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Abstract Wolverine distribution contracted along the southern periphery of its range in North America during the 19th and 20th centuries due primarily to human influences. This history, along with low densities, sensitivity to climate change, and concerns about connectivity among fragmented habitats spurred the recent US federal listing of threatened status and special concern status in Canada. To help inform large scale landscape connectivity, we collected 882 genetic samples genotyped at 19 microsatellite loci. We employed multiple statistical models to assess the landscape factors (terrain complexity, human disturbance, forest configuration, and climate) associated with wolverine genetic connectivity across 2.2 million km2 of southwestern Canada and the northwestern contiguous United States. Genetic similarity (positive spatial autocorrelation) of wolverines was detected up to 555 km and a high-to-low gradient of genetic diversity occurred from north-to-south. Landscape genetics analyses confirmed that wolverine genetic connectivity has been negatively influenced by human disturbance at broad scales and positively influenced by forest cover and snow persistence at fine- and broad–scales, respectively. This information applied across large landscapes can be used to guide management actions with the goal of maintaining or restoring population connectivity.

Abstract Genetic rescue—an increase in population fitness following the introduction of new alleles—has been proven to ameliorate inbreeding depression in small, isolated populations, yet is rarely applied as a conservation tool. A lingering question regarding genetic rescue in wildlife conservation is how long beneficial effects persist in admixed populations. Using data collected over 40 years from 1192 endangered Florida panthers (Puma concolor coryi) across nine generations, we show that the experimental genetic rescue implemented in 1995—via the release of eight female pumas from Texas—alleviated morphological, genetic, and demographic correlates of inbreeding depression, subsequently preventing extirpation of the population. We present unequivocal evidence, for the first time in any terrestrial vertebrate, that genetic and phenotypic benefits of genetic rescue remain in this population after five generations of admixture, which helped increase panther abundance (> fivefold) and genetic effective population size (> 20-fold). Additionally, even with extensive admixture, microsatellite allele frequencies in the population continue to support the distinctness of Florida panthers from other North American puma populations, including Texas. Although threats including habitat loss, human-wildlife conflict, and infectious diseases are challenges to many imperiled populations, our results suggest genetic rescue can serve as an effective, multi-generational tool for conservation of small, isolated populations facing extinction from inbreeding.

Abstract Background Studies of animal habitat selection are important to identify and preserve the resources species depend on, yet often little attention is paid to how habitat needs vary depending on behavioral state. Fishers (Pekania pennanti) are known to be dependent on large, mature trees for resting and denning, but less is known about their habitat use when foraging or moving within a home range. Methods We used GPS locations collected during the energetically costly pre-denning season from 12 female fishers to determine fisher habitat selection during two critical behavioral activities: foraging (moving) or resting, with a focus on response to forest structure related to past forest management actions since this is a primary driver of fisher habitat configuration. We characterized behavior based on high-resolution GPS and collar accelerometer data and modeled fisher selection for these two behaviors within a home range (third-order selection). Additionally, we investigated whether fisher use of elements of forest structure or other important environmental characteristics changed as their availability changed, i.e., a functional response, for each behavior type. Results We found that fishers exhibited specialist selection when resting and generalist selection when moving, with resting habitat characterized by riparian drainages with dense canopy cover and moving habitat primarily influenced by the presence of mesic montane mixed conifer forest. Fishers were more tolerant of forest openings and other early succession elements when moving than resting. Conclusions Our results emphasize the importance of considering the differing habitat needs of animals based on their movement behavior when performing habitat selection analyses. We found that resting fishers are more specialist in their habitat needs, while foraging fishers are more generalist and will tolerate greater forest heterogeneity from past disturbance.

Natural resource agencies are frequently tasked with monitoring populations of at-risk species to ensure management activities do not negatively affect the viability of wildlife populations. Typically, these monitoring efforts evaluate trends in a population’s abundance, occupancy, or geographic distribution. Often, surveys provide local information, but results are generally not incorporated into broad-scale monitoring efforts that focus on range-wide population changes due to their variable nature in both spatial extent and effort. We investigated whether aggregating these local (hereafter “variable”) surveys can generate enough statistical power to estimate broad-scale population trends using simulations of declining populations of fishers (Pekania pennati) over a 10-year time horizon. Our simulations included three population sizes which we refer to as abundant, common, and rare (N0 = 700, 350, and 100 individuals, respectively) with each declining at a rapid and moderate pace (λ = 0.933, and 0.977, respectively). For each population, we simulated variable surveys using an occupancy framework to subsample the population with parameters that mimic combining multiple independent monitoring efforts which vary annually in location, and effort. Regardless of spatial consistency of annual sampling, there was minimal variation in statistical power under both high and low detection probability simulations. However, when sampling effort varied each year, statistical power was lower for most populations and sampling scenarios when compared to consistent sampling effort unless some baseline level of sampling effort was reliably achieved in all years. In many cases, adding low-level consistent baseline sampling to variable surveys resulted in statistical power close to that of consistent sampling efforts. Our results suggest statistical power is driven by annual consistency in the proportion of landscape sampled rather than spatial consistency in sampling locations. This result indicates that current variable surveys could be leveraged and combined to detect population declines for at-risk species at broad-scales if a baseline proportion of landscape is robustly sampled. The level of baseline sampling is highly dependent on population size and magnitudes of population change. In simulations with a common or abundant population experiencing a rapid decline, a baseline survey effort of at least 5% of the landscape in combination with variable surveys resulted in statistical power consistently above the standard threshold of 0.80 for occupancy monitoring. Leveraging existing local efforts to achieve high detection probability and baseline sampling would reduce financial and logistical burdens of broad-scale wildlife monitoring efforts.

