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Abstract Objective To review HIV testing services (HTS) costs in sub-Saharan Africa. Design A systematic literature review of studies published from January 2006 to October 2020. Methods We searched ten electronic databases for studies that reported estimates for cost per person tested ($pptested) and cost per HIV-positive person identified ($ppositive) in sub-Saharan Africa. We explored variations in incremental cost estimates by testing modality (health facility-based, home-based, mobile-service, self-testing, campaign-style, and stand-alone), by primary or secondary/index HTS, and by population (general population, people living with HIV, antenatal care male partner, antenatal care/postnatal women and key populations). All costs are presented in 2019US$. Results Sixty-five studies reported 167 cost estimates. Most reported only $pptested (90%), while (10%) reported the $ppositive. Costs were highly skewed. The lowest mean $pptested was self-testing at $12.75 (median = $11.50); primary testing at $16.63 (median = $10.68); in the general population, $14.06 (median = $10.13). The highest costs were in campaign-style at $27.64 (median = $26.70), secondary/index testing at $27.52 (median = $15.85), and antenatal male partner at $47.94 (median = $55.19). Incremental $ppositive was lowest for home-based at $297.09 (median = $246.75); primary testing $352.31 (median = $157.03); in the general population, $262.89 (median: $140.13). Conclusion While many studies reported the incremental costs of different HIV testing modalities, few presented full costs. Although the $pptested estimates varied widely, the costs for stand-alone, health facility, home-based, and mobile services were comparable, while substantially higher for campaign-style HTS and the lowest for HIV self-testing. Our review informs policymakers of the affordability of various HTS to ensure universal access to HIV testing.

Abstract The fine tuning of biological electrical signaling is mediated by variations in the rates of opening and closing of gates that control ion flux through different ion channels. Human ether-a-go-go related gene (HERG) potassium channels have uniquely rapid inactivation kinetics which are critical to the role they play in regulating cardiac electrical activity. Here, we exploit the K+ sensitivity of HERG inactivation to determine structures of both a conductive and non-conductive selectivity filter structure of HERG. The conductive state has a canonical cylindrical shaped selectivity filter. The non-conductive state is characterized by flipping of the selectivity filter valine backbone carbonyls to point away from the central axis. The side chain of S620 on the pore helix plays a central role in this process, by coordinating distinct sets of interactions in the conductive, non-conductive, and transition states. Our model represents a distinct mechanism by which ion channels fine tune their activity and could explain the uniquely rapid inactivation kinetics of HERG.

Abstract RNA-binding proteins (RBPs) have pivotal functions in RNA metabolism, but current methods are limited in retrieving RBP-RNA interactions within endogenous biological contexts. Here, we develop INSCRIBE (IN situ Sensitive Capture of RNA-protein Interactions in Biological Environments), circumventing the challenges through in situ RNA labeling by precisely directing a purified APOBEC1-nanobody fusion to the RBP of interest. This method enables highly specific RNA-binding site identification across a diverse range of fixed biological samples such as HEK293T cells and mouse brain tissue and accurately identifies the canonical binding motifs of RBFOX2 (UGCAUG) and TDP-43 (UGUGUG) in native cellular environments. Applicable to any RBP with available primary antibodies, INSCRIBE enables sensitive capture of RBP-RNA interactions from ultra-low input equivalent to ~5 cells. The robust, versatile, and sensitive INSCRIBE workflow is particularly beneficial for precious tissues such as clinical samples, empowering the exploration of genuine RBP-RNA interactions in RNA-related disease contexts.

