Panthera pardus), home range size and maintenance is complicated by their transitory social grouping behavior, which is dependent on life history stage and/or reproductive status. In addition, the necessity to avoid competition with conspecifics and other large predators (including humans) also impacts upon home range size. We used movement data from 31 sites across Africa, comprising 147 individuals (67 males and 80 females) to estimate the home range sizes of leopards. We found that leopards with larger home ranges, and in areas with more vegetation, spent longer being active and generally traveled faster, and in straighter lines, than leopards with smaller home ranges. We suggest that a combination of bottom-up (i.e. preferred prey availability), top-down (i.e. competition with conspecifics), and reproductive (i.e. access to mates) factors likely drive the variability in Leopard home range sizes across Africa. However, the maintenance of a large home range is energetically expensive for leopards, likely resulting in a complex evolutionary trade-off between the satisfaction of basic requirements and preventing potentially dangerous encounters with conspecifics, other predators, and people. [ABSTRACT FROM AUTHOR]

Background and Objectives Pain treatments and their efficacy have been studied extensively. Yet surprisingly little is known about the types of treatments, and combinations of treatments, that community-dwelling adults use to manage pain, as well as how treatment types are associated with individual characteristics and national-level context. To fill this gap, we evaluated self-reported pain treatment types among community-dwelling adults in the United States and Canada. We also assessed how treatment types correlate with individuals' pain levels, sociodemographic characteristics, and country of residence, and identified unique clusters of adults in terms of treatment combinations. Research Design and Methods We used the 2020 "Recovery and Resilience" United States–Canada general online survey with 2 041 U.S. and 2 072 Canadian community-dwelling adults. Respondents selected up to 10 pain treatment options including medication, physical therapy, exercise, etc. and an open-ended item was available for self-report of any additional treatments. Data were analyzed using descriptive, regression-based, and latent class analyses. Results Over-the-counter (OTC) medication was reported most frequently (by 55% of respondents, 95% CI 53%–56%), followed by "just living with pain" (41%, 95% CI 40%–43%) and exercise (40%, 95% CI 38%–41%). The modal response (29%) to the open-ended item was cannabis use. Pain was the most salient correlate, predicting a greater frequency of all pain treatments. Country differences were generally small; a notable exception was alcohol use, which was reported twice as often among U.S. versus Canadian adults. Individuals were grouped into 5 distinct clusters: 2 groups relied predominantly on medication (prescription or OTC), another favored exercise and other self-care approaches, one included adults "just living with" pain, and the cluster with the highest pain levels employed all modalities heavily. Discussion and Implications Our findings provide new insights into recent pain treatment strategies among North American adults and identify population subgroups with potentially unmet need for more adaptive and effective pain management. [ABSTRACT FROM AUTHOR]

'Runaway stars' might play a role in driving galactic outflows and enriching the circumgalactic medium with metals. To study this effect, we carry out high-resolution dwarf galaxy simulations that include velocity 'kicks' to massive stars above eigth solar masses. We consider two scenarios, one that adopts a power law velocity distribution for kick velocities, resulting in more stars with high-velocity kicks, and a more moderate scenario with a Maxwellian velocity distribution. We explicitly resolve the multiphase interstellar medium (ISM) and include non-equilibrium cooling and chemistry. We sample individual massive stars from an IMF and follow their radiation input and SN feedback (core-collapse) channel at the end of their lifetime. In the simulations with runaway stars, we add additional (natal) velocity kicks that mimic two- and three-body interactions that cannot be fully resolved in our simulations. We find that including runaway or 'walkaway' star scenarios impacts mass, metal, momentum, and energy outflows as well as the corresponding loading factors. The effect on the mass loading factor is small, but we find an increase in the metal loading by a factor of 1.5 to 2. The momentum loading increases by a factor of 1.5–2. The energy loading increases by roughly a factor of 5 when runaway stars are included. Additionally, we find that the overall level of star formation is increased in the models that include runaway stars. We conclude that the inclusion of runaway stars could have an impact on the global star formation and subsequent outflow properties of dwarf galaxies. [ABSTRACT FROM AUTHOR]