Background In this open-label, randomized, non-comparative, multicenter phase II study (Alliance A091401) we report on three expansion cohorts treated with nivolumab (N) with and without ipilimumab (N+I) and provide a multi-omic correlative analysis of actionable biomarkers.Methods Patients were randomized (non-comparative) to receive either N or N+I. The primary endpoint was a 6-month confirmed response rate (CRR) defined by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included treatment-related adverse events (TRAEs), progression-free survival, and overall survival. Multi-omic correlative analyses were conducted using samples from both the primary and expansion cohorts.Results A total of 66 patients were evaluated for the primary endpoint with disease including gastrointestinal stromal tumor (GIST, n=18), undifferentiated pleomorphic sarcoma (UPS, n=24), and dedifferentiated liposarcoma (DDLPS, n=24). Neither N nor N+I achieved a complete or partial response in the GIST expansion cohort. In DDLPS and UPS, the primary response endpoint of CRR was met with N+I (both 16.6%, 2/12) but not with N alone (both 8.3%, 1/12). In the GIST cohort, TRAE was higher with N+I treatment, halting enrollment as required per protocol. In a correlative analysis of patients for the expansion cohort and the original cohort (n=86), traditional biomarkers of immunotherapy response were not correlated with response in any histological subtype. Markers of genomic instability including the presence of gene fusions and increased subclonal mutations correlated with improved clinical outcomes.Conclusions This expansion cohort reaffirms the outcomes of A091401. There remains a pressing need to determine the role of and predictive biomarkers for immunotherapy in sarcoma.Trial registration number NCT02500797.

Neuroinflammation is a miscreant in accelerating progression of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, treatments targeting neuroinflammation alone have led to disappointing results in clinical trials. Both neuronal and non-neuronal cell types have been implicated in the pathogenesis of ALS, and multiple studies have shown correction of each cell type has beneficial effects on disease outcome. Previously, we shown that AAV9-mediated superoxide dismutase 1 (SOD1) suppression in motor neurons and astrocytes significantly improves motor function and extends survival in ALS mouse models. Despite neuron and astrocyte correction, ALS mice still succumb to death with microgliosis observed in endpoint tissue. Therefore, we hypothesized that the optimal therapeutic approach will target and simultaneously correct motor neurons, astrocytes, and microglia. Here, we developed a novel approach to indirectly target microglia with galectin-1 (Gal1) and combined this with our previously established AAV9.SOD1.short hairpin RNA treatment. We show Gal1 conditioning of SOD1G93A microglia decreases inflammatory markers and rescues motor neuron death in vitro. When paired with SOD1 downregulation, we found a synergistic effect of combination treatment in vivo and show a significant extension of survival of SOD1G93A mice over SOD1 suppression alone. These results highlight the importance of targeting inflammatory microglia as a critical component in future therapeutic development.

Abstract Species' ranges are shifting rapidly with climate change, altering the composition of biological communities and interactions within and among species. Hybridization is among the species interactions that may change markedly with climate change, yet it is understudied relative to others. We used non‐invasive genetic detections to build a maximum entropy species distribution model and investigate the factors that delimit the present and future ranges of American marten (Martes americana) and Pacific marten (Martes caurina) in a contact zone in the Northern Rockies. We found that climate change will decrease the suitable habitat predicted for both species, as well as the amount of overlap in predicted suitable habitat between the species. Interestingly, predicted suitable habitat for Pacific marten extended further north in the study region than our genetic detections for the species, suggesting that biotic factors, such as interactions with American marten, may affect the realized range of this species. Our results suggest that future work investigating the interactions among biotic and abiotic factors that influence hybrid zone dynamics is important for predicting the futures of these two species in this area under climate change.

Abstract Designing complex synthetic materials for enzyme immobilization could unlock the utility of biocatalysis in extreme environments. Inspired by biology, we investigate the use of random copolymer brushes as dynamic immobilization supports that enable supra-biological catalytic performance of immobilized enzymes. This is demonstrated by immobilizing Bacillus subtilis Lipase A on brushes doped with aromatic moieties, which can interact with the lipase through multiple non-covalent interactions. Incorporation of aromatic groups leads to a 50 °C increase in the optimal temperature of lipase, as well as a 50-fold enhancement in enzyme activity. Single-molecule FRET studies reveal that these supports act as biomimetic chaperones by promoting enzyme refolding and stabilizing the enzyme’s folded and catalytically active state. This effect is diminished when aromatic residues are mutated out, suggesting the importance of π-stacking and π-cation interactions for stabilization. Our results underscore how unexplored enzyme-support interactions may enable uncharted opportunities for using enzymes in industrial biotransformations.

Physical and genetic isolation are recognized as significant threats to wildlife, especially in large carnivores inhabiting fragmented landscapes. We conducted an initial genetic assessment of pumas (Puma concolor) using 19 microsatellite loci for the emblematic puma population in the Torres del Paine UNESCO Biosphere Reserve in southernmost Chile, which exhibits some distinctive phenology that some local people speculate may be due to isolation and inbreeding depression. We extracted DNA from 385 scats collected in the field, of which 96 were identified as puma, representing 20 unique individuals. Torres del Paine pumas exhibited an Ho (0.51) only slightly lower than He (0.53), with 2 of the 19 loci significantly out of Hardy–Weinberg Equilibrium. Tests for a recent bottleneck of the population were not significant. The small sample size of individuals notwithstanding, these results seemingly do not support high levels of inbreeding. We also identified individual pumas in the field and assessed them for observable cowlicks (twirls of fur on their backs), a trait some have associated with genetic inbreeding depression in other puma populations. A total of 7 of 39 pumas exhibited cowlicks, consistent with geographic patterns of cowlicks within the species. Our tests exploring population structure among local pumas provided the most support for a single-population cluster, but we explored secondary structures as well, given its conservation implications. We encourage additional sampling in the region to further explore population structure and connectivity and determine the conservation status of the region’s pumas to guide the development of best strategies to ensure their persistence.