Measurements of multiple cosmogenic nuclides in a single sample are valuable for various applications of cosmogenic nuclide exposure dating and allow for correcting exposure ages for surface weathering and erosion and establishing exposure–burial history. Here we provide advances in the measurement of cosmogenic 10Be in pyroxene and constraints on the production rate that provide new opportunities for measurements of multi-nuclide systems, such as 10Be/3He, in pyroxene-bearing samples. We extracted and measured cosmogenic 10Be in pyroxene from two sets of Ferrar Dolerite samples collected from the Transantarctic Mountains in Antarctica. One set of samples has 10Be concentrations close to saturation, which allows for the production rate calibration of 10Be in pyroxene by assuming production–decay equilibrium. The other set of samples, which has a more recent exposure history, is used to determine if a rapid fusion method can be successfully applied to samples with Holocene to Last Glacial Maximum exposure ages. From measured 10Be concentrations in the near-saturation sample set we find the production rate of 10Be in pyroxene to be 3.74 ± 0.10 atoms g−1 yr−1, which is consistent with 10Be/3He paired nuclide ratios from samples assumed to have simple exposure. Given the high 10Be concentration measured in this sample set, a sample mass of ∼ 0.5 g of pyroxene is sufficient for the extraction of cosmogenic 10Be from pyroxene using a rapid fusion method. However, for the set of samples that have low 10Be concentrations, measured concentrations were higher than expected. We attribute spuriously high 10Be concentrations to failure in removing all meteoric 10Be and/or a highly variable and poorly quantified procedural blank background correction.

Abstract Background Legumes utilize a long-distance signaling feedback pathway, termed Autoregulation of Nodulation (AON), to regulate the establishment and maintenance of their symbiosis with rhizobia. Several proteins key to this pathway have been discovered, but the AON pathway is not completely understood. Results We report a new hypernodulating mutant, defective in autoregulation, with disruption of a gene, DAR (Medtr2g450550/MtrunA17_Chr2g0304631), previously unknown to play a role in AON. The dar-1 mutant produces ten-fold more nodules than wild type, similar to AON mutants with disrupted SUNN gene function. As in sunn mutants, suppression of nodulation by CLE peptides MtCLE12 and MtCLE13 is abolished in dar. Furthermore, dar-1 also shows increased root length colonization by an arbuscular mycorrhizal fungus, suggesting a role for DAR in autoregulation of mycorrhizal symbiosis (AOM). However, unlike SUNN which functions in the shoot to control nodulation, DAR functions in the root. Conclusions DAR encodes a membrane protein that is a member of a small protein family in M. truncatula. Our results suggest that DAR could be involved in the subcellular transport of signals involved in symbiosis regulation, but it is not upregulated during symbiosis. DAR gene family members are also present in Arabidopsis, lycophytes, mosses, and microalgae, suggesting the AON and AOM may use pathway components common to other plants, even those that do not undergo either symbiosis.

Pamela J Wright, Robin M Dawson, Cynthia F Corbett Advancing Chronic Care Outcomes through Research and iNnovation (ACORN) Center, Department of Biobehavioral Health & Nursing Science, College of Nursing, University of South Carolina, Columbia, SC, USACorrespondence: Pamela J Wright, Department of Biobehavioral Health & Nursing Science, College of Nursing, University of South Carolina, 1601 Greene Street, Columbia, SC, 29208, USA, Tel +1-803-777-6039, Email wrightpamelaj@sc.eduIntroduction: Peri-postmenopausal women with the chronic condition polycystic ovary syndrome (PCOS) remain at cardiometabolic risk and/or subsist with established comorbidity while continuing to manage persistent PCOS signs and symptoms, such as hirsutism. Thus, PCOS transcends the reproductive years, yet there is sparse scientific literature on the peri-postmenopausal years of women with PCOS.Purpose: To explore how peri-postmenopausal women’s perceptions about PCOS have changed over the lifespan since their PCOS diagnosis.Methods: A cross-sectional survey with one qualitative question was conducted via Research Electronic Data Capture (REDCap) among women with PCOS aged ≥ 43 years, who were all recruited from PCOS-specific Facebook pages. Of the 107 women completing the survey, 72 substantively answered the qualitative question. The qualitative responses were analyzed using the steps of reflexive thematic analysis. Themes were interpreted and discussed through the lens of the bioecological conceptual model.Results: Respondents were 47.6 (± 4.1) years of age, primarily White (87.5%), employed full time (65.3%), and married (75%) with children (68%). Four overall themes were identified: 1) dismissal 2) information desert, 3) PCOS experience over the lifespan, and 4) mindset.Conclusion: The study findings illustrated the unique healthcare needs among peri-postmenopausal women with PCOS. Further research is needed to further explore their healthcare concerns and psychosocial needs followed by studies that develop and assess interventions that promote symptom and adaptive coping strategies across their lifespan.Keywords: polycystic ovary syndrome, systems theory, life course, women’s health

