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Oropouche virus has recently caused outbreaks in South America and the Caribbean, expanding into areas to which the virus was previously not endemic. This geographic range expansion, in conjunction with the identification of vertical transmission and reports of deaths, has raised concerns about the broader threat this virus represents to the Americas. We review information on Oropouche virus, factors influencing its spread, transmission risk in the United States, and current status of public health response tools. On the basis of available data, the risk for sustained local transmission in the continental United States is considered low because of differences in vector ecology and in human–vector interactions when compared with Oropouche virus–endemic areas. However, more information is needed about the drivers for the current outbreak to clarify the risk for further expansion of this virus. Timely detection and control of this emerging pathogen should be prioritized to mitigate disease burden and stop its spread.

Abstract Colorectal cancer (CRC) exhibits significant genetic and epigenetic diversity, evolving into sub-clonal populations with varied metastatic potentials and treatment responses. Predicting metastatic disease in CRC patients remains challenging, underscoring the need for reliable biomarkers. While most research on therapeutic targets and biomarkers has focused on proteins, non-coding RNAs such as long non-coding RNAs (lncRNAs) comprise most of the transcriptome and demonstrate superior tissue- and cancer-specific expression. We utilised spatial transcriptomics to investigate lncRNAs in CRC tumours, offering more precise cell-type-specific expression data compared to bulk RNA sequencing. Our analysis identified 301 lncRNAs linked to malignant CRC regions, which we validated with public data. Further validation using RNA–FISH revealed three lncRNAs (LINC01978, PLAC4, and LINC01303) that are detectable in stage II tumours but not in normal epithelium and are upregulated in metastatic tissues. These lncRNAs hold potential as biomarkers for early risk assessment of metastatic disease.

West Nile virus (WNV) is the most common cause of human arboviral disease in the contiguous United States, where only lineage 1 (L1) WNV had been found. In 2023, an immunocompetent patient was hospitalized in Nebraska with West Nile neuroinvasive disease and multisystem organ failure. Testing at the Centers for Disease Control and Prevention indicated an unusually high viral load and acute antibody response. Upon sequencing of serum and cerebrospinal fluid, we detected lineage 3 (L3) and L1 WNV genomes. L3 WNV had previously only been found in Central Europe in mosquitoes. The identification of L3 WNV in the United States and the observed clinical and laboratory features raise questions about the potential effect of L3 WNV on the transmission dynamics and pathogenicity of WNV infections. Determining the distribution and prevalence of L3 WNV in the United States and any public health and clinical implications is critical.

Abstract Impaired clearance of amyloid β (Aβ) in late-onset Alzheimer’s disease (AD) affects disease progression. The role of peripheral monocytes in Aβ clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aβ-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry. Flow cytometry immunophenotyping and correlation with AD biomarkers are studied in 150 participants from the AIBL study. We also examine monocytes in human cerebrospinal fluid (CSF) and their migration in an APP/PS1 mouse model. The assay reveals macrophage-like Aβ-binding monocytes with high phagocytic potential in both the periphery and CNS. We find lower surface Aβ levels in mild cognitive impairment (MCI) and AD-dementia patients compared to cognitively unimpaired individuals. Monocyte infiltration from blood to CSF and migration from CNS to peripheral lymph nodes and blood are observed. Here we show that Aβ-binding monocytes may play a role in CNS Aβ clearance, suggesting their potential as a biomarker for AD diagnosis and monitoring.

Abstract Migratory distances and stopover locations are changing for many passerines in response to climate change. Morphological changes have been linked to rising global temperatures in both migrants and residents, but the implications of these changes on fuel loads, and associated flight ranges are little studied. Wing length and body mass changes between 1964 and 2020 were calculated for 15 migrant and partially migrant passerines in Britain. Changes in fuel load and lean body mass were also estimated and used to predict flight ranges. Twelve of the species have undergone morphological changes and eight species, estimated fuel load changes. Nine species were estimated to have reduced flight ranges, indicating that the morphological changes have not compensated fully for the reduction in flight range experienced since 1964. Partial migrants showed greater decreases in flight ranges than did full migrants, which may indicate greater behavioural plasticity in the former. Those species which do not adapt morphologically or behaviourally may be unable to complete long migrations, resulting in restriction to sub-optimal breeding/wintering habitats, or a need for a sooner first stop and more stops en route. This highlights the importance of conserving migratory stopover sites, particularly in the Mediterranean and North Africa that immediately precede major geographical barriers, as-well-as breeding and wintering grounds.

ABSTRACT: Bunching behavior in cattle may occur for several reasons including enabling social interactions, a response to stress or danger, or due to shared interest in resources such as feeding or watering areas. There is evidence in pasture grazed cattle that bunching may occur more frequently at higher ambient temperatures, possibly due to sharing of fly-load or to seek shade from the direct sun under heat stress conditions. Here we demonstrate how bunching behavior is associated with higher ambient temperatures in a barn-housed UK dairy herd. A real-time local positioning system was used, as part of a precision livestock farming (PLF) approach, to track the spatial position and activity of a commercial dairy herd (∼100 cows) in a freestall barn continuously at high temporal resolution for 4 mo between August and November 2014. Bunching was determined using 4 different spatial measures determined on an hourly basis: herd full and core range size, mean herd intercow distance (ICD), and mean herd nearest-neighbor distance (NND). For hourly mean ambient temperatures above 20°C, the herd showed higher bunching behavior with increasing ambient temperature (i.e., reduced full and core range size, ICD, and NND). Aggregated space-use intensity was found to positively correlate with localized variations in temperature across the barn (as measured by animal-mounted sensors), but the level of correlation decreased at higher ambient barn temperatures. Bunching behavior may increase localized temperatures experienced by individuals and hence may be a maladaptive behavioral response in housed dairy cattle, which are known to suffer heat stress at higher temperatures. Our study is the first to use high-resolution positional data to provide evidence of associations between bunching behavior and higher ambient temperatures for a barn-housed dairy herd in a temperate region (UK). Further studies are needed to explore the exact mechanisms for this response to inform both welfare and production management.

Abstract The leading cause of death in people living with HIV (PLWH) is cardiovascular disease, and the high prevalence of tobacco cigarette (TC) smoking is a major contributor. Switching to electronic cigarettes (ECs) has been promoted as a harm reduction strategy. We sought to determine if acute EC compared to TC smoking had less harmful effects on arrhythmogenic risk factors including acute changes in hemodynamics, heart rate variability (HRV), and ventricular repolarization (VR). In PLWH who smoke, changes in hemodynamics, HRV, and VR were compared pre/post acutely using an EC, TC, or puffing on an empty straw on different days in random order, in a crossover study. Thirty‐seven PLWH (36 males, mean age 40.5 ± 9.1 years) participated. Plasma nicotine was greater after TC versus EC use (10.12 ± 0.96 vs. 6.18 ± 0.99 ng/mL, respectively, p = 0.004). HR increased significantly, and similarly, after acute EC and TC smoking compared to control. Changes in HRV that confer increased cardiac risk (LF/HF ratio) were significantly smaller after acute EC versus TC use, consistent with a harm reduction effect. In a post‐hoc analysis of PLWH with and without positive concurrent recreational drug use as indicated by point of care urine toxicology testing, this differential effect was only seen in PLWH not currently using recreational drugs. Changes in VR were not different among the three exposures. In PLWH who smoke, EC compared to TC smoking resulted in smaller adverse changes in HRV. This differential effect was accompanied by a smaller increase in plasma nicotine, and was negated by concurrent recreational drug use. Additional studies are warranted in this vulnerable population disproportionately affected by tobacco‐related health disparities.