Abstract The need for widespread occurrence data to inform species conservation has prompted interest in large, national‐scale environmental DNA (eDNA) monitoring strategies. However, targeted eDNA assays are seldom validated for use across broad geographic areas. Here, we validated 46 new and previously published probe‐based qPCR assays targeting invasive species throughout the continental United States. We drew upon current taxonomies, range maps, publicly available sequences, and tissue archives to evaluate all potentially sympatric confamilial species and genetically similar extrafamilial taxa. Out of 5276 unique assay‐nontarget taxon combinations, we were able to test 4206 (80%). We characterized levels of validation and specificity for each of eight federal geographic regions and provided an online tool with state‐level information, as well as detailed assay descriptions in an appendix. Specificity testing benefited from extensive use of eDNAssay—a machine learning classifier trained to predict qPCR cross‐amplification—which we found to be 96% accurate in 649 unique tests that underwent paired in silico and in vitro testing. Predictions of assay specificity (the true negative rate) were 98–100% accurate, depending on the classification threshold used. This work provides both an immediate resource for invasive species surveillance and demonstrates an enhanced in silico, geographically subdivided validation framework to aid in future large‐scale validation efforts.

Abstract Environmental DNA (eDNA) sampling is a powerful tool for rapidly characterizing biodiversity patterns for specious, cryptic taxa with incomplete taxonomies. One such group that are also of high conservation concern are North American freshwater gastropods. In particular, springsnails of the genus Pyrgulopsis (Family: Hydrobiidae) are prevalent throughout the western United States where >140 species have been described. Many of the described species are narrow endemics known from a single spring or locality, and it is believed that there are likely many additional species which have yet to be described. The distribution of these species across the landscape is of interest because habitat loss and degradation, climate change, groundwater mining, and pollution have resulted in springsnail imperilment rates as high as 92%. Determining distributions with conventional sampling methods is limited by the fact that these snails are often

Abstract Unesbulin is being investigated in combination with dacarbazine (DTIC) as a potential therapeutic agent in patients with advanced leiomyosarcoma (LMS). This paper reports the pharmacokinetics (PK) of unesbulin, DTIC, and its unreactive surrogate metabolite 5‐aminoimidazole‐4‐carboxamide (AIC) in 29 patients with advanced LMS. Drug interactions between DTIC (and AIC) and unesbulin were evaluated. DTIC (1000 mg/m2) was administered to patients with LMS via 1‐h intravenous (i.v.) infusion on day 1 of every 21‐day (q21d) cycle. Unesbulin dispersible tablets were administered orally twice weekly (b.i.w.), starting on day 2 of every cycle, except for cycle 2 (C2), where unesbulin was dosed either on day 1 together with DTIC or on day 2, 1 day after DTIC administration. The PK of DTIC, AIC, and unesbulin in cycle 1 (C1) and C2 were estimated using noncompartmental analysis. DTIC and AIC were measurable immediately after the start of infusion and reached maximum plasma concentration (Cmax) immediately or shortly after end of infusion at 1.0 and 1.4 h (time to Cmax), respectively. Co‐administration of unesbulin orally at 200 mg or above with DTIC inhibited cytochrome P450 (CYP)1A2‐mediated DTIC metabolism, resulting in 66.7% reduction of AIC exposures. Such inhibition could be mitigated when unesbulin was dosed the day following DTIC infusion. Repeated unesbulin dosing demonstrated evidence of clinical CYP1A2 induction and increased AIC Cmax by 69.4% and area under concentration‐time curve to infinity by 57.9%. No meaningful difference in unesbulin PK was observed between C2 and C1. The combination therapy of 1000 mg/m2 i.v. DTIC q21d and 300 mg unesbulin b.i.w. in a staggered regimen is well‐tolerated in patients with LMS.