Abstract Background Respiratory Syncytial Virus (RSV) disease in young children ranges from mild cold symptoms to severe symptoms that require hospitalization and sometimes result in death. Studies have shown a statistical association between RSV subtype or phylogenic lineage and RSV disease severity, although these results have been inconsistent. Associations between variation within RSV gene coding regions or residues and RSV disease severity has been largely unexplored. Methods Nasal swabs from children (

Abstract Recent advances in machine learning (ML) have led to newer model architectures including transformers (large language models, LLMs) showing state of the art results in text generation and image analysis as well as few-shot learning (FSLC) models which offer predictive power with extremely small datasets. These new architectures may offer promise, yet the ‘no-free lunch’ theorem suggests that no single model algorithm can outperform at all possible tasks. Here, we explore the capabilities of classical (SVR), FSLC, and transformer models (MolBART) over a range of dataset tasks and show a ‘goldilocks zone’ for each model type, in which dataset size and feature distribution (i.e. dataset “diversity”) determines the optimal algorithm strategy. When datasets are small (

Phenobarbital is a long-acting barbiturate used to treat alcohol withdrawal and epilepsy. Acute overdoses present with varying levels of central nervous system depression and large overdoses can be life threatening. Phenobarbital is an attractive candidate for enhanced elimination using urinary alkalinization given it is a weak acid with a long half-life and extensive urinary elimination. Limited human data exist regarding use of urine alkalinization for the treatment of phenobarbital overdose. We present a fourteen-year-old female who was treated with urinary alkalinization alone following an intentional ingestion of 3800 mg (84.4 mg/kg) of phenobarbital tablets. Urine drugs of abuse screening was preliminary positive for barbiturates and confirmed to be phenobarbital only. The initial serum phenobarbital concentration, drawn nine hours post-ingestion, was 97.4 mcg/ml (normal range 15–40 mcg/ml). Urinary alkalinization with sodium bicarbonate was started approximately 12 h post-ingestion and stopped at 72 h post-ingestion; clinical toxicity resolved by hospital day 5. The infusion was titrated to a urinary pH of greater than 7.5. Serial serum and urine phenobarbital measurements were obtained to determine elimination half-life and urinary excretion. The elimination half-life while undergoing urinary alkalinization was 81.3 h. Prior to initiation of urinary alkalinization, the urine phenobarbital concentration was 37 mcg/ml. Approximately 8.75 h after initiation, it was greater than 200 mcg/ml at a urine pH of 8.5. Urinary alkalinization appeared to augment urinary phenobarbital excretion, though with no discernible effect on elimination half-life and unclear clinical benefit. Further research is needed to better characterize the clinical effects of urinary alkalinization for phenobarbital overdose.

Prolonged dysregulation of the autonomic nervous system (ANS) may increase propensity for physical or psychiatric illness. The current study examined differences in respiratory sinus arrhythmia (RSA) regulation in 215 adolescents with or without autism spectrum disorder (ASD) at Time 1 (T1; 10-13 years old) and 1 year later (Time 2; T2). Linear mixed effects models demonstrated lower RSA regulation in ASD, and a small interaction effect, showing blunted change in RSA from T1 to T2. Developmental differences in RSA regulation were particularly notable in females with ASD and those taking psychotropic medications. Results expand previous findings of reduced parasympathetic regulation in ASD by revealing a blunted developmental slope, indicating diagnostic differences may persist or worsen over time, particularly in females.