ABSTRACT Life depends on a conserved set of chemical energy currencies that are relics of early biochemistry. One of these is ATP, a molecule that, when paired with a divalent metal ion such as Mg2+, can be hydrolyzed to support numerous cellular and molecular processes. Despite its centrality to extant biochemistry, it is unclear whether ATP supported the function of ancient enzymes. We investigate the evolutionary necessity of ATP by experimentally reconstructing an ancestral variant of the N2-reducing enzyme nitrogenase. The Proterozoic ancestor is predicted to be ~540–2,300 million years old, post-dating the Great Oxidation Event. Growth rates under nitrogen-fixing conditions are ~80% of those of wild type in Azotobacter vinelandii. In the extant enzyme, the hydrolysis of two MgATP is coupled to electron transfer to support substrate reduction. The ancestor has a strict requirement for ATP with no other nucleotide triphosphate analogs (GTP, ITP, and UTP) supporting activity. Alternative divalent metal ions (Fe2+, Co2+, and Mn2+) support activity with ATP but with diminished activities compared to Mg2+, similar to the extant enzyme. Additionally, it is shown that the ancestor has an identical efficiency in ATP hydrolyzed per electron transferred to the extant of two. Our results provide direct laboratory evidence of ATP usage by an ancient enzyme.IMPORTANCELife depends on energy-carrying molecules to power many sustaining processes. There is evidence that these molecules may predate the rise of life on Earth, but how and when these dependencies formed is unknown. The resurrection of ancient enzymes provides a unique tool to probe the enzyme’s function and usage of energy-carrying molecules, shedding light on their biochemical origins. Through experimental reconstruction, this research investigates the ancestral dependence of a nitrogen-fixing enzyme on the energy carrier ATP, a requirement for function in the modern enzyme. We show that the resurrected ancestor does not have generalist nucleotide specificity. Rather, the ancestor has a strict requirement for ATP, like the modern enzyme, with similar function and efficiency. The findings elucidate the early-evolved necessity of energy-yielding molecules, delineating their role in ancient biochemical processes. Ultimately, these insights contribute to unraveling the intricate tapestry of evolutionary biology and the origins of life-sustaining dependencies.

We report the development of a 384-well formatted NanoBRET assay to characterize molecular glues of 14-3-3/client interactions in living cells. The seven isoforms of 14-3-3 are dimeric hub proteins with diverse roles including transcription factor regulation and signal transduction. 14-3-3 interacts with hundreds of client proteins to regulate their function and is therefore an ideal therapeutic target when client selectivity can be achieved. We have developed the NanoBRET system for three 14-3-3σ client proteins CRAF, TAZ, and estrogen receptor α (ERα), which represent three specific binding modes. We have measured stabilization of 14-3-3σ/client complexes by molecular glues with EC50 values between 100 nM and 1 μM in cells, which align with the EC50 values calculated by fluorescence anisotropy in vitro. Developing this NanoBRET system for the hub protein 14-3-3σ allows for a streamlined approach, bypassing multiple optimization steps in the assay development process for other 14-3-3σ clients. The NanoBRET system allows for an assessment of PPI stabilization in a more physiologically relevant, cell-based environment using full-length proteins. The method is applicable to diverse protein-protein interactions (PPIs) and offers a robust platform to explore libraries of compounds for both PPI stabilizers and inhibitors.

Infants less than 1 year old diagnosed with KMT2A-rearranged (KMT2A-r) acute lymphoblastic leukemia (ALL) are at high risk of remission failure, relapse, and death due to leukemia, despite intensive therapies. Infant KMT2A-r ALL blasts are characterized by DNA hypermethylation. Epigenetic priming with DNA methyltransferase inhibitors increases the cytotoxicity of chemotherapy in preclinical studies. The Children’s Oncology Group trial AALL15P1 tested the safety and tolerability of five days of azacitidine immediately prior to the start of chemotherapy on day six, in four post-induction chemotherapy courses for infants with newly diagnosed KMT2A-r ALL. The treatment was welltolerated, with only two of 31 evaluable patients (6.5%) experiencing dose-limiting toxicity. Whole genome bisulfite sequencing of peripheral blood mononuclear cells (PBMCs) demonstrated decreased DNA methylation in 87% of samples tested following five days of azacitidine. Event-free survival was similar to prior studies of newly diagnosed infant ALL. Azacitidine is safe and results in decreased DNA methylation of PBMCs in infants with KMT2A-r ALL, but the incorporation of azacitidine to enhance cytotoxicity did not impact survival. Clinicaltrials.gov identifier: NCT02828358.

Abstract Background Injuries, the leading cause of death in children 1–17 years old, are often preventable. Injury patterns are impacted by changes in the child’s environment, shifts in supervision, and caregiver stressors. The objective of this study was to evaluate the incidence and proportion of injuries, mechanisms, and severity seen in Pediatric Emergency Departments (PEDs) during the COVID-19 pandemic. Methods This multicenter, cross-sectional study from January 2019 through December 2020 examined visits to 40 PEDs for children

The 2023 European Respiratory Society Congress took place on a hybrid platform, with participants joining online and in-person in Milan, Italy. The congress welcomed over 20 000 attendees, bringing together exciting updates in respiratory science and medicine from around the world. In this article, early career members of Assembly 10 (Respiratory Infections) summarise a selection of sessions across a broad range of topics, including presentations on bronchiectasis, nontuberculous mycobacteria, tuberculosis, cystic fibrosis and coronavirus disease 2019.