Overdose fatality review teams (OFRTs) are becoming more common across U.S. communities as a means of addressing the overdose epidemic and improving local overdose prevention strategies; however, empirical examinations of the work of OFRTs are lacking. The current study seeks to characterize recommendations for local overdose prevention strategies made by county-level OFRTs across Indiana in order to understand their practices., Methods: A qualitative descriptive content analysis was conducted on recommendations made by 19 county-level OFRTs across Indiana in 2022., Results: OFRTs generated 1512 recommendations during 2022 based on case reviews of 291 overdose deaths occurring across 19 Indiana counties; of those, 26.8 % (n=405) were specific to the case reviewed, rather than relevant to the broader community, and were not further coded. The remaining 1109 recommendations were coded according to their overall scope, recommendation strategy, and target agency. The most common recommendations addressed substance use more broadly (e.g., improving substance use screening/assessment in healthcare settings), followed by recommendations directly addressing overdose risk (e.g., naloxone distribution, increasing harm reduction programs). Other common recommendations related to mental health, OFRT practices, and addressing social determinants of health. Common recommendation strategies were to implement new services or service improvements., Conclusion: Results highlight the extent of further efforts needed to improve overdose prevention and the need for further research and support of OFRTs across the United States., Competing Interests: Declaration of Competing Interest Authors have no conflict of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: Sudden Unexpected Death in Epilepsy (SUDEP) is a complication of epilepsy responsible for approximately 1 death per 1000 patients. The literature has demonstrated minimal SUDEP disclosure between providers and patients, although patients have consistently reported desire to know about their risk. However, the majority of these studies has been conducted in Caucasian populations which did not seek to include lower socio-economic class individuals. Thus, the purpose of this study is to determine patient and provider attitudes regarding SUDEP disclosure at a community health center serving minority, predominantly Hispanic, patients., Methods: This cross-sectional study utilized surveys distributed to patients with epilepsy (n = 20), patients with diabetes (n = 20), those with no chronic disease (n = 20) and providers (n = 13). Online surveys were distributed to 13 providers whereas phone surveys were conducted for patients with epilepsy. In-person surveys were distributed to patients with diabetes and no chronic disease to serve as comparison groups. Surveys were available in both Spanish and English. Patient surveys consisted of demographic information and questions evaluating their current knowledge and preferences regarding disclosure of a potentially fatal disorder., Results: Twenty patients with epilepsy, 20 patients with diabetes, 20 patients without chronic diseases, and 9 providers responded to the online or in-person surveys. Of the patients with epilepsy, 90 % (n = 18/20) were Hispanic which was not significantly different from the comparison groups. 45 % (n = 9/20) believed they had a higher rate of death due to epilepsy with only 3 patients having heard of SUDEP prior to the survey, and only 1 learning this from a physician. All patients wanted to know everything there was to know regarding their condition, including a higher risk of unexpected death. Most patients (85%, n = 17/20) believe everyone with epilepsy should be informed of SUDEP and this information should come from their provider (90 %, n = 18/20). Results were similar for both comparison groups, except patients with diabetes unanimously desired to know about a theoretical risk of death at the time of diagnosis. Of the providers, 66.7% (n = 6/9) never discuss SUDEP, with the remaining 33.3% (n = 3/9) discussing SUDEP rarely. The primary reason for not discussing SUDEP was not knowing enough about it (66.7%, n = 5/9)., Conclusion: Almost all patients with epilepsy had no knowledge of SUDEP, yet desired to know this information within the first two visits. Providers in the primary care setting rarely discuss SUDEP, most often due to lack of knowledge. These results are very similar to those found in mainly white, higher socioeconomic populations and indicate that race should not be a barrier to SUDEP disclosure., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Buchhalter serves as a paid consultant to the Epilepsy Foundation, Epilepsy Study Consortium, Biocodex Inc, Epilog Clouds of Care and UCB Inc. He receives research support from the Dravet Syndrome Foundation and serves as a co-chair for Partners Against Mortality in Epilepsy on a volunteer basis. No other authors have any declarations of competing interests.]., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Prescribing medications for opioid use disorders (MOUD), including buprenorphine, naltrexone, and methadone, to adolescents remains an underused evidence-based strategy for reducing harms associated with opioid use., Objective: To identify potential associations between clinician- and community-level characteristics regarding clinicians' self-reported willingness to prescribe MOUD to adolescents., Design, Setting, and Participants: This cross-sectional study included a phone survey of Indiana clinicians and spatial analysis of community-level characteristics. Clinicians were eligible for inclusion in analyses if actively providing health care and listed on the Buprenorphine Practitioner Locator website, a publicly available national registry of clinicians possessing a waiver to legally prescribe buprenorphine (ie, waivered clinicians)., Exposures: Community-level characteristics, including total population, rurality or urbanicity, percentage with incomes below the federal poverty line, and racial or ethnic makeup., Main Outcomes and Measures: Clinicians were asked about their willingness to prescribe MOUD to adolescents younger than 18 years if clinically indicated. Responses were recorded as no, yes, or yes with conditions., Results: Among the 871 clinicians listed on the website as of July 2022, 832 were eligible for inclusion and contacted by phone. Among waivered clinicians, 759 (91.2%) reported being unwilling to prescribe MOUD to adolescents, 73 clinicians (8.8%) reported willingness to prescribe MOUD to adolescents, and only 24 (2.9%) would do so without conditions. A multivariable logistic regression model including spatially lagged community-level variables showed that, among areas with waivered clinicians, clinicians practicing in more populated areas were significantly less likely to prescribe to adolescents (β = 0.65; 95% CI, 0.49-0.87; P = .003). Similarly, those in more rural areas were significantly more likely to prescribe to adolescents (β = 1.27; 95% CI, 1.02-1.58; P = .03). Variation in clinician willingness to prescribe was not explained by other community-level characteristics. Among all waivered clinicians, advanced practice clinicians were less likely than physicians to report willingness to prescribe (β = 0.58; 95% CI, 0.35-0.97; P = .04), as were physicians without any specialty training relevant to MOUD prescribing when compared with family medicine clinicians (β = 0.40; 95% CI, 0.18-0.89; P = .03). A small subgroup of waivered clinicians had training in pediatrics (13 clinicians [1.6%]), and none were willing to prescribe MOUD to adolescents., Conclusions and Relevance: From this cross-sectional study, it appears that Indiana adolescents continued to face gaps in access to MOUD treatment, despite its well-established efficacy. Programs that support primary care practitioners, including family medicine clinicians and pediatricians, in safe and appropriate use of MOUD in adolescents may bridge these gaps.