Recent observations indicate that galactic outflows are ubiquitous in high-redshift (high- z) galaxies, including normal star-forming galaxies, quasar hosts, and dusty star-forming galaxies (DSFGs). However, the impact of outflows on the evolution of their hosts is still an open question. Here, we analyse the star-formation histories and galactic outflow properties of galaxies in massive haloes (⁠|$10^{12}\, {\rm M}_{\odot }\ \lt\ M_{\rm vir}\ \lt\ 5\times 10^{12}\, {\rm M}_{\odot }$|⁠) at z ≳ 5.5 in three zoom-in cosmological simulations from the MassiveFIRE suite, as part of the Feedback In Realistic Environments (FIRE) project. The simulations were run with the FIRE-2 model, which does not include feedback from active galactic nuclei. The simulated galaxies resemble z > 4 DSFGs, with star-formation rates of |$\sim\!{1000}\ {\rm M}_{\odot }\, \rm yr^{-1}$| and molecular gas masses of M mol ∼ 1010 M⊙. However, the simulated galaxies are characterized by higher circular velocities than those observed in high- z DSFGs. The mass loading factors from stellar feedback are of the order of ∼0.1, implying that stellar feedback is inefficient in driving galactic outflows and gas is consumed by star formation on much shorter time-scales than it is expelled from the interstellar medium. We also find that stellar feedback is highly inefficient in self-regulating star formation in this regime, with an average integrated star formation efficiency (SFE) per dynamical time of 30 per cent. Finally, compared with FIRE-2 galaxies hosted in similarly massive haloes at lower redshift, we find lower mass loading factors and higher SFEs in the high- z sample. We argue that both effects originate from the higher total and gas surface densities that characterize high- z massive systems. [ABSTRACT FROM AUTHOR]

Background and Aims To inform their future use in regulated clinical trials to evaluate treatment efficacy hypotheses, the measurement properties of three histological indices, Geboes Score [GS], Robarts Histopathology Index [RHI] and Nancy Index [NI], were evaluated among patients with ulcerative colitis. Methods Analyses were conducted on data from a Phase 3 clinical trial of adalimumab [M14-033, n  = 491] and focused on evaluating the measurement properties of the GS, RHI and NI. Specifically, internal consistency and inter-rater reliability, convergent, discriminant and known-group validity, and sensitivity to change were assessed at Baseline, and at Weeks 8 and 52. Results Internal consistency for the RHI showed lower alpha [α] values at Baseline [α = 0.62] relative to Weeks 8 [α = 0.82] and 52 [α = 0.81]. The inter-rater reliability values of RHI [0.91], NI [0.64] and GS [0.53] were excellent, good and fair, respectively. Regarding validity, Week 52 correlations were moderate to strong between full and partial Mayo scores and Mayo subscale scores and the RHI and GS, and were weak to moderate for the NI. Significant differences between mean scores of all three histological indices were observed across known-groups based on Mayo endoscopy subscores and full Mayo scores at Weeks 8 and 52 [ p  < 0.001]. Conclusions The GS, RHI and NI are each capable of producing reliable and valid scores that are sensitive to changes in disease activity over time, in patients with moderately to severely active ulcerative colitis. While all three indices demonstrated relatively acceptable measurement properties, the GS and RHI performed better than the NI. [ABSTRACT FROM AUTHOR]

As they grow, galaxies can transition from irregular/spheroidal with 'bursty' star formation histories (SFHs), to discy with smooth SFHs. But even in simulations, the direct physical cause of such transitions remains unclear. We therefore explore this in a large suite of numerical experiments re-running portions of cosmological simulations with widely varied physics, further validated with existing FIRE simulations. We show that gas supply, cooling/thermodynamics, star formation model, Toomre scale, galaxy dynamical times, and feedback properties do not have a direct causal effect on these transitions. Rather, both the formation of discs and cessation of bursty star formation are driven by the gravitational potential, but in different ways. Disc formation is promoted when the mass profile becomes sufficiently centrally concentrated in shape (relative to circularization radii): we show that this provides a well-defined dynamical centre, ceases to support the global 'breathing modes' that can persist indefinitely in less-concentrated profiles and efficiently destroy discs, promotes orbit mixing to form a coherent angular momentum, and stabilizes the disc. Smooth SF is promoted by the potential or escape velocity V esc (not circular velocity V c) becoming sufficiently large at the radii of star formation that cool, mass-loaded (momentum-conserving) outflows are trapped/confined near the galaxy, as opposed to escaping after bursts. We discuss the detailed physics, how these conditions arise in cosmological contexts, their relation to other correlated phenomena (e.g. inner halo virialization, vertical disc 'settling'), and observations. [ABSTRACT FROM AUTHOR]