Little is known about shifts in the fecal microbiome of dairy calves preceding and following the incidence of gastrointestinal disease. The objective of this cohort study was to describe the fecal microbiome of preweaned dairy calves before, during, and after gastrointestinal disease. A total of 111 Holstein dairy calves were enrolled on 2 dairies (D1 and D2) and followed until 5 weeks old. Health assessments were performed weekly and fecal samples were collected every other week. Of the 111 calves, 12 calves from D1 and 12 calves from D2 were retrospectively defined as healthy, and 7 calves from D1 and 11 calves from D2 were defined as diarrheic. Samples from these calves were sequenced targeting the 16S rRNA gene and compared based on health status within age groups and farms: healthy (0–1 week old) vs. pre-diarrheic (0–1 week old), healthy (2–3 weeks old) vs. diarrheic (2–3 weeks old), and healthy (4–5 weeks old) vs. post-diarrheic (4–5 weeks old) calves. Healthy and diarrheic samples clustered together based on age rather than health status on both farms. Based on linear discriminant analysis, a few species were identified to be differently enriched when comparing health status within age groups and farm. Among them, Bifidobacterium sp. was differently enriched in pre-diarrheic calves at D1 (0–1 week old) whereas healthy calves of the same age group and farm showed a higher abundance of Escherichia coli. Bifidobacterium sp. was identified as a biomarker of fecal samples from healthy calves (2–3 weeks old) on D1 when compared with diarrheic calves of the same age group and farm. Feces from diarrheic calves on D2 (2–3 weeks old) were characterized by taxa from Peptostreptococcus and Anaerovibrio genera whereas fecal samples of age-matched healthy calves were characterized by Collinsella aerofaciens and Bifidobacterium longum. After resolution of uncomplicated diarrhea (4–5 weeks old), Collinsella aerofaciens was more abundant in D2 calves whereas Bacteriodes uniformis was more abundant in D1 calves. Taken together, these findings suggest that the age of the preweaned calf is the major driver of changes to fecal microbiome composition and diversity even in the face of uncomplicated gastrointestinal disease.

Abstract Background People with physical disabilities (PWD) have a higher prevalence of obesity than populations without disability, but most evidence‐based weight loss programs have not included this population. The State of Slim (SOS) program is an evidence‐based weight loss program that has demonstrated success in producing weight loss in populations without disability, but it has not been adapted for or evaluated in PWD. Methods The SOS program was systematically adapted using the evidence‐informed Guidelines, Recommendations, and Adaptations Including Disability (GRAIDs) framework. A total of 35 participants enrolled in the State of Slim Everybody program. The program was offered entirely online. Body weight, attendance, and food log completion were also tracked weekly. The program length was 16.5 h and included weekly group instruction, with optional one‐on‐one sessions provided upon request. Following completion, participants completed post‐evaluation surveys on overall satisfaction with the program. The primary outcomes were program effectiveness (i.e., body weight), usability, and feasibility. Results Thirty‐two out of 35 participants completed the program, representing a retention rate of 91.4%. Average weight loss was 10.9% (9.9 ± 0.7 kg (t (31) = −13.3, p =< 0.0001)). On a 1 (dissatisfied/completely useless) to 5 (very satisfied/completely helpful) Likert scale, the average score for overall program satisfaction was 4.8 ± 0.1 and program helpfulness 4.6 ± 0.1. Conclusion The State of Slim Everybody program demonstrated significant weight loss and good usability and feasibility in PWD. Existing adaptation frameworks can be used to create inclusive health promotion programs for adults with physical disabilities.

ObjectiveEarly detection of cognitive impairment in the elderly is crucial for diagnosis and appropriate care. Brief, cost-effective cognitive screening instruments are needed to help identify individuals who require further evaluation. This study presents preliminary data on a new screening technology using automated voice recording analysis software in a Spanish population.MethodData were collected from 174 Spanish-speaking individuals clinically diagnosed as cognitively normal (CN, n = 87) or impaired (mild cognitive impairment [MCI], n = 63; all-cause dementia, n = 24). Participants were recorded performing four common language tasks (Animal fluency, alternating fluency [sports and fruits], phonemic “F” fluency, and Cookie Theft Description). Recordings were processed via text-transcription and digital-signal processing techniques to capture neuropsychological variables and audio characteristics. A training sample of 122 subjects with similar demographics across groups was used to develop an algorithm to detect cognitive impairment. Speech and task features were used to develop five independent machine learning (ML) models to compute scores between 0 and 1, and a final algorithm was constructed using repeated cross-validation. A socio-demographically balanced subset of 52 participants was used to test the algorithm. Analysis of covariance (ANCOVA), covarying for demographic characteristics, was used to predict logistically-transformed algorithm scores.ResultsMean logit algorithm scores were significantly different across groups in the testing sample (p

Abstract Two major barriers hinder the holistic understanding of subsurface critical zone (CZ) evolution and its impacts: (a) an inability to measure, define, and share information and (b) a societal structure that inhibits inclusivity and creativity. In contrast to the aboveground portion of the CZ, which is visible and measurable, the bottom boundary is difficult to access and quantify. In the context of these barriers, we aim to expand the spatial reach of the CZ by highlighting existing and effective tools for research as well as the “human reach” of CZ science by expanding who performs such science and who it benefits. We do so by exploring the diversity of vocabularies and techniques used in relevant disciplines, defining terminology, and prioritizing research questions that can be addressed. Specifically, we explore geochemical, geomorphological, geophysical, and ecological measurements and modeling tools to estimate CZ base and thickness. We also outline the importance of and approaches to developing a diverse CZ workforce that looks like and harnesses the creativity of the society it serves, addressing historical legacies of exclusion. Looking forward, we suggest that to grow CZ science, we must broaden the physical spaces studied and their relationships with inhabitants, measure the “deep” CZ and make data accessible, and address the bottlenecks of scaling and data‐model integration. What is needed—and what we have tried to outline—are common and fundamental structures that can be applied anywhere and used by the diversity of researchers involved in investigating and recording CZ processes from a myriad of perspectives.

Background: Obesity is commonly aggregated with indices of metabolic health. Proponents of body positivity approaches question whether body size is a determinant of health and well-being. Our objective was to conduct an exploratory factor analysis (EFA) to determine if body size measurements factor load with or independent of metabolic health measures. Methods: The EFA was conducted on n= 249 adults using baseline data from four weight loss trials (Sample 1: n = 40; Sample 2: n = 52; Sample 3: n = 53; Sample 4: n = 104). An EFA of nine items (systolic blood pressure [SBP], diastolic blood pressure [DBP], hemoglobin A1c [HbA1c], HDL-cholesterol [HDL], LDL-cholesterol [LDL], total cholesterol [TC], body mass index [BMI], body fat percent BF%], and waist circumference [WC]) was conducted with oblique rotation. Results: Three factors were retained, which produced a model explaining 87.5% of the variance. Six items loaded strongly (>0.8) under three components and were selected for retention (Factor 1: LDL and TC; Factor 2: BMI and WC; Factor 3: SBP and DBP). Conclusion: Body size measures loaded separately from measures of metabolic health and metabolic health were further split into lipid- and blood pressure-focused factors. These results support weight-neutral interventions to improve overall health and well-being.

In May 2021, an agricultural worker originally from Trementinal, Argentina, sought treatment for febrile illness in Tarija, Bolivia, where he resided at the time of illness onset. The patient tested negative for hantavirus RNA, but next-generation sequencing of a serum sample yielded a complete genome for Rio Negro virus.