The acquisition of novel sexually dimorphic traits poses an evolutionary puzzle: How do new traits arise and become sex-limited? Recently acquired color vision, sexually dimorphic in animals like primates and butterflies, presents a compelling model for understanding how traits become sex-biased. For example, some Heliconius butterflies uniquely possess UV (ultraviolet) color vision, which correlates with the expression of two differentially tuned UV-sensitive rhodopsins, UVRh1 and UVRh2. To discover how such traits become sexually dimorphic, we studied Heliconius charithonia, which exhibits female-specific UVRh1 expression. We demonstrate that females, but not males, discriminate different UV wavelengths. Through whole-genome shotgun sequencing and assembly of the H. charithonia genome, we discovered that UVRh1 is present on the W chromosome, making it obligately female-specific. By knocking out UVRh1, we show that UVRh1 protein expression is absent in mutant female eye tissue, as in wild-type male eyes. A PCR survey of UVRh1 sex-linkage across the genus shows that species with female-specific UVRh1 expression lack UVRh1 gDNA in males. Thus, acquisition of sex linkage is sufficient to achieve female-specific expression of UVRh1, though this does not preclude other mechanisms, like cis-regulatory evolution from also contributing. Moreover, both this event, and mutations leading to differential UV opsin sensitivity, occurred early in the history of Heliconius. These results suggest a path for acquiring sexual dimorphism distinct from existing mechanistic models. We propose a model where gene traffic to heterosomes (the W or the Y) genetically partitions a trait by sex before a phenotype shifts (spectral tuning of UV sensitivity).

During mitosis, chromosomes assemble kinetochores to dynamically couple with spindle microtubules.1,2 Kinetochores also function as signaling hubs directing mitotic progression by recruiting and controlling the fate of the anaphase promoting complex/cyclosome (APC/C) activator CDC-20.3,4,5 Kinetochores either incorporate CDC-20 into checkpoint complexes that inhibit the APC/C or dephosphorylate CDC-20, which allows it to interact with and activate the APC/C.4,6 The importance of these two CDC-20 fates likely depends on the biological context. In human somatic cells, the major mechanism controlling mitotic progression is the spindle checkpoint. By contrast, progression through mitosis during the cell cycles of early embryos is largely checkpoint independent.7,8,9,10 Here, we first show that CDC-20 phosphoregulation controls mitotic duration in the C. elegans embryo and defines a checkpoint-independent temporal mitotic optimum for robust embryogenesis. CDC-20 phosphoregulation occurs at kinetochores and in the cytosol. At kinetochores, the flux of CDC-20 for local dephosphorylation requires an ABBA motif on BUB-1 that directly interfaces with the structured WD40 domain of CDC-20.6,11,12,13 We next show that a conserved STP motif in BUB-1 that docks the mitotic kinase PLK-114 is necessary for CDC-20 kinetochore recruitment and timely mitotic progression. The kinase activity of PLK-1 is required for CDC-20 to localize to kinetochores and phosphorylates the CDC-20-binding ABBA motif of BUB-1 to promote BUB-1-CDC-20 interaction and mitotic progression. Thus, the BUB-1-bound pool of PLK-1 ensures timely mitosis during embryonic cell cycles by promoting CDC-20 recruitment to the vicinity of kinetochore-localized phosphatase activity.

BackgroundCommunity active case finding (ACF) for tuberculosis was widely implemented in Europe and North America between 1940 and 1970, when incidence was comparable to many present-day high-burden countries. Using an interrupted time series analysis, we analysed the effect of the 1957 Glasgow mass chest X-ray campaign to inform contemporary approaches to screening.Methods and findingsCase notifications for 1950 to 1963 were extracted from public health records and linked to demographic data. We fitted Bayesian multilevel regression models to estimate annual relative case notification rates (CNRs) during and after a mass screening intervention implemented over 5 weeks in 1957 compared to the counterfactual scenario where the intervention had not occurred. We additionally estimated case detection ratios and incidence. From 11 March 1957 to 12 April 1957, 714,915 people (622,349 of 819,301 [76.0%] resident adults ≥15 years) were screened with miniature chest X-ray; 2,369 (0.4%) were diagnosed with tuberculosis. Pre-intervention (1950 to 1956), pulmonary CNRs were declining at 2.3% per year from a CNR of 222/100,000 in 1950. With the intervention in 1957, there was a doubling in the pulmonary CNR (RR: 1.95, 95% uncertainty interval [UI] [1.81, 2.11]) and 35% decline in the year after (RR: 0.65, 95% UI [0.59, 0.71]). Post-intervention (1958 to 1963) annual rates of decline (5.4% per year) were greater (RR: 0.77, 95% UI [0.69, 0.85]), and there were an estimated 4,599 (95% UI [3,641, 5,683]) pulmonary case notifications averted due to the intervention. Effects were consistent across all city wards and notifications declined in young children (0 to 5 years) with the intervention. Limitations include the lack of data in historical reports on microbiological testing for tuberculosis, and uncertainty in contributory effects of other contemporaneous interventions including slum clearances, introduction of BCG vaccination programmes, and the ending of postwar food rationing.ConclusionsA single, rapid round of mass screening with chest X-ray (probably the largest ever conducted) likely resulted in a major and sustained reduction in tuberculosis case notifications. Synthesis of evidence from other historical tuberculosis screening programmes is needed to confirm findings from Glasgow and to provide insights into ongoing efforts to successfully implement ACF interventions in today's high tuberculosis burden countries and with new screening tools and technologies.