Recent works have suggested that energy balance spectral energy distribution (SED) fitting codes may be of limited use for studying high-redshift galaxies for which the observed ultraviolet and far-infrared emission are offset (spatially 'decoupled'). It has been proposed that such offsets could lead energy balance codes to miscalculate the overall energetics, preventing them from recovering such galaxies' true properties. In this work, we test how well the SED fitting code magphys can recover the stellar mass, star formation rate (SFR), specific SFR, dust mass, and luminosity by fitting 6706 synthetic SEDs generated from four zoom-in simulations of dusty, high-redshift galaxies from the FIRE project via dust continuum radiative transfer. Comparing our panchromatic results (using wavelengths 0.4–500 μm, and spanning 1 < z < 8) with fits based on either the starlight (⁠|$\lambda _\mathrm{eff} \le 2.2\, \mu$| m) or dust (⁠|$\ge 100\, \mu$| m) alone, we highlight the power of considering the full range of multiwavelength data alongside an energy balance criterion. Overall, we obtain acceptable fits for 83 per cent of the synthetic SEDs, though the success rate falls rapidly beyond z ≈ 4, in part due to the sparser sampling of the priors at earlier times since SFHs must be physically plausible (i.e. shorter than the age of the universe). We use the ground truth from the simulations to show that when the quality of fit is acceptable, the fidelity of magphys estimates is independent of the degree of UV/FIR offset, with performance very similar to that previously reported for local galaxies. [ABSTRACT FROM AUTHOR]

Background Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. Methods Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72 932 siblings from UK Biobank and the Norwegian HUNT study, and summary-level data from a within-sibship Genome-wide Association Study including >140 000 individuals. Results Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant–outcome associations attenuated in the within-sibship model, but genetic variant–educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect. Conclusions These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders. [ABSTRACT FROM AUTHOR]

Negative feedback from accreting supermassive black holes is considered crucial in suppressing star formation and quenching massive galaxies. However, several models and observations suggest that black hole feedback may have a positive effect, triggering star formation by compressing interstellar medium gas to higher densities. We investigate the dual role of black hole feedback using cosmological hydrodynamic simulations from the Feedback In Realistic Environment (FIRE) project, incorporating a novel implementation of hyper-refined accretion-disc winds. Focusing on a massive, star-forming galaxy at z ∼ 2 (⁠|$M_{\rm halo} \sim 10^{12.5}\, {\rm M}_{\odot }$|⁠), we demonstrate that strong quasar winds with a kinetic power of ∼1046 erg s−1, persisting for over 20 Myr, drive the formation of a central gas cavity and significantly reduce the surface density of star formation across the galaxy's disc. The suppression of star formation primarily occurs by limiting the availability of gas for star formation rather than by evacuating the pre-existing star-forming gas reservoir (preventive feedback dominates over ejective feedback). Despite the overall negative impact of quasar winds, we identify several potential indicators of local positive feedback, including (1) the spatial anticorrelation between wind-dominated regions and star-forming clumps, (2) higher local star formation efficiency in compressed gas at the edge of the cavity, and (3) increased contribution of outflowing material to local star formation. Moreover, stars formed under the influence of quasar winds tend to be located at larger radial distances. Our findings suggest that both positive and negative AGN feedback can coexist within galaxies, although the local positive triggering of star formation has a minor influence on global galaxy growth. [ABSTRACT FROM AUTHOR]