Background In patients with atherosclerotic cardiovascular disease, increasing age is concurrently associated with higher risks of ischemic and bleeding events. The objectives are to determine the impact of aspirin dose on clinical outcomes according to age in atherosclerotic cardiovascular disease. Methods and Results In the ADAPTABLE (Aspirin Dosing: A Patient‐Centric Trial Assessing Benefits and Long‐Term Effectiveness) trial, patients with atherosclerotic cardiovascular disease were randomized to daily aspirin doses of 81 mg or 325 mg. The primary effectiveness end point was death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke. The primary safety end point was hospitalization for bleeding requiring transfusion. A total of 15 076 participants were randomized to aspirin 81 mg (n=7540) or 325 mg (n=7536) daily (median follow‐up: 26.2 months; interquartile range: 19.0–34.9 months). Median age was 67.6 years (interquartile range: 60.7–73.6 years). Among participants aged 0.05 for all). Conclusions Age does not modify the impact of aspirin dosing (81 mg or 325 mg daily) on clinical end points in secondary prevention of atherosclerotic cardiovascular disease.

BackgroundPeritoneal fluid is a medium for endometriosis-associated biomarker discovery from which the local peritoneal environment and pathophysiologic pathways are often inferred. Therefore, we evaluated the associations between peritoneal fluid color and volume at time of endometriosis-related laparoscopic surgery with patient characteristics, endometriosis type and lesion location in adolescents and young adults with endometriosis.MethodsWe conducted a cross-sectional analysis among 545 patients undergoing surgery for endometriosis who enrolled in the Women's Health Study: from Adolescence to Adulthood cohort study. Patient characteristics, surgically visualized endometriosis phenotypes, and gross characteristics of peritoneal fluid were collected in compliance with World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (EPHect) tools. Chi-square or Fisher's exact tests were applied to test for differences across categories.ResultsMost of the patients were adolescents or young adults (86% age

Selective Androgen Receptor Modulators (SARMs) are not FDA approved, and obtaining SARMs for personal use is illegal. Nevertheless, SARM use is increasingly popular amongst recreational athletes. Recent case reports of drug-induced liver injury (DILI) and tendon rupture raise serious concerns for the safety of recreational SARM users. On 10 November 2022 PubMed, Scopus, Web of Science, and ClinicalTrials.gov were searched for studies that reported safety data of SARMs. A multi-tiered screening approach was utilized, and any study or case report of generally healthy individuals exposed to any SARM was included. Thirty-three studies were included in the review with 15 case reports or case series and 18 clinical trials (total patients N = 2136 patients, exposed to SARM N = 1447). There were case reports of drug-induced liver injury (DILI) (N = 15), Achilles tendon rupture (N = 1), rhabdomyolysis (N = 1), and mild reversible liver enzyme elevation (N = 1). Elevated alanine aminotransferase (ALT) was commonly reported in clinical trials in patients exposed to SARM (mean 7.1% across trials). Two individuals exposed to GSK2881078 in a clinical trial were reported to have rhabdomyolysis. Recreational SARM use should be strongly discouraged, and the risks of DILI, rhabdomyolysis, and tendon rupture should be emphasized. However, despite warnings, if a patient refuses to discontinue SARM use, ALT monitoring or dose reduction may improve early detection and prevention of DILI.

Abstract Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

In 2020, Montana, USA, reported a large increase in Colorado tick fever (CTF) cases. To investigate potential causes of the increase, we conducted a case–control study of Montana residents who tested positive or negative for CTF during 2020, assessed healthcare providers’ CTF awareness and testing practices, and reviewed CTF testing methods. Case-patients reported more time recreating outdoors on weekends, and all reported finding a tick on themselves before illness. No consistent changes were identified in provider practices. Previously, only CTF serologic testing was used in Montana. In 2020, because of SARS-CoV-2 testing needs, the state laboratory sent specimens for CTF testing to the Centers for Disease Control and Prevention, where more sensitive molecular methods are used. This change in testing probably increased the number of CTF cases detected. Molecular testing is optimal for CTF diagnosis during acute illness. Tick bite prevention measures should continue to be advised for persons doing outdoor activities.

The 2019–2020 Australian bushfire season had a devastating impact on native wildlife. It was estimated that 3 billion native animals were impacted by the fires, yet there are few estimates of the number of animals that were rescued and rehabilitated post-fire. Focusing on the state of New South Wales (NSW) and Kangaroo Island, South Australia, we used a case study approach to determine the number of marsupials that were reported rescued due to the 2019–2020 bushfires in these areas and analysed species-specific trends in rescue and release success. In NSW, we found 889 reports of fire-affected marsupials in 2019–2020, mostly comprising kangaroos and wallabies (macropods; n = 458), koalas (n = 204), and possums (n = 162), with a smaller number of wombats (n = 43) and other marsupial species. Most reports of fire-affected marsupials occurred 6–8 weeks after fire ignition, and there was no difference in temporal frequency of rescues between marsupial groups. For the three main groups, the probability of survival and subsequent release differed, with macropods having the lowest probability of release after rescue (0.15 ± 0.04) compared to koalas (0.47 ± 0.04) and possums (0.55 ± 0.10). The type of injury was the main predictor of survival during rehabilitation for all three marsupial groups, with those malnourished/moribund or with traumatic injuries less likely to survive rehabilitation. Death or euthanasia occurred on the day of rescue for 77% of macropods, 48% of possums and 15% of koalas. Koalas most often died during rehabilitation rather than on the day of rescue, with 73% either dying or being euthanised between day 1 and 30 post-rescue, representing a potential welfare concern. On Kangaroo Island, koalas were the most frequently rescued marsupial species; most euthanasia cases and deaths occurred in a hospital, whereas other marsupials were mostly euthanised at triage. In both jurisdictions, koalas were over-represented while possums were under-represented relative to baseline population densities and wildlife rescue trends in the years before the 2019–2020 bushfires. These species differences in presentation post-fire warrant further investigation, as do the differences in triage, survival and release outcomes. It is hypothesised that the high intensity and large scale of the 2019–2020 fires impeded marsupial fire evasion tactics, as evidenced by the small number of animals found for rescue, and the differing rates of presentation relative to underlying population densities for the main marsupial groups. Based on our findings, there is a need for detailed record keeping and data sharing, development of consistent and evidence-based triage, treatment and euthanasia guidelines and deployment of trained wildlife emergency rescue teams with advanced search techniques to minimise animal suffering where safe to do so.