Mastery learning with fixed end points and variable training time leads to more consistent expertise but is difficult to implement. Here we piloted mastery learning of laryngoscopy with independent practice. 35 learners participated in independent mastery learning on a manikin that provides automated performance feedback. A pre- and postpractice assessment of intubation skills was completed. After an average of 21 minutes of open practice, the percentage of subjects that met mastery criteria improved from 24% to 89% (P < .05). Independent intubation practice with manikin feedback facilitated mastery learning, enhanced procedural education, and may impact clinical care., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Introduction: The purpose of this review is to examine African Ebola outbreaks from their first discovery to the present, to determine how the medical and public health response has changed and identify the causes for those changes. We sought to describe what is now known about the epidemiology and spread of Ebola virus disease (EVD) from the significant outbreaks that have occurred and outbreak control methods applied under often challenging circumstances. Given the substantial role that the U.S. Government and the U.S. DoD have played in the 2014 to 2016 West African Ebola outbreak, the role of the DoD and the U.S. Africa Command in controlling EVD is described., Materials and Methods: A descriptive method design was used to collect and analyze all available Ebola outbreak literature using the PubMed database. An initial literature search was conducted by searching for, obtaining, and reading original source articles on all major global Ebola outbreaks. To conduct a focused search, we used initial search terms "Ebola outbreak," "Ebola virus disease," "Ebola response," "Ebola countermeasures," and also included each country's name where Ebola cases are known to have occurred. From the 4,673 unique articles obtained from this search and subsequent article title review, 307 articles were identified for potential inclusion. Following abstract and article review, 45 original source articles were used to compile the history of significant Ebola outbreaks. From this compilation, articles focused on each respective subsection of this review to delineate and describe the history of EVD and response, identifying fundamental changes, were obtained and incorporated., Results: We present known Ebola virus and disease attributes, including a general description, seasonality and location, transmission capacity, clinical symptoms, surveillance, virology, historical EVD outbreaks and response, international support for Ebola outbreak response, U.S. DoD support, medical countermeasures supporting outbreak response, remaining gaps to include policy limitations, regional instability, climate change, migration, and urbanization, public health education and infrastructure, and virus persistence and public awareness., Conclusions: The health and societal impacts of EVD on Africa has been far-reaching, with about 35,000 cases and over 15,000 deaths, with small numbers of cases spreading globally. However, the history of combatting EVD reveals that there is considerable hope for African nations to quickly and successfully respond to Ebola outbreaks, through use of endemic resources including Africa CDC and African Partner Outbreak Response Alliance and the U.S. Africa Command with greater DoD reachback. Although there remains much to be learned about the Ebola virus and EVD including whether the potential for novel strains to become deadly emerging infections, invaluable vaccines, antivirals, and public health measures are now part of the resources that can be used to combat this disease., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Mycoplasma bovis is a bacterial pathogen endemic to cattle. In the early 2000s, M. bovis emerged as a cause of respiratory disease in American bison (Bison bison), causing significant morbidity and mortality. Bison herds that experience an outbreak of M. bovis are at higher risk for subsequent outbreaks, suggesting that chronic, subclinical infections can be established. Antemortem testing is therefore crucial to disease management; however, the precise sampling method to maximize detection of M. bovis in bison is unknown. We evaluated two sample types-superficial nasal swabs and deep nasopharyngeal swabs-collected from apparently healthy or symptomatic bison from January 2021 through December 2022. We used real-time PCR to detect M. bovis in 76/938 bison (8.1%) from 11 herds. For bison testing positive on at least one swab type, M. bovis was detected in 63/76 (82.8%) deep nasopharyngeal swabs and 29/73 (38.1%) superficial nasal swabs. Agreement between swabs for positive bison was 21% (n=16, kappa coefficient 0.319). We conclude that deep nasopharyngeal swabbing is more sensitive than superficial nasal swabbing for detection of M. bovis in bison and that low agreement between methods may be related to stage of infection. We further tested pooled samples by PCR and found that pooling of up to five samples can be effective to increase throughput and minimize costs. Management of wild bison relies on the ability to relocate animals to maintain gene flow and healthy populations. Sensitive and specific diagnostic tests are needed to inform decisions and minimize risk of transmission, especially from subclinical carriers. This study provides valuable insight that will inform best practices for M. bovis testing, thereby supporting the conservation of bison as healthy wildlife, which in turn promotes ecological restoration, safeguards cultural practices of Tribal Nations, and upholds the bison as a unique American icon., (© Wildlife Disease Association 2024.)

Background: Research demonstrates gaps in medications for opioid use disorder uptake (MOUDs; methadone, buprenorphine, and naltrexone) especially among adolescents. These gaps may be partly attributable to attitudes about and training in MOUDs among youth-serving professionals. We extended prior research by conducting descriptive analyses of attitudes regarding effectiveness and acceptability of MOUDs, as well as training in MOUDs, among youth legal system (YLS) employees and community mental health center (CMHC) personnel who interface professionally with youth., Methods: Using survey data from participants (n = 181) recruited from eight Midwest counties, we examined: (1) differences in MOUD attitudes/training by MOUD type and (2) by respondent demographics, and (3) prediction of MOUD attitudes/training by participant-reported initiatives to implement evidence-based practices (EBPs), workplace culture around EBPs, and workplace stress. Attitudes and training were measured in reference to five MOUD types (methadone, oral buprenorphine, injectable buprenorphine, oral naltrexone, injectable naltrexone) on three subscales (effectiveness, acceptability, training)., Results: Wilcoxon signed-rank tests demonstrated that most outcomes differed significantly by MOUD type (differences observed among 22 of 30 tests). Kruskal-Wallis tests suggested MOUD differences based on demographics. For methadone, CMHC providers endorsed greater perceived effectiveness than YLS providers and age explained significant differences in perceived effectiveness. For buprenorphine, CHMC providers viewed oral or injectable buprenorphine as more effective than YLS employees, respondents from more rural counties viewed oral buprenorphine as more effective than those from less rural counties, and age explained differences in perceived effectiveness. For naltrexone, perceived gender differed by gender. Hierarchical ordinal logistic regression analysis did not find an association between personal initiatives to implement EBPs, workplace culture supporting EBPs, or workplace stress and effectiveness or acceptability of MOUDs. However, personal initiatives to implement EBPs was associated with training in each MOUD., Conclusions: These results highlight a few key findings: effectiveness/acceptability of and training in MOUDs largely differ by MOUD type; setting, rurality, age, gender, and education explain group differences in perceived effectiveness of and training in MOUDs; and implementing EBPs is associated with training in MOUDs. Future research would benefit from examining what predicts change in MOUD attitudes longitudinally., (© 2024. The Author(s).)