Objectives Given the lack of accurate rapid diagnostics for urinary tract infection (UTI) in women, many countries have developed guidelines aiming to support appropriate antibiotic prescribing, but some guidelines have not been validated. We performed a diagnostic accuracy validation study of two guidelines: Public Health England (GW-1263) and Scottish Intercollegiate Guidelines Network (SIGN160). Methods We used data from women with symptoms suggestive of uncomplicated UTI from a randomized controlled trial comparing urine collection devices. Symptom information was recorded via baseline questionnaire and primary care assessment. Women provided urine samples for dipstick testing and culture. We calculated the number within each risk category of diagnostic flowcharts who had positive/mixed growth/no significant growth urine culture. Results were presented as positive/negative predictive values, with 95% CIs. Results Of women aged under 65 years, 311/509 (61.1%, 95% CI 56.7%–65.3%) classified to the highest risk category (recommended to consider immediate antibiotic prescribing) and 80/199 (40.2%, 95% CI 33.4%–47.4%) classified to the lowest risk category (recommended to reassure that UTI is less likely) by the GW-1263 guideline (n  = 810) had positive culture. For the SIGN160 guideline (n  = 814), the proportion with positive culture ranged from 60/82 (73.2%, 95% CI 62.1%–82.1%) in those for whom immediate treatment was indicated to 33/76 (43.4%, 95% CI 32.3%–55.3%) in those recommended a self-care/waiting strategy. Conclusions Clinicians should be aware of the potential for diagnostic error when using diagnostic guidelines for managing uncomplicated UTI and making antimicrobial prescribing decisions. Infection cannot be excluded on the basis of symptoms and dipstick testing alone. [ABSTRACT FROM AUTHOR]

Genetic referral for Lynch syndrome (LS) exemplifies complex clinical pathways. Identifying target behaviours (TBs) for change and associated barriers requires structured group consultation activities with busy clinicians – consolidating implementation activities whilst retaining rigour is crucial. This study aimed to: i) use process mapping to gain in-depth understandings of site-specific LS testing and referral practices in Australian hospitals and support identification of TBs for change, ii) explore if barriers to identified TBs could be identified through process mapping focus-group data, and iii) demonstrate pandemic-induced transition from in-person to virtual group interactive process mapping methods. LS clinical stakeholders attended interactive in-person or virtual focus groups to develop site-specific "process maps" visually representing referral pathways. Content analysis of transcriptions informed site-specific process maps, then clinical audit data was compared to highlight TBs for change. TBs were reviewed in follow-up focus groups. Secondary thematic analysis explored barriers to identified TBs, coded against the Theoretical Domains Framework (TDF). The transition from in-person to pandemic-induced virtual group interactive process mapping methods was documented. Process mapping highlighted six key areas of clinical practice variation across sites and site-specific TBs for change were identified. Key barriers to identified TBs emerged, categorised to seven TDF domains. Process mapping revealed variations in clinical practices surrounding LS referral between sites. Incorporating qualitative perspectives enhances process mapping by facilitating identification of TBs for change and barriers, providing a pathway to developing targeted interventions. Virtual process mapping activities produced detailed data and enabled comprehensive map development. [ABSTRACT FROM AUTHOR]

Without active galactic nucleus (AGN) feedback, simulated massive, star-forming galaxies become too compact relative to observed galaxies at z ≲ 2. In this paper, we perform high-resolution re-simulations of a massive (⁠|$M_{\star }\sim 10^{11}\, \rm {{\rm M}_{\odot }}$|⁠) galaxy at z ∼ 2.3, drawn from the Feedback in Realistic Environments (FIRE) project. In the simulation without AGN feedback, the galaxy experiences a rapid starburst and shrinking of its half-mass radius. We experiment with driving mechanical AGN winds, using a state-of-the-art hyper-Lagrangian refinement technique to increase particle resolution. These winds reduce the gas surface density in the inner regions of the galaxy, suppressing the compact starburst and maintaining an approximately constant half-mass radius. Using radiative transfer, we study the impact of AGN feedback on the magnitude and extent of the multiwavelength continuum emission. When AGN winds are included, the suppression of the compact, dusty starburst results in lowered flux at FIR wavelengths (due to decreased star formation) but increased flux at optical-to-near-IR wavelengths (due to decreased dust attenuation, in spite of the lowered star formation rate), relative to the case without AGN winds. The FIR half-light radius decreases from ∼1 to |$\sim 0.1\, \rm {kpc}$| in |$\lesssim 40\, \rm {Myr}$| when AGN winds are not included, but increases to |$\sim 2\, \rm {kpc}$| when they are. Interestingly, the half-light radius at optical-NIR wavelengths remains approximately constant over |$35\, \rm {Myr}$|⁠ , for simulations with and without AGN winds. In the case without winds, this occurs despite the rapid compaction, and is due to heavy dust obscuration in the inner regions of the galaxy. This work highlights the importance of forward-modelling when comparing simulated and observed galaxy populations. [ABSTRACT FROM AUTHOR]