ABSTRACT California serogroup viruses (CSGVs) of medical importance in the United States include La Crosse virus, Jamestown Canyon virus (JCV), California encephalitis virus, and snowshoe hare virus. Current diagnosis of CSGVs relies heavily on serologic techniques for detecting immunoglobulin M (IgM), an indication of a recent CSGV infection. However, human-positive control sera reactive to viruses in the serogroup are scarce because detection of recent infections is rare. Here, we describe the development of new murine monoclonal antibodies (MAbs) reactive to CSGVs and the engineering of a human-murine chimeric antibody by combining the variable regions of the broadly CSGV cross-reactive murine MAb, 3-3B6/2-3B2 and the constant region of the human IgM. MAb 3-3B6/2-3B2 recognizes a tertiary epitope on the Gn/Gc heterodimer, and epitopes important in JCV neutralization were mapped to the Gc glycoprotein. This engineered human IgM constitutively expressed in a HEK-293 stable cell line can replace human-positive control sera in diagnostic serological techniques such as IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). Compared to the parent murine MAbs, the human-chimeric IgM antibody had identical serological activity to CSGVs in ELISA and demonstrated equivalent reactivity compared to human immune sera in the MAC-ELISA. Importance Orthobunyaviruses in the California serogroup cause severe neurological disease in children and adults. While these viruses are known to circulate widely in North America, their occurrence is rare. Serological testing for CSGVs is hindered by the limited availability and volumes of human-positive specimens needed as controls in serologic assays. Here, we described the development of a murine monoclonal antibody cross-reactive to CSGVs engineered to contain the variable regions of the murine antibody on the backbone of human IgM. The chimeric IgM produced from the stably expressing HEK293 cell line was evaluated for use as a surrogate human-positive control in a serologic diagnostic test.

Highly effective cystic fibrosis (CF) transmembrane conductance regulator (CFTR) modulator therapies (HEMT), including elexacaftor-tezacaftor-ivacaftor, correct the underlying molecular defect causing CF. HEMT decreases general symptom burden by improving clinical metrics and quality of life for most people with CF (PwCF) with eligible CFTR variants. This has resulted in more pregnancies in women living with CF. All HEMT are known to be able pass through the placenta and into breast milk in mothers who continue on this therapy while pregnant and breast feeding. Toxicity studies of HEMT in young rats demonstrated infant cataracts, and case reports have reported the presence of congenital cataracts in early life exposure to HEMT. This article reviews the evidence for how HEMT influences the dynamic and interdependent processes of healthy and abnormal lens development in the context of HEMT exposure during pregnancy and breastfeeding, and raises questions that remain unanswered.

Abstract Introduction Many barriers prevent individuals from regularly engaging in physical activity (PA), including lack of time and access to facilities. Providing free gym membership close to one's work may alleviate both time and financial barriers, increase PA, and result in greater weight loss. The purpose of this secondary analysis was to determine if gym usage, self‐reported leisure PA, and weight loss differed between participants working on the University of Colorado Anschutz Medical Campus (ON) versus working off‐campus (OFF) during a 6‐month weight loss trial. Methods 117 adults (ON, n = 62; OFF, n = 55) with overweight or obesity received free gym memberships for the duration of trial. Average gym check ins/week, self‐report leisure PA, weight, and fat and lean mass were compared between groups. Results ON reported more check‐ins than OFF (ON, 0.93 ± 0.16 times/week; OFF, 0.55 ± 0.10 times/week p = 0.038). Both groups reported increased leisure PA, with ON reporting more leisure PA than OFF at month 4. Both groups had reductions in weight and fat mass, which were similar between groups. Conclusion Gym usage in both groups was low, suggesting that convenient and free gym access only marginally promoted use of provided facilities, likely having little additional impact on PA and weight change. CLINICAL TRIAL REGISTRATION The parent trial was registered at clinicaltrials.gov: NCT02627105.

IgG4-related disease (IgG4-RD) is an immune-mediated multiorgan fibroinflammatory disorder with variable clinical presentations. IgG4-RD cardiovascular involvement is considered rare, with pulmonary arterial involvement reported in a small subset of cases. Known pulmonary artery manifestations include pulmonary arteritis, pulmonary artery stenoses and central pulmonary artery aneurysms. Here we report 2 different patients with multifocal dilatation of the segmental and subsegmental pulmonary arteries with differing degrees of severity. Both patients also had coronary arterial abnormalities.

Abstract Understanding the severity and extent of near surface critical zone (CZ) disturbances and their ecosystem response is a pressing concern in the face of increasing human and natural disturbances. Predicting disturbance severity and recovery in a changing climate requires comprehensive understanding of ecosystem feedbacks among vegetation and the surrounding environment, including climate, hydrology, geomorphology, and biogeochemistry. Field surveys and satellite remote sensing have limited ability to effectively capture the spatial and temporal variability of disturbance and CZ properties. Technological advances in remote sensing using new sensors and new platforms have improved observations of changes in vegetation canopy structure and productivity; however, integrating measures of forest disturbance from various sensing platforms is complex. By connecting the potential for remote sensing technologies to observe different CZ disturbance vectors, we show that lower severity disturbance and slower vegetation recovery are more difficult to quantify. Case studies in montane forests from the western United States highlight new opportunities, including evaluating post‐disturbance forest recovery at multiple scales, shedding light on understory vegetation regrowth, detecting specific physiological responses, and refining ecohydrological modeling. Learning from regional CZ disturbance case studies, we propose future directions to synthesize fragmented findings with (a) new data analysis using new or existing sensors, (b) data fusion across multiple sensors and platforms, (c) increasing the value of ground‐based observations, (d) disturbance modeling, and (e) synthesis to improve understanding of disturbance.

Background Internet‐based participation has the potential to enhance pragmatic and decentralized trials, where representative study populations and generalizability to clinical practice are key. We aimed to study the differences between internet and noninternet/telephone participants in a large remote, pragmatic trial. Methods and Results In a subanalysis of the ADAPTABLE (Aspirin Dosing: A Patient‐Centric Trial Assessing Benefits and Long‐Term Effectiveness) study, we compared internet participants with those who opted for noninternet participation. Study process measures examined included participant characteristics at consent, study medication adherence, and study retention. The clinical outcome examined was a composite of all‐cause mortality, hospitalization for myocardial infarction, or hospitalization for stroke. Noninternet participants were older (mean 69.4 versus 67.4 years), more likely to be female (38.9% versus 30.2%), more likely to be Black (27.3% versus 6.0%) or Hispanic (11.1% versus 2.0%), and had a higher number of comorbid conditions. The composite clinical outcome was more than twice as high in noninternet participants. The hazard of nonadherence to the assigned aspirin dosage was 46% higher in noninternet participants than internet participants. Conclusions Noninternet participants differed from internet participants in notable demographic characteristics while having poorer baseline health. Over the course of ADAPTABLE, they also had worse clinical outcomes and greater likelihood of study drug nonadherence. These results suggest that trials focused on internet participation select for younger, healthier participants with a higher proportion of traditionally overrepresented patients. Allowing noninternet participation enhances diversity; however, additional steps may be needed to promote study retention and study medication adherence. Registration Information clinicaltrials.gov. Identifier: NCT02697916.