Background: Overdose Fatality Review (OFR) is an important public health tool for shaping overdose prevention strategies in communities. However, OFR teams review only a few cases at a time, which typically represent a small fraction of the total fatalities in their jurisdiction. Such limited review could result in a partial understanding of local overdose patterns, leading to policy recommendations that do not fully address the broader community needs., Objective: This study explored the potential to enhance conventional OFRs with a data dashboard, incorporating visualizations of touchpoints-events that precede overdoses-to highlight prevention opportunities., Methods: We conducted 2 focus groups and a survey of OFR experts to characterize their information needs and design a real-time dashboard that tracks and measures decedents' past interactions with services in Indiana. Experts (N=27) were engaged, yielding insights on essential data features to incorporate and providing feedback to guide the development of visualizations., Results: The findings highlighted the importance of showing decedents' interactions with health services (emergency medical services) and the justice system (incarcerations). Emphasis was also placed on maintaining decedent anonymity, particularly in small communities, and the need for training OFR members in data interpretation. The developed dashboard summarizes key touchpoint metrics, including prevalence, interaction frequency, and time intervals between touchpoints and overdoses, with data viewable at the county and state levels. In an initial evaluation, the dashboard was well received for its comprehensive data coverage and its potential for enhancing OFR recommendations and case selection., Conclusions: The Indiana touchpoints dashboard is the first to display real-time visualizations that link administrative and overdose mortality data across the state. This resource equips local health officials and OFRs with timely, quantitative, and spatiotemporal insights into overdose risk factors in their communities, facilitating data-driven interventions and policy changes. However, fully integrating the dashboard into OFR practices will likely require training teams in data interpretation and decision-making., (©Amey Salvi, Logan A Gillenwater, Brandon P Cockrum, Sarah E Wiehe, Kaitlyn Christian, John Cayton, Timothy Bailey, Katherine Schwartz, Allyson L Dir, Bradley Ray, Matthew C Aalsma, Khairi Reda. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 11.06.2024.)

Background: Osteosarcoma is the most common primary bone malignancy. It has classically been described as having a bimodal incidence by age. We sought to identify whether the bimodal incidence distribution still exists for osteosarcoma using the SEER and NIS databases., Methods: Incidence rates of primary osteosarcoma between 2000-2021 were analyzed by age at diagnosis, year of occurrence, sex, and tumor site from the SEER Research Data, 17 Registries, Nov 2023 Sub (2000-2021). The incidence of cases in 35-64 year-olds and 65 and above was compared statistically to determine if there is an increased incidence in the later ages. Incidence of tumors of the long bones of the lower limbs from the NIS discharge database 2012-2019 was also analyzed for comparison., Results: Overall, 5,129 cases of osteosarcoma were reported in the SEER database. Across the 22 calendar year span, a consistent first peak appeared in the second decade of life. There was no consistent second peak in the 35+ age group. There were 86,100 discharges with long bone tumors analyzed in the NIS data which exhibited nearly identical patterns., Conclusions: Our analysis shows that the incidence of osteosarcoma is no longer bimodally distributed but rather unimodally distributed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier GmbH.)

Introduction: Rates of substance use are high among youth involved in the legal system (YILS); however, YILS are less likely to initiate and complete substance use treatment compared to their non legally-involved peers. There are multiple steps involved in connecting youth to needed services, from screening and referral within the juvenile legal system to treatment initiation and completion within the behavioral health system. Understanding potential gaps in the care continuum requires data and decision-making from these two systems. The current study reports on the development of data dashboards that integrate these systems' data to help guide decisions to improve substance use screening and treatment for YILS, focusing on end-user feedback regarding dashboard utility., Methods: Three focus groups were conducted with n = 21 end-users from juvenile legal systems and community mental health centers in front-line positions and in decision-making roles across 8 counties to gather feedback on an early version of the data dashboards; dashboards were then modified based on feedback., Results: Qualitative analysis revealed topics related to (1) important aesthetic features of the dashboard, (2) user features such as filtering options and benchmarking to compare local data with other counties, and (3) the centrality of consistent terminology for data dashboard elements. Results also revealed the use of dashboards to facilitate collaboration between legal and behavioral health systems., Conclusions: Feedback from end-users highlight important design elements and dashboard utility as well as the challenges of working with cross-system and cross-jurisdiction data., (© 2024. The Author(s).)

Background: As oral PrEP scales up in Nigeria, information about uptake, use pattern and client preference in a real-world, implementation setting is invaluable to guide refining service provision and incorporation of oral PrEP and other prevention measures into routine health services. To add to this body of knowledge, our study examines factors associated with discontinuation of PrEP among HIV negative individuals across two large scale programs in Nigeria., Methods: Using program implementation data from two large-scale HIV projects in Akwa Ibom and Cross River states in Nigeria between January 2020 and July 2021, we used logistic regression to explore factors associated with early discontinuation (i.e., stopping PrEP within one month of starting) among HIV-negative individuals who initiated PrEP in the programs., Results: Of a total of 26,325 clients; 22,034 (84%) discontinued PrEP within the first month. The odds of PrEP discontinuation were higher among clients who enrolled in community-based distribution sites (aOR 2.72; 95% C.I: 2.50-2.96) compared to those who enrolled in program-supported facilities and never married (aOR 1.76; 95% C.I: 1.61-1.92) compared to married clients. Clients who initiated PrEP because of high-risk sexual behaviour (aOR 1.15, 95% C.I 1.03-1.30) or inconsistent use or non-use of condoms (aOR 1.96, 95% C.I 1.60-2.41) had greater odds of discontinuing PrEPthan those who initiated PrEP because they were in a serodifferent relationship., Conclusion: The behavioural and demographic factors associated with early discontinuation of PrEP suggest that risk stratification of pre-initiation and follow up counselling may be helpful in raising continuation rates. On the service delivery side, strategies to strengthen follow-up services provided by community-based distribution sites need to be introduced. Overall, the low continuation rate calls for a review of programmatic approaches in provision of PrEP services in Nigeria., (© 2024. The Author(s).)