therefore important to deeply characterize the human nutritional responses. Objective: Endocrine parameters and the metabolome of human plasma are rapidly responding to acute nutritional interventions such as caloric restriction or a glucose challenge. It is less well understood whether the plasma proteome would be equally dynamic, and whether it could be a source of corresponding biomarkers. Methods: We used high-throughput mass spectrometry to determine changes in the plasma proteome of i) 10 healthy, young, male individuals in response to 2 days of acute caloric restriction followed by refeeding; ii) 200 individuals of the Ely epidemiological study before and after a glucose tolerance test at 4 time points (0, 30, 60, 120 minutes); and iii) 200 random individuals from the Generation Scotland study. We compared the proteomic changes detected with metabolome data and endocrine parameters. Results: Both caloric restriction and the glucose challenge substantially impacted the plasma proteome. Proteins responded across individuals or in an individual-specific manner. We identified nutrient-responsive plasma proteins that correlate with changes in the metabolome, as well as with endocrine parameters. In particular, our study highlights the role of apolipoprotein C1 (APOC1), a small, understudied apolipoprotein that was affected by caloric restriction and dominated the response to glucose consumption and differed in abundance between individuals with and without type 2 diabetes. Conclusion: Our study identifies APOC1 as a dominant nutritional responder in humans and highlights the interdependency of acute nutritional response proteins and the endocrine system. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused severe disease in unvaccinated long-term care facility (LTCF) residents. Initial booster vaccination following primary vaccination is known to provide strong short-term protection, but data are limited on duration of protection and the protective effect of further booster vaccinations. Objective To evaluate the effectiveness of third, fourth and fifth dose booster vaccination against SARS-CoV-2 related mortality amongst older residents of LTCFs. Design Prospective cohort study. Setting LTCFs for older people in England participating in the VIVALDI study. Methods Residents aged >65 years at participating LTCFs were eligible for inclusion if they had at least one polymerase chain reaction or lateral flow device result within the analysis period 1 January 2022 to 31 December 2022. We excluded individuals who had not received at least two vaccine doses before the analysis period. Cox regression was used to estimate relative hazards of SARS-CoV-2 related mortality following 1–3 booster vaccinations compared with primary vaccination, stratified by previous SARS-CoV-2 infection and adjusting for age, sex and LTCF size (total beds). Results A total of 13,407 residents were included. Our results indicate that third, fourth and fifth dose booster vaccination provide additional short-term protection against SARS-CoV-2 related mortality relative to primary vaccination, with consistent stabilisation beyond 112 days to 45–75% reduction in risk relative to primary vaccination. Conclusions Successive booster vaccination doses provide additional short-term protection against SARS-CoV-2 related mortality amongst older LTCF residents. However, we did not find evidence of a longer-term reduction in risk beyond that provided by initial booster vaccination. [ABSTRACT FROM AUTHOR]