Herpes simplex virus type 2 (HSV-2) coinfection is associated with increased HIV-1 viral loads and expanded tissue reservoirs, but the mechanisms are not well defined. HSV-2 recurrences result in an influx of activated CD4+ T cells to sites of viral replication and an increase in activated CD4+ T cells in peripheral blood. We hypothesized that HSV-2 induces changes in these cells that facilitate HIV-1 reactivation and replication and tested this hypothesis in human CD4+ T cells and 2D10 cells, a model of HIV-1 latency. HSV-2 promoted latency reversal in HSV-2–infected and bystander 2D10 cells. Bulk and single-cell RNA-Seq studies of activated primary human CD4+ T cells identified decreased expression of HIV-1 restriction factors and increased expression of transcripts including MALAT1 that could drive HIV replication in both the HSV-2–infected and bystander cells. Transfection of 2D10 cells with VP16, an HSV-2 protein that regulates transcription, significantly upregulated MALAT1 expression, decreased trimethylation of lysine 27 on histone H3 protein, and triggered HIV latency reversal. Knockout of MALAT1 from 2D10 cells abrogated the response to VP16 and reduced the response to HSV-2 infection. These results demonstrate that HSV-2 contributes to HIV-1 reactivation through diverse mechanisms, including upregulation of MALAT1 to release epigenetic silencing.

Drought monitoring and early detection have improved greatly in recent decades through the development and refinement of numerous indices and indicators. However, a lack of guidance, based on user experience, exists as to which drought-monitoring tools are most appropriate in a given location. This review paper summarizes the results of targeted user engagement and the published literature to improve the understanding of drought across North America and to enhance the utility of drought-monitoring tools. Workshops and surveys were used to assess and make general conclusions about the perceived performance of drought indicators, indices and impact information used for monitoring drought in the five main Köppen climate types (Tropical, Temperate, Continental, Polar Tundra, Dry) found across Canada, Mexico, and the United States. In Tropical, humid Temperate, and southerly Continental climates, droughts are perceived to be more short-term (less than 6 months) in duration rather than long-term (more than 6 months). In Polar Tundra climates, Dry climates, Temperate climates with dry warm seasons, and northerly Continental climates, droughts are perceived to be more long-term than short-term. In general, agricultural and hydrological droughts were considered to be the most important drought types. Drought impacts related to agriculture, water supply, ecosystem, and human health were rated to be of greatest importance. Users identified the most effective indices and indicators for monitoring drought across North America to be the U.S. Drought Monitor (USDM) and Standardized Precipitation Index (SPI) (or another measure of precipitation anomaly), followed by the Normalized Difference Vegetation Index (NDVI) (or another satellite-observed vegetation index), temperature anomalies, crop status, soil moisture, streamflow, reservoir storage, water use (demand), and reported drought impacts. Users also noted the importance of indices that measure evapotranspiration, evaporative demand, and snow water content. Drought indices and indicators were generally thought to perform equally well across seasons in Tropical and colder Continental climates, but their performance was perceived to vary seasonally in Dry, Temperate, Polar Tundra, and warmer Continental climates, with improved performance during warm and wet times of the year. The drought indices and indicators, in general, were not perceived to perform equally well across geographies. This review paper provides guidance on when (time of year) and where (climate zone) the more popular drought indices and indicators should be used. The paper concludes by noting the importance of understanding how drought, its impacts, and its indicators are changing over time as the climate warms and by recommending ways to strengthen the use of indices and indicators in drought decision making.

Abstract Background There are well‐established regional differences in obesity prevalence in the United States but relatively little is known about why or whether success in weight loss differs regionally. Objective The objective of this study was to determine whether changes in body weight, engagement in physical activity (PA), and psychosocial factors differed in Alabama (AL) versus Colorado (CO) in response to a 16‐week behavioral weight loss program. Design This is an ancillary study to a weight loss intervention being conducted simultaneously in AL and CO with identical intervention content and delivery in 70 participants (n = 31 AL and n = 39 CO). Body weight, objective (accelerometry) PA, and responses to psychosocial questionnaires (reward‐based eating, stress, social support) were collected at baseline and at Week 16. Results There were no differences in percent weight loss between states (AL: 10.98%; CO: 11.675%, p = 0.70), and weights at Week 16 were not different for participants in AL and CO (AL: 101.54 ± 4.39 kg, CO: 100.42 ± 3.67 kg, p = 0.84). Accelerometry‐derived step count, stepping time, and activity score were all greater at Week 16 for participants in AL compared to participants in CO. Hedonic eating scores were more favorable for participants in AL at baseline (AL: 24.08 ± 2.42; CO: 34.99 ± 2.12, p = 0.0023) and at Week 16 (AL: 18.62 ± 2.70; CO: 29.11 ± 2.19, p = 0.0023). Finally, participants in AL presented more favorable social support scores at Week 16 compared to participants in CO. Conclusions Weight loss did not differ between states, suggesting that factors contributing to higher obesity rates in some regions of the United States may not be barriers to weight loss. Further, participants in AL experienced greater improvements in some factors associated with weight maintenance, indicating the need to study regional differences in weight loss maintenance. National Clinical Trial 03832933.

The European Respiratory Society International Congress took place both in person, in Barcelona, Spain, and online in 2022. The congress welcomed over 19 000 attendees on this hybrid platform, bringing together exciting updates in respiratory science and medicine from around the world. In this article, Early Career Members of the Respiratory Infections Assembly (Assembly 10) summarise a selection of sessions across a broad range of topics, including presentations on bronchiectasis, nontuberculous mycobacteria, tuberculosis, cystic fibrosis and coronavirus disease 2019.

Sex steroid hormones are powerful regulators of reproductive behavior and physiology in vertebrates, and steroidogenesis has distinct sex- and season-specific patterns ultimately dictated by the expression of key enzymes. Most comparative endocrinology studies, however, focus only on circulating levels of sex steroids to determine their temporal association with life-history events in what are termed associated reproductive patterns. The red-sided garter snake (Thamnophis sirtalis parietalis) is a notable exception; this species exhibits maximal sex behavior decoupled from maximal sex steroid production and gametogenesis in what is termed a dissociated reproductive pattern. And while this is true for male red-sided garter snakes and their production of testosterone, females have maximal estradiol production during peak breeding (spring) but only immediately after mating. Here, we demonstrate that expression of ovarian aromatase (conversion of androgens to estrogens) matches the established seasonal hormone pattern in females. Additionally, steroidogenic gene expression in the ovary is broadly reduced if not suppressed compared to the testis throughout the active year. Bizarrely, male red-sided garter snakes demonstrate an unexplained pattern of steroidogenic gene expression in the testis. StAR (import of cholesterol to steroidogenesis) is maximally expressed in spring, yet Hsd17b3 expression (conversion of androstenedione to testosterone) is highest in summer, with the latter matching the established summer peak in male testosterone. The function of elevated StAR in spring is unknown, but our results suggest a decoupling between maximal StAR expression and testosterone biosynthesis (Hsd17b3 expression). We also purport that the reproductive pattern binary should be reassessed given its lack of fit for many vertebrate species that demonstrate seasonal, mixed patterns of (a)synchrony between circulating sex hormones and reproductive behavior.