ABSTRACT The vaginal microbiome is a key player in the etiology of spontaneous preterm birth. This study aimed to illustrate maternal environmental factors associated with vaginal microbiota composition and function in pregnancy. Women in healthy pregnancy had vaginal microbial sampling from the posterior vaginal fornix performed at 16 weeks gestation. After shotgun metagenomic sequencing, heatmaps of relative abundance data were generated. Community state type (CST) was assigned, and alpha diversity was calculated. Demography, obstetric history, well-being, exercise, and diet using food frequency questionnaires were collected and compared against microbial parameters. A total of 119 pregnant participants had vaginal metagenomic sequencing performed. Factors with strongest association with beta diversity were dietary lysine (adj-R2 0.113, P = 0.002), valine (adj-R2 0.096, P = 0.004), leucine (adj-R2 0.086, P = 0.003), and phenylalanine (adj-R2 0.085, P = 0.005, Fig. 2D). Previous vaginal delivery and breastfeeding were associated with vaginal beta diversity (adj-R2 0.048, P = 0.003; adj-R2 0.045, P = 0.004), accounting for 8.5% of taxonomy variation on redundancy analysis. Dietary fat, starch, and maltose were positively correlated with alpha diversity (fat +0.002 SD/g, P = 0.025; starch +0.002 SD/g, P = 0.043; maltose +0.440 SD/g, P = 0.013), particularly in secretor-positive women. Functional signature was associated with CST, maternal smoking, and dietary phenylalanine, accounting for 8.9%–11% of the variation in vaginal microbiome functional signature. Dietary amino acids, previous vaginal delivery, and breastfeeding history were associated with vaginal beta diversity. Functional signature of the vaginal microbiome differed with community state type, smoking, dietary phenylalanine, and vitamin K. Increased alpha diversity correlated with dietary fat and starch. These data provide a novel snapshot into the associations between maternal environment, nutrition, and the vaginal microbiome.IMPORTANCEThis secondary analysis of the MicrobeMom randomized controlled trial reveals that dietary amino acids, macronutrients, previous vaginal birth, and breastfeeding have the strongest associations with vaginal taxonomy in early pregnancy. Function of the vaginal niche is associated mainly by species composition, but smoking, vitamin K, and phenylalanine also play a role. These associations provide an intriguing and novel insight into the association between host factors and diet on the vaginal microbiome in pregnancy and highlight the need for further investigation into the complex interactions between the diet, human gut, and vaginal microbiome.

BackgroundTelomere length (TL) has been linked to cognitive function, decline and dementia. This study aimed to explore whether both measured TL and genetic disposition for TL predict dimensions of cognitive performance in a longitudinal sample of older UK adults.MethodsWe analysed data from PROTECT study participants aged ≥50 years without a dementia diagnosis, who had completed longitudinal cognitive testing. We calculated polygenic scores for telomere length (PGS-TL) for 7,877 participants and measured relative telomere length (RTL) in a subgroup of 846 participants using DNA extracted from saliva samples collected within 6 months either side of their baseline cognitive testing. Latent growth models were used to examine whether RTL and PGS-TL predict both baseline and longitudinal changes in cognitive performance (4 time-points, annually).ResultsIn the whole sample, we did not observe significant associations between either measure of telomere length and initial or longitudinal changes in cognitive performance. Stratifying by median age, in older adults (≥ ∼62 years), longer baseline RTL showed a nominal association with poorer baseline verbal reasoning performance (n = 423, Mintercept = 47.58, B = −1.05, p = .011) and PGS-TL was associated with performance over time (n = 3,939; slope factor, Mslope = 3.23, B = −0.45, p = .001; slope2 factor, Mslope2 = 0.21, B = 0.13, p = .002).ConclusionOur findings suggest either the absence of a significant relationship between telomere length (RTL and PGS-TL) and cognitive performance (baseline and change over time), or possibly a weak age-dependent and domain-specific relationship, in older adults of European ancestry. More research is needed in representative and ancestrally diverse samples over a longer assessment period. Alternative biological ageing indicators may still provide utility in the early detection of individuals at risk for cognitive decline (e.g., pace-of ageing epigenetic clocks).