Introduction In 2017, NHS England introduced proactive identification of frailty into the General Practitioners (GP) contract. There is currently little information as to how this policy has been operationalised by front-line clinicians, their working understanding of frailty and impact of recognition on patient care. We aimed to explore the conceptualisation and identification of frailty by multidisciplinary primary care clinicians in England. Methods Qualitative semi-structured interviews were conducted with primary care staff across England including GPs, physician associates, nurse practitioners, paramedics and pharmacists. Thematic analysis was facilitated through NVivo (Version 12). Results Totally, 31 clinicians participated. Frailty was seen as difficult to define, with uncertainty about its value as a medical diagnosis. Clinicians conceptualised frailty differently, dependant on job-role, experience and training. Identification of frailty was most commonly informal and opportunistic, through pattern recognition of a frailty phenotype. Some practices had embedded population screening and structured reviews. Visual assessment and continuity of care were important factors in recognition. Most clinicians were familiar with the electronic frailty index, but described poor accuracy and uncertainty as to how to interpret and use this tool. There were different perspectives amongst professional groups as to whether frailty should be more routinely identified, with concerns of capacity and feasibility in the current climate of primary care workload. Conclusions Concepts of frailty in primary care differ. Identification is predominantly ad hoc and opportunistic. A more cohesive approach to frailty, relevant to primary care, together with better diagnostic tools and resource allocation, may encourage wider recognition. [ABSTRACT FROM AUTHOR]

We examine the azimuthal variations in gas-phase metallicity profiles in simulated Milky Way-mass disc galaxies from the Feedback in Realistic Environments (FIRE-2) cosmological zoom-in simulation suite, which includes a sub-grid turbulent metal mixing model. We produce spatially resolved maps of the discs at z ≈ 0 with pixel sizes ranging from 250 to 750 pc, analogous to modern integral field unit galaxy surveys, mapping the gas-phase metallicities in both the cold and dense gas and the ionized gas correlated with H  ii regions. We report that the spiral arms alternate in a pattern of metal rich and metal poor relative to the median metallicity of the order of ≲0.1 dex, appearing generally in this sample of flocculent spirals. The pattern persists even in a simulation with different strengths of metal mixing, indicating that the pattern emerges from physics above the sub-grid scale. Local enrichment does not appear to be the dominant source of the azimuthal metallicity variations at z ≈ 0: there is no correlation with local star formation on these spatial scales. Rather, the arms are moving radially inwards and outwards relative to each other, carrying their local metallicity gradients with them radially before mixing into the larger-scale interstellar medium. We propose that the arms act as freeways channeling relatively metal poor gas radially inwards, and relatively enriched gas radially outwards. [ABSTRACT FROM AUTHOR]

Background Microscopy is the gold standard for malaria diagnosis but is dependent on trained personnel. Rapid diagnostic tests (RDTs) form the mainstay of diagnosis in endemic areas without access to high-quality microscopy. We aimed to evaluate whether RDT alone could rule out imported malaria in children presenting to UK emergency departments (EDs). Methods UK-based, multi-center, retrospective, diagnostic accuracy study. Included : any child <16 years presenting to ED with history of fever and travel to a malaria-endemic country, between 01/01/2016 and 31/12/2017. Diagnosis: microscopy for malarial parasites (clinical reference standard) and RDT (index test). UK Health Research Authority approval: 20/HRA/1341. Results There were 47 cases of malaria out of 1,414 eligible cases (prevalence 3.3%) in a cohort of children whose median age was 4 years (IQR 2–9), of whom 43% were female. Cases of Plasmodium falciparum totaled 36 (77%, prevalence 2.5%). The sensitivity of RDT alone to detect malaria infection due to any Plasmodium species was 93.6% (95% CI 82.5–98.7%), specificity 99.4% (95% CI 98.9–99.7%), positive predictive value 84.6% (95% CI 71.9–93.1%) and negative predictive value 99.8% (95% CI 99.4–100.0%). Sensitivity of RDT to detect P. falciparum infection was 100% (90.3–100%), specificity 98.8% (98.1–99.3%), positive predictive value 69.2% (54.9–81.2%, n = 46/52) and negative predictive value 100% (99.7–100%, n = 1,362/1,362). Conclusions RDTs were 100% sensitive in detecting P. falciparum malaria. However, lower sensitivity for other malaria species and the rise of pfhrp2 and pfhrp3 (pfhrp2/3) gene deletions in the P. falciparum parasite mandate the continued use of microscopy for diagnosing malaria. [ABSTRACT FROM AUTHOR]