Abstract Background Corneal immune cells interact with corneal sensory nerves during both homeostasis and inflammation. This study sought to evaluate temporal changes to corneal immune cell density in a mouse model of epithelial abrasion and nerve injury, and to investigate the immunomodulatory effects of topical decorin, which we have shown previously to promote corneal nerve regeneration. Methods Bilateral corneal epithelial abrasions (2 mm) were performed on C57BL/6J mice. Topical decorin or saline eye drops were applied three times daily for 12 h, 24 h, 3 days or 5 days. Optical coherence tomography imaging was performed to measure the abrasion area. The densities of corneal sensory nerves (β-tubulin III) and immune cells, including dendritic cells (DCs; CD11c+), macrophages (Iba-1+) and neutrophils (NIMP-R14+) were measured. Cx3cr1gfp/gfp mice that spontaneously lack resident corneal intraepithelial DCs were used to investigate the specific contribution of epithelial DCs. Neuropeptide and cytokine gene expression was evaluated using qRT-PCR at 12 h post-injury. Results In decorin-treated corneas, higher intraepithelial DC densities and lower neutrophil densities were observed at 24 h after injury, compared to saline controls. At 12 h post-injury, topical decorin application was associated with greater re-epithelialisation. At 5 days post-injury, corneal stromal macrophage density in the decorin-treated and contralateral eyes was lower, and nerve density was higher, compared to eyes treated with saline only. Lower expression of transforming growth factor beta (TGF-β) and higher expression of CSPG4 mRNA was detected in corneas treated with topical decorin. There was no difference in corneal neutrophil density in Cx3cr1gfp/gfp mice treated with or without decorin at 12 h. Conclusions Topical decorin regulates immune cell dynamics after corneal injury, by inhibiting neutrophils and recruiting intraepithelial DCs during the acute phase (

Mechanisms that explain behavior change within web-based lifestyle interventions are not well-studied. This secondary analysis explores whether the effects of the DUET web-based lifestyle intervention on diet, physical activity, and/or adiposity are mediated through changes in self-efficacy, social support, and perceived barriers (key constructs of social cognitive theory). Data on mediators, diet quality, caloric intake, moderate-to-vigorous physical activity (MVPA), weight, and waist circumference (WC) were analyzed from 112 cancer survivors and their partners enrolled in the DUET intervention. Mediation analyses were performed using Mplus to execute regression analyses and determine associations. Mediation analyses supported an effect of the intervention on caloric intake (−3.52, 95% CI [−8.08 to −0.84]), weight (−1.60, CI [−3.84 to −0.47]), and WC (−0.83, CI [−1.77 to −0.18]), interpreting these negative associations as intervention induced reductions in dietary barriers. Higher social support was significantly and positively associated with, but not a mediator for, improvements in self-reported and accelerometry-measured MVPA (b = 0.69, CI [0.19, 1.24]) and (b = 0.55, CI [0.15, 1.00]), respectively. Self-efficacy did not appear to mediate the intervention’s effects. Findings suggest that the effects of the DUET intervention on diet and adiposity stem from reducing perceived barriers to a healthful, low-calorie diet.

ObjectiveValidate the performance characteristics of two analyte specific, laboratory developed tests (LDTs) for the quantification of SARS-CoV-2 subgenomic RNA (sgRNA) and viral load on the Hologic Panther Fusion® using the Open Access functionality.MethodsCustom-designed primers/probe sets targeting the SARS-CoV-2 Envelope gene (E) and subgenomic E were optimized. A 20-day performance validation following laboratory developed test requirements was conducted to assess assay precision, accuracy, analytical sensitivity/specificity, lower limit of detection and reportable range.ResultsQuantitative SARS-CoV-2 sgRNA (LDT-Quant sgRNA) assay, which measures intermediates of replication, and viral load (LDT-Quant VLCoV) assay demonstrated acceptable performance. Both assays were linear with an R2 and slope equal to 0.99 and 1.00, respectively. Assay precision was evaluated between 4-6 Log10 with a maximum CV of 2.6% and 2.5% for LDT-Quant sgRNA and LDT-Quant VLCoV respectively. Using negative or positive SARS-CoV-2 human nasopharyngeal swab samples, both assays were accurate (kappa coefficient of 1.00 and 0.92). Common respiratory flora and other viral pathogens were not detected and did not interfere with the detection or quantification by either assay. Based on 95% detection, the assay LLODs were 729 and 1206 Copies/mL for the sgRNA and VL load LDTs, respectively.ConclusionThe LDT-Quant sgRNA and LDT-Quant VLCoV demonstrated good analytical performance. These assays could be further investigated as alternative monitoring assays for viral replication; and thus, medical management in clinical settings which could inform isolation/quarantine requirements.

Bovine respiratory disease (BRD) is a leading cause of calf morbidity and mortality, and prevalence remains high despite current management practices. Differential gene expression (DGE) provides detailed insight into individual immune responses and can illuminate enriched pathways and biomarkers that contribute to disease susceptibility and outcomes. The aims of this study were to investigate differences in peripheral leukocyte gene expression in Holstein preweaned heifer calves 1) with and without BRD, and 2) across weeks of age. Calves were enrolled for this short-term longitudinal study on two commercial dairies in Washington State. Calves were assessed every two weeks throughout the pre-weaning period using clinical respiratory scoring (CRS) and thoracic ultrasonography (TUS), and blood samples were collected. Calves were selected that were either healthy (n = 10) or had BRD diagnosed by CRS (n = 7), TUS (n = 6), or both (n = 6) in weeks 5 or 7 of life). Three consecutive time point samples were analyzed for each BRD calf consisting of PRE, ONSET, and POST samples. Nineteen genes of interest were selected based on previous gene expression studies in cattle: ALOX15, BPI, CATHL6, CXCL8, DHX58, GZMB, HPGD, IFNG, IL17D, IL1R2, ISG15, LCN2, LIF, MX1, OAS2, PGLYRP1, S100A8, SELP, and TNF. Comparisons were made between age and disease time point matched BRD and healthy calves as well as between calf weeks of age. No DGE was observed between diseased and healthy calves; however, DGE was observed between calf weeks of age regardless of disease state. Developmental differences in leukocyte gene expression, phenotype, and functionality make pre-weaned calves immunologically distinct from mature cattle, and early life shifts in calf leukocyte populations likely contribute to the age-related gene expression differences we observed. Age overshadows disease impacts to influence gene expression in young calves, and immune development progresses upon a common trajectory regardless of disease during the preweaning period.

IntroductionFemale cancer survivors who received gonadotoxic cancer treatment are at risk for profound diminished ovarian reserve and/or primary ovarian insufficiency with resulting infertility, which can be associated with distress and decreased quality of life.. Despite prioritizing future parenthood, many survivors are unsure of the impact of their treatment on their future fertility, and little is known about the perceived reproductive health needs and factors associated with receipt of a fertility status assessment (FSA). There is a lack of developmentally appropriate reproductive health decisional support interventions available for emerging adult cancer survivors. This study will explore the perceived reproductive health needs of emerging adult female survivors of childhood cancer and to identify decisional and contextual factors that influence pursuit of FSA using an explanatory sequential quantitative to qualitative mixed methods design.Methods and analysisThis study will enroll 325 female survivors (aged 18 to 29 years and >1-year post treatment; diagnosed with cancer < age 21 years) from four cancer centers in the United States. Sociodemographic and developmental factors, reproductive knowledge and values, decisional needs, and receipt of an FSA will be assessed through a web-based survey. Informed by survey findings, a subset of participants will be recruited for qualitative interviews to explore decisional factors associated with uptake of an FSA. Clinical data will be abstracted from the medical records. Multivariable logistic regression models will be developed to identify factors associated with FSA and qualitative descriptive analysis will be used to develop themes from the interviews. Quantitative and qualitative findings will be merged using a joint display to develop integrated study conclusions and direct future interventional research.