Background: Overuse of antimicrobials in residents of long-term care homes is common and can result in harm. Antimicrobial stewardship interventions are needed in the long-term care (LTC) homes setting to improve the appropriate use of antimicrobials. Previous literature has highlighted the importance of documenting antimicrobial indication as a strategy that contributes to improve antimicrobial use; however, there is a lack of evidence in LTC homes. This study examines the prevalence, clarity, and facility-level variability of antibiotic indication documentation in this setting., Methods: This is an observational retrospective study of oral antibiotic prescriptions dispensed to 218 homes between January 1, 2021 and December 31, 2022 in Ontario, Canada. Indication was obtained from reviewing antibiotic prescription data. Clarity was determined by comparing documented indication to the National Antimicrobial Prescribing Survey (NAPS). Descriptive analysis was performed to examine the prevalence and clarity of indication documentation. Funnel plots were generated to examine variability in prevalence of indication documentation and clarity at the home level., Results: Overall, 22.9% (7998/34,867) of prescriptions had an indication documented. The proportion of indications that were clear was 37% (2984/7998). The most common indications were for urinary (45%), skin and soft tissue (19.9%) and respiratory infections (15.0%). At the home level, the median prevalence of indication was 19.6% (interquartile range [IQR]: 10.8%-31.4%) and median prevalence of clear indications was 35.1% (IQR: 23.8%-42.9%). Funnel plots revealed substantial variability in indication prevalence with 46.3% of homes falling outside of 99% limits but minimal variability in indication clarity between homes with only 8.7% of homes outside of 99% control limits., Conclusions: There is an opportunity to increase both the prevalence and clarity of antibiotic prescriptions in LTC homes. Future work should focus on determining how best to support prescription indication documentation in this setting with consideration being given to prescription workflow and most common antibiotic prescription indications., (© 2024 His Majesty the King in Right of Canada. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society. Reproduced with the permission of the Minister of Ontario Agency for Health Protection and Promotion (Public Health Ontario).)

Importance: Occupational therapy practitioners use standardized assessments to guide their clinical decision-making, but it is unclear how well performance on standardized assessments translates to performance at home., Objective: To understand the concurrent and predictive validity of patient-reported outcomes and performance-based assessments for monitoring performance at home within the context of medication management and adherence., Design: Exploratory study., Setting: Participants completed standardized assessments in a lab or at home, which were followed by home-based electronic monitoring of medication adherence., Participants: Sixty community-dwelling adults with hypertension or stroke who independently took antihypertensive medications., Outcomes and Measures: Participants completed the Hill-Bone Medication Adherence Scale, the Hill-Bone Medication Adherence Reasons Scale, the Performance Assessment of Self-Care Skills Medication Management subtask, and the Executive Function Performance Test-Enhanced Medication Management subtest. Then, they used an electronic pill cap to monitor medication adherence at home for 1 month., Results: Patient-reported outcomes and performance-based assessments in the context of medication management and adherence demonstrated poor concurrent and predictive validity to medication adherence at home., Conclusions and Relevance: There is a gap between what people think they will do, what they can do on a standardized assessment, and what they actually do at home. Future research is needed to strengthen concurrent and predictive validity to clinically meaningful outcomes. Plain-Language Summary: Occupational therapy practitioners should use caution when using standardized assessments to try to predict client performance at home. They should also continue to use a battery of assessments, clinical reasoning, and client preferences to guide their decision-making for monitoring performance at home within the context of medication management and adherence., (Copyright © 2024 by the American Occupational Therapy Association, Inc.)

Providing anesthesia and analgesia for mouse subjects is a common and critical practice in the laboratory setting. This practice is necessary for performing invasive procedures, achieving prolonged immobility for sensitive imaging modalities (magnetic resonance imaging, for instance), and providing intra- and post-procedural pain relief. In addition to facilitating the procedures performed by the investigator, the provision of anesthesia and analgesia is crucial for the preservation of animal welfare and for humane treatment of animals used in research. Furthermore, anesthesia and analgesia are important components of animal use protocols reviewed by Institutional Animal Care and Use Committees, requiring careful consideration and planning for the particular animal model. In this article, we provide technical guidance for the investigator, covering the provision of anesthesia by two routes (injectable and inhalant), guidelines for monitoring anesthesia, current techniques for recognition of pain, considerations for administering preventative analgesia, and considerations for post-operative care. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Injectable anesthesia Basic Protocol 2: Inhalant anesthesia Basic Protocol 3: Assessing pain., (© 2024 Wiley Periodicals LLC.)

Sensory processing is a fundamental aspect of the nervous system that plays a pivotal role in the cognitive decline observed in older individuals with dementia. The "sensory diet", derived from sensory integration theory, may provide a tailored approach to modulating sensory experiences and triggering neuroplastic changes in the brain in individuals with dementia. Therefore, this review aimed to investigate the current knowledge regarding the sensory diet and its potential application to dementia. This review encompassed an extensive search across multiple databases, including PubMed, Google Scholar, covering articles published from 2010 to 2023. Keywords such as "sensory integration", "sensory modulation", "healthy aging", and "dementia" were utilized to identify relevant studies. The types of materials retrieved included peer-reviewed articles, systematic reviews, and meta-analyses, ensuring a comprehensive overview of the current research landscape. This article offers a comprehensive exploration of the effectiveness of sensory diets such as tactile stimulation, auditory therapies, and visual interventions, which have demonstrated noteworthy efficacy in addressing challenges linked to aging and dementia. Research findings consistently report positive outcomes, such as improved cognitive function, elevated emotional well-being, and enhanced overall quality of life in older individuals. Furthermore, we found that the integration of sensory diets with the metaverse, augmented reality, and virtual reality opens up personalized experiences, fostering cognitive stimulation and emotional well-being for individuals during aging. Therefore, we conclude that customized sensory diets, based on interdisciplinary cooperation and leveraging technological advancements, are effective in optimizing sensory processing and improve the overall well-being of older individuals contending with sensory modulation challenges and dementia.