Chromosome-scale genome assemblies based on ultralong-read sequencing technologies are able to illuminate previously intractable aspects of genome biology such as fine-scale centromere structure and large-scale variation in genome features such as heterochromatin, GC content, recombination rate, and gene content. We present here a new chromosome-scale genome of the Mongolian gerbil (Meriones unguiculatus), which includes the complete sequence of all centromeres. Gerbils are thus the one of the first vertebrates to have their centromeres completely sequenced. Gerbil centromeres are composed of four different repeats of length 6, 37, 127, or 1,747 bp, which occur in simple alternating arrays and span 1–6 Mb. Gerbil genomes have both an extensive set of GC-rich genes and chromosomes strikingly enriched for constitutive heterochromatin. We sought to determine if there was a link between these two phenomena and found that the two heterochromatic chromosomes of the Mongolian gerbil have distinct underpinnings: Chromosome 5 has a large block of intraarm heterochromatin as the result of a massive expansion of centromeric repeats, while chromosome 13 is comprised of extremely large (>150 kb) repeated sequences. In addition to characterizing centromeres, our results demonstrate the importance of including karyotypic features such as chromosome number and the locations of centromeres in the interpretation of genome sequence data and highlight novel patterns involved in the evolution of chromosomes. [ABSTRACT FROM AUTHOR]

Feedback from accreting supermassive black holes (SMBHs) is thought to be a primary driver of quenching in massive galaxies, but how to best implement SMBH physics into galaxy formation simulations remains ambiguous. As part of the Feedback in Realistic Environments (FIRE) project, we explore the effects of different modelling choices for SMBH accretion and feedback in a suite of ∼500 cosmological zoom-in simulations across a wide range of halo mass (1010–1013 M⊙). Within the suite, we vary the numerical schemes for BH accretion and feedback, accretion efficiency, and the strength of mechanical, radiative, and cosmic ray feedback independently. We then compare the outcomes to observed galaxy scaling relations. We find several models satisfying observational constraints for which the energetics in different feedback channels are physically plausible. Interestingly, cosmic rays accelerated by SMBHs play an important role in many plausible models. However, it is non-trivial to reproduce scaling relations across halo mass, and many model variations produce qualitatively incorrect results regardless of parameter choices. The growth of stellar and BH mass are closely related: for example, overmassive BHs tend to overquench galaxies. BH mass is most strongly affected by the choice of accretion efficiency in high-mass haloes, but by feedback efficiency in low-mass haloes. The amount of star formation suppression by SMBH feedback in low-mass haloes is determined primarily by the time-integrated feedback energy. For massive galaxies, the 'responsiveness' of a model (how quickly and powerfully the BH responds to gas available for accretion) is an additional important factor for quenching. [ABSTRACT FROM AUTHOR]

Background The Omicron B.1.1.529 variant increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in doubly vaccinated individuals, particularly in the Oxford–AstraZeneca COVID-19 vaccine (ChAdOx1) recipients. To tackle infections, the UK's booster vaccination programmes used messenger ribonucleic acid (mRNA) vaccines irrespective of an individual's primary course vaccine type, and prioritized the clinically vulnerable. These mRNA vaccines included the Pfizer–BioNTech COVID-19 vaccine (BNT162b2) the Moderna COVID-19 vaccine (mRNA-1273). There is limited understanding of the effectiveness of different primary vaccination courses on mRNA booster vaccines against SARs-COV-2 infections and how time-varying confounders affect these evaluations. Methods Trial emulation was applied to a prospective community observational cohort in England and Wales to reduce time-varying confounding-by-indication driven by prioritizing vaccination based upon age, vulnerability and exposure. Trial emulation was conducted by meta-analysing eight adult cohort results whose booster vaccinations were staggered between 16 September 2021 and 05 January 2022 and followed until 23 January 2022. Time from booster vaccination until SARS-CoV-2 infection, loss of follow-up or end of study was modelled using Cox proportional hazard models and adjusted for age, sex, minority ethnic status, clinically vulnerability and deprivation. Results A total of 19 159 participants were analysed, with 11 709 ChAdOx1 primary courses and 7450 BNT162b2 primary courses. Median age, clinical vulnerability status and infection rates fluctuate through time. In mRNA-boosted adults, 7.4% (n  = 863) of boosted adults with a ChAdOx1 primary course experienced a SARS-CoV-2 infection compared with 7.7% (n  = 571) of those who had BNT162b2 as a primary course. The pooled adjusted hazard ratio (aHR) was 1.01 with a 95% confidence interval (CI) of: 0.90 to 1.13. Conclusion After an mRNA booster dose, we found no difference in protection comparing those with a primary course of BNT162b2 with those with a ChAdOx1 primary course. This contrasts with pre-booster findings where previous research shows greater effectiveness of BNT162b2 than ChAdOx1 in preventing infection. [ABSTRACT FROM AUTHOR]