The National Criticality Experiments Research Center (NCERC) located at the Nevada National Security Site (NNSS) in the Device Assembly Facility (DAF) and operated by Los Alamos National Laboratory (LANL) is the only general purpose critical experiments facility in the United States. Experiments from subcritical to critical and above prompt critical are carried out at NCERC on a regular basis. In recent years, NCERC has become more involved in experiments related to nuclear energy, including the Kilopower/KRUSTY demonstration and the recent Hypatia experiment. Multiple nuclear energy related projects are currently ongoing at NCERC. This paper discusses NCERC’s role in advanced reactor design and how that role may change in the future.

[This corrects the article DOI: 10.1371/journal.pntd.0010487.].

Purpose Caring for critically ill patients requires non-technical skills such as teamwork, communication, and task management. The Behaviorally Anchored Rating Scale (BARS) is a brief tool used to assess non-technical skills. The investigators determined inter- and intra-rater reliability of the BARS when used to assess medical students in simulated scenarios.Method The investigators created simulation scenarios for medical students during their pediatric clerkship. Content experts reviewed video recordings of the simulations and assigned BARS scores for four performance components (Situational Awareness, Decision-Making, Communication, and Teamwork) for the leader and for the team as a whole. Krippendorff’s alpha with ordinal difference was calculated to measure inter- and intra-rater reliability.Results Thirty medical students had recordings available for review. Inter- and intra-rater reliability for performance components were, respectively, Individual Situational Awareness (0.488, 0.638), Individual Decision-Making (0.529, 0.691), Individual Communication (0.347, 0.473), Individual Teamwork (0.414, 0.466), Team Situational Awareness (0.450, 0.593), Team Decision Making (0.423, 0.703), Team Communication (0.256, 0.517), and Team Teamwork (0.415, 0.490).Conclusions The BARS demonstrated limited reliability when assessing medical students during their pediatric clerkship. Given the unique needs of this population, a modified or new objective scoring system for assessing non-technical skills may be needed for medical students.

COVID-19 drastically changed many aspects of life in the U.S. and most certainly changed standard operating procedures in higher education. Moving all classes completely online created numerous challenges not only for students, but also for faculty. For students, these challenges included issues related to physical and mental health, job loss, and caregiving, as well as access to internet and even access to a home computer. Faculty also faced challenges. For example, many colleges and universities rely on adjunct faculty who are compensated on a course-by-course basis. Although most institutions provided faculty development sessions to make a smooth transition to online teaching, adjunct faculty were not necessarily invited to participate and, when they were, they were not compensated for time spent in these sessions or the additional work incurred to transition and teach in the online environment. This essay explores how community college students and faculty in the basic course responded to the COVID-19 crisis. Specifically, we discuss issues of employment, family responsibilities, and the digital divide as they reveal systemic inequities in the college setting, as well as in society.

Biogeochemical properties of soils play a crucial role in soil and stream chemistry throughout a watershed. How water interacts with soils during subsurface flow can have impacts on water quality, thus, it is fundamental to understand where and how certain soil water chemical processes occur within a catchment. In this study, ~200 soil samples were evaluated throughout a small catchment in the Front Range of Colorado, USA to examine spatial and vertical patterns in major soil solutes among different landscape units: riparian areas, alluvial/colluvial fans, and steep hillslopes. Solutes were extracted from the soil samples in the laboratory and analyzed for major cation (Li, K, Mg, Br, and Ca) and anion (F, Cl, NO2, NO3, PO4, and SO4) concentrations using ion chromatography. Concentrations of most solutes were greater in near surface soils (10 cm) than in deeper soils (100 cm) across all landscape units, except for F which increased with depth, suggestive of surface accumulation processes such as dust deposition or enrichment due to biotic cycling. Potassium had the highest variation between depths, ranging from 1.04 mg/l (100 cm) to 3.13 mg/l (10 cm) sampled from riparian landscape units. Nearly every solute was found to be enriched in riparian areas where vegetation was visibly denser, with higher mean concentrations than the hillslopes and fans, except for NO3 which had higher concentrations in the fans. Br, NO2, and PO4 concentrations were often below the detectable limit, and Li and Na were not variable between depths or landscape units. Ratioed stream water concentrations (K:Na, Ca:Mg, and NO3:Cl) vs. discharge relationships compared to the soil solute ratios indicated a hydraulic disconnection between the shallow soils (

Abstract Amygdala activity in context of the splenocardiac model has not been investigated in healthy, young adults and has not been compared between nonsmokers, electronic cigarette users, and smokers. The purpose of the current study was to determine whether fluorodeoxyglucose positron emission tomography/computer tomography (FDG PET/CT) scans would demonstrate positively correlated metabolic activity in the amygdala, bone marrow, spleen, and aorta, elucidating activation of the splenocardiac axis in otherwise healthy young people who use tobacco products compared to nonusers. Moreover, the study was conducted to evaluate whether electronic cigarette users and tobacco smokers have similar levels of inflammation compared to nonusers. In 45 healthy adults (mean age = 25 years), including nonsmoker (n = 15), electronic cigarette user (n = 16), and smoker (n = 14) groups, metabolic activity in the amygdala, spleen, aorta, bone marrow of thoracic vertebrae, and adjacent erector spinae skeletal muscle was quantified through visualization of radioactive glucose (18FDG) uptake by FDG‐PET/CT. The maximum standardized uptake value for each region was calculated for correlation analyses and comparisons between groups. In correlation analyses, metabolic activity of the amygdala correlated with metabolic activity in the aorta (r = 0.757), bone marrow (r = 0.750), and spleen (r = 0.665), respectively. Metabolic activity in the aorta correlated with 18FDG uptake in the thoracic vertebrae (r = 0.703) and spleen (r = 0.594), respectively. Metabolic activity in the spleen also correlated with 18FDG uptake in the bone marrow (r = 0.620). Metabolic activity in the adjacent erector spinae skeletal muscle (our control tissue) was not positively correlated with any other region of interest. Finally, there were no statistically significant mean differences in metabolic activity between the three groups: nonsmokers, electronic cigarette users, and smokers in any target tissue. Amygdala metabolic activity, as measured by 18FDG uptake in FDG‐PET/CT scans, positively correlated with inflammation in the splenocardiac tissues, including: the aorta, bone marrow, and spleen, underscoring the existence of a neural‐hematopoietic‐inflammatory axis in healthy, young adults.