This is a time of intersecting crises for young people in Scotland. More than a decade of austerity, the Covid‐19 pandemic, cost‐of‐living crisis, climate emergency, and ongoing global conflict all threaten youth security and create barriers to economic and civic participation. Alongside this, youth non‐participation is often framed as an individualised moral problem, diverting focus away from its structural causes. Evidence on youth activism suggests that young people are seeking new, creative spaces and modes of expression to challenge stigma, express dissent, and challenge inequalities in their communities. With support from grassroots youth and community organisations, youth activists can build trust, critical thinking skills, and solidarity. However, the extent to which youth activism can succeed in challenging structural causes of inequality, especially in disadvantaged neighbourhoods, requires further scrutiny. We draw on Nancy Fraser’s theory of participatory parity to explore how redistribution, recognition, and representation play out in the lives of young people, and how grassroots youth and community organisations support their development as activists. Based on a research study on the barriers and enablers to youth activism in Scotland, we seek to understand how neighbourhood‐based efforts to challenge stigma and economic inequality build dignity and hope, how relationship‐building between young people and the adults in their communities can support status recognition, and how these both contribute to emergent youth political representation.

Objective: The purpose of this study was to assess the impact of adoption of a new cardiac chest pain pathway that included hs-cTnI in the emergency department (ED) when evaluating chest pain patients. Methods: A new pathway incorporating both hs-cTnI testing (Seimens Healthineers Atellica) and risk stratification tools was developed. The impact of the new algorithm was assessed through a retrospective observational review of patients admitted to the ED with chest pain before implementation and after implementation. Before implementation, the conventional Seimens troponin Vista assay was utilized without a defined algorithmic approach. Bivariate analyses were performed comparing the time periods to determine differences in patient discharge dispositions, length of stay, outcomes, and rate of diagnostic cardiac catheterization. Results: The proportion of patients discharged from the ED increased while the proportion of patients placed in observation or admitted as in-patient decreased. Variation amongst providers regarding patient disposition decreased. The stress testing rate of patients placed in observation decreased over baseline. There was no change in 30-day MACE rate, but there was a decrease in 30-day MI rate. Conclusions: The new standardized hs-cTnI algorithm approach is safe as demonstrated by no change in 30-day MACE and is also more appropriate and efficient for patients presenting to the ED with chest pain compared to the non-standardized approach with cTnI used previously.

Background Implementation of the cardiovascular disease (CVD) prevention guidelines in the UK has been repeatedly evaluated under the auspices of the British Cardiovascular Society in three Action on Secondary and Primary Prevention by Intervention to Reduce Events (ASPIRE) surveys in 1994–1995, 2008–2010 and 2017–2019. The primary care arm of ASPIRE-2-PREVENT (A-3-P) was conducted to evaluate lifestyle and medical risk factor management in people at high risk of atherosclerotic CVD in everyday clinical practice.Methods A-3-P was a cross-sectional survey in 27 general practices and health centres across 5 English National Health Service regions. Patients with no history of atherosclerotic CVD started on blood pressure and/or lipid and/or glucose lowering treatments were identified retrospectively and interviewed at least 6 months after the initiation of medication.Results 557 patients attended the interview and examination (45.8% women; mean age 61.7±10.8 years). The risk factor control was poor: 9.3% of patients were smokers, 38.1% obese (body mass index≥30 kg/m2) and 53.5% centrally obese (waist circumference≥88 cm for women, ≥102 cm for men). Only 37.8% of patients on blood pressure-lowering therapies achieved the target of