J-domain proteins (JDPs) are critical components of the cellular protein quality control machinery, playing crucial roles in preventing the formation and, solubilization of cytotoxic protein aggregates. Bacteria, yeast, and plants additionally have large, multimeric heat shock protein 100 (Hsp100)-class disaggregases that resolubilize protein aggregates. JDPs interact with aggregated proteins and specify the aggregate-remodeling activities of Hsp70s and Hsp100s. However, the aggregate-remodeling properties of plant JDPs are not well understood. Here we identify eight orthologs of Sis1 (an evolutionarily conserved Class II JDP of budding yeast) in Arabidopsis thaliana with distinct aggregate-remodeling functionalities. Six of these JDPs associate with heat-induced protein aggregates in vivo and co-localize with Hsp101 at heat-induced protein aggregate centers. Consistent with a role in solubilizing cytotoxic protein aggregates, an atDjB3 mutant had defects in both solubilizing heat-induced aggregates and acquired thermotolerance as compared with wild-type seedlings. Next, we used yeast prions as protein aggregate models to show that the six JDPs have distinct aggregate-remodeling properties. Results presented in this study, as well as findings from phylogenetic analysis, demonstrate that plants harbor multiple, evolutionarily conserved JDPs with capacity to process a variety of protein aggregate conformers induced by heat and other stressors. [ABSTRACT FROM AUTHOR]

The UK Environment Act 2021 imposes a duty on the Secretary of State to report on 'significant' developments in environmental legislation from around the world. The analysis explores this in the context of legislation which is significant by virtue of its symbolism, rather than (or in addition to) enforceable legal content. 'Symbolic legislation' has a long history in the field of the environment, and it remains highly pertinent to today. Whilst acknowledging the constitutional dangers of symbolic legislation, the authors argue that there is something particularly compelling about the use of legislation to achieve something different from, or additional to, the enforcement of enacted rules of behaviour in environmental law. The idea that legislation can or should serve as a vehicle for the expression of values, and/or embody important moral aspirations, has traction in environmental law contexts where there is both normative and epistemic uncertainty and problems are characteristically 'hot'. [ABSTRACT FROM AUTHOR]

Chromosome rearrangements are thought to promote reproductive isolation between incipient species. However, it is unclear how often, and under what conditions, fission and fusion rearrangements act as barriers to gene flow. Here we investigate speciation between two largely sympatric fritillary butterflies, Brenthis daphne and Brenthis ino. We use a composite likelihood approach to infer the demographic history of these species from whole-genome sequence data. We then compare chromosome-level genome assemblies of individuals from each species and identify a total of nine chromosome fissions and fusions. Finally, we fit a demographic model where effective population sizes and effective migration rate vary across the genome, allowing us to quantify the effects of chromosome rearrangements on reproductive isolation. We show that chromosomes involved in rearrangements experienced less effective migration since the onset of species divergence and that genomic regions near rearrangement points have a further reduction in effective migration rate. Our results suggest that the evolution of multiple rearrangements in the B. daphne and B. ino populations, including alternative fusions of the same chromosomes, have resulted in a reduction in gene flow. Although fission and fusion of chromosomes are unlikely to be the only processes that have led to speciation between these butterflies, this study shows that these rearrangements can directly promote reproductive isolation and may be involved in speciation when karyotypes evolve quickly. [ABSTRACT FROM AUTHOR]