Summary: The rapid emergence of SARS-CoV-2 variants of concern (VoC) and the threat of future zoonotic sarbecovirus spillover emphasizes the need for broadly protective next-generation vaccines and therapeutics. We utilized SARS-CoV-2 spike ferritin nanoparticle (SpFN), and SARS-CoV-2 receptor binding domain ferritin nanoparticle (RFN) immunogens, in an equine model to elicit hyperimmune sera and evaluated its sarbecovirus neutralization and protection capacity. Immunized animals rapidly elicited sera with the potent neutralization of SARS-CoV-2 VoC, and SARS-CoV-1 pseudoviruses, and potent binding against receptor binding domains from sarbecovirus clades 1b, 1a, 2, 3, and 4. Purified equine polyclonal IgG provided protection against Omicron XBB.1.5 virus in the K18-hACE2 transgenic mouse model. These results suggest that SARS-CoV-2-based nanoparticle vaccines can rapidly produce a broad and protective sarbecovirus response in the equine model and that equine serum has therapeutic potential against emerging SARS-CoV-2 VoC and diverse sarbecoviruses, presenting a possible alternative or supplement to monoclonal antibody immunotherapies.

Organizations play a central role in replicating societal inequalities. Despite theories of gendered and racialized organizations, evidence of unequal outcomes, and research on proposed mechanisms, we have few intersectional analyses demonstrating how the promotion process varies by race and gender across job levels in actual organizations. In this first-ever analysis of advancement in a U.S. firm by gender, race, and job, we run random effects logistic regression models on five years of novel longitudinal data from the software engineering workforce of a U.S.-based technology company. Results show intersectional performance-reward bias in patterns that help maintain the racialized gendered hierarchy so commonly observed in organizations: White men overrepresented at the top, women of color overrepresented at the bottom, and in the technology sector, men of Asian descent overrepresented in midlevel technical jobs and White women overrepresented in midlevel management positions. Findings suggest monitoring promotions by gender, race, and position to make visible biases that continue to impede workplace equity.

Abstract People with end‐stage kidney disease (ESKD) often exhibit impaired cardiac structure and function, which may contribute to poor exercise capacity. This study used multimodal exercise testing to investigate the central and peripheral mechanisms of exercise limitation in adults with ESKD, also comparing in‐centre hemodialysis (ICHD) to home hemodialysis (HHD). Seventeen adults (55.5 ± 14.5 years; n = 14 male; n = 12 HHD) participated. Resting cardiac examinations, followed by submaximal cycling cardiopulmonary exercise testing (CPET) and functional exercise testing, revealed cardiac structural abnormalities (increased left ventricular mass) and cardiac injury. Aerobic fitness in adults with ESKD was low, with pulmonary oxygen uptake (V̇O2) at the gas exchange threshold (GET) occuring at 39 ± 8% predicted V̇O2peak. O2 pulse, an estimate of stroke volume (SV), was higher in HHD at rest (p = 0.05, ES = 0.58) and during unloaded cycling (p = 0.05, ES = 0.58) compared to ICHD. However, thoracic bioreactance derived SV at the GET was significantly higher in adults receiving ICHD versus HHD (p = 0.01, ES = 0.74). In adults with ESKD, cardiac output was positively associated with V̇O2 at the GET (r = 0.61, p = 0.04). This study highlights prevalent exercise dysfunction in adults with ESKD undergoing dialysis, with potential distinct differences between in‐centre and home hemodialysis, mechanistically linked to underlying cardiac abnormalities.

Summary: Recent studies have found dramatic cell-type-specific responses to stimulus novelty, highlighting the importance of analyzing the cortical circuitry at this granularity to understand brain function. Although initial work characterized activity by cell type, the alterations in cortical circuitry due to interacting novelty effects remain unclear. We investigated circuit mechanisms underlying the observed neural dynamics in response to novel stimuli using a large-scale public dataset of electrophysiological recordings in behaving mice and a population network model. The model was constrained by multi-patch synaptic physiology and electron microscopy data. We found generally weaker connections under novel stimuli, with shifts in the balance between somatostatin (SST) and vasoactive intestinal polypeptide (VIP) populations and increased excitatory influences on parvalbumin (PV) and SST populations. These findings systematically characterize how cortical circuits adapt to stimulus novelty.