Introduction: Studies showed that professional dance is often associated with a high degree of acute musculoskeletal injuries. These injuries' etiology predominantly describes their biomechanical or other extrinsic factors, but there is a limited number of scientific reports dealing with the perceived stress or mental health status concerning the physical complaints especially, among Hungarian professional dancers. Materials and Methods: In this study, we used validated questionnaires (RESTQ, SEFIP, Mental Health Test) filled out by Hungarian professional female dancers (N = 168) via an online platform anonymously and analyzed statistically. Results: Our findings showed a significantly positive relationship between musculoskeletal complaints and perceived stress, an elevated level of general stress, and a higher level of resilience in this population compared to the general population. Conclusion: Dancers demonstrate a heightened perception of stress; however, they exhibit elevated scores on resilience assessments, indicative of heightened functionality in their daily lives. Stress, per se, may not be directly regarded as a causative factor for acute musculoskeletal conditions, but it could potentially influence the severity of pain sensations and subjective pain levels in the context of existing injuries. Additional investigations are warranted to elucidate the precise mechanisms by which stress exacerbates the pain experience among dancers., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rates of youth behavioral health concerns have been steadily rising. Administrative data can be used to study behavioral health service utilization among youth, but current methods that rely on identifying an associated behavioral health diagnosis or provider specialty are limited. We reviewed all procedure codes billed to Medicaid for youth in one U.S. county over a 10-year period. We identified 158 outpatient behavioral health procedure codes and classified them according to service type. This classification system can be used by health services researchers to better characterize youth behavioral health service utilization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Rodríguez, Pederson, Garcia, Schwartz, Brown and Aalsma.)

Background: Atipamezole, an α-2 adrenergic receptor antagonist, reverses the α-2 agonist anesthetic effects. There is a dearth of information on the physiological effects of these drugs in cynomolgus macaques (Macaca fascicularis). We assessed atipamezole's physiologic effects. We hypothesized atipamezole administration would alter anesthetic parameters., Methods: Five cynomolgus macaques were sedated with ketamine/dexmedetomidine intramuscularly, followed 45 min later with atipamezole (0.5 mg/kg). Anesthetic parameters (heart rate, blood pressure [systolic (SAP), diastolic (DAP), and mean (MAP) blood pressure], body temperature, respiratory rate, and %SpO2) were monitored prior to and every 10 min (through 60 min) post atipamezole injection., Results: While heart rate was significantly increased for 60 min; SAP, DAP, MAP, and temperature were significantly decreased at 10 min., Conclusions: This study indicates subcutaneous atipamezole results in increased heart rate and transient blood pressure decrease. These findings are clinically important to ensure anesthetist awareness to properly support and treat patients as needed., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Splenic rupture in a neonate is a rare but potentially fatal condition that may trigger evaluation for child abuse. It is a diagnosis of exclusion that has been reported in the surgical literature but may be underrecognized by pediatric radiologists. We report a case of a newborn with an unremarkable prenatal, delivery, and nursery course who presented with anemia, abdominal distension, and lethargy. Abdominal ultrasound with Doppler and computed tomography (CT) of the head, cervical spine, chest, abdomen, and pelvis without contrast showed findings of splenic rupture and anoxic brain injury. An extensive workup for traumatic, infectious, coagulopathic, and congenital etiologies was unrevealing, leading to a presumptive diagnosis of spontaneous splenic rupture in a neonate., (© 2024. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Purpose: The role of alcohol in young-onset breast cancer (YOBC) is unclear. We examined associations between lifetime alcohol consumption and YOBC in the Young Women's Health History Study, a population-based case-control study of breast cancer among Non-Hispanic Black and White women < 50 years of age., Methods: Breast cancer cases (n = 1,812) were diagnosed in the Metropolitan Detroit and Los Angeles County SEER registry areas, 2010-2015. Controls (n = 1,381) were identified through area-based sampling and were frequency-matched to cases by age, site, and race. Alcohol consumption and covariates were collected from in-person interviews. Weighted multivariable logistic regression was conducted to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for associations between alcohol consumption and YOBC overall and by subtype (Luminal A, Luminal B, HER2, or triple negative)., Results: Lifetime alcohol consumption was not associated with YOBC overall or with subtypes (all p trend  ≥ 0.13). Similarly, alcohol consumption in adolescence, young and middle adulthood was not associated with YOBC (all p trend  ≥ 0.09). An inverse association with triple-negative YOBC, however, was observed for younger age at alcohol use initiation (< 18 years vs. no consumption), aOR (95% CI) = 0.62 (0.42, 0.93). No evidence of statistical interaction by race or household poverty was observed., Conclusions: Our findings suggest alcohol consumption has a different association with YOBC than postmenopausal breast cancer-lifetime consumption was not linked to increased risk and younger age at alcohol use initiation was associated with a decreased risk of triple-negative YOBC. Future studies on alcohol consumption in YOBC subtypes are warranted., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Homelessness is a pervasive issue in the United States that presents significant challenges to public health. Homeless young adults (HYAs) are at particular risk for increased incidence and severity of depression. Using primary survey data ( n = 205) collected in the Phoenix Metropolitan Area, Arizona, from June to August 2022, this study aims to examine the relationship between adverse childhood experiences (ACEs) and depression among HYAs. We adopted the ACEs 10-item scale to measure childhood traumatic experiences, whereas depression was measured by using a PHQ-4 depression scale and diagnosed depression. Regression models were conducted to test the relationships between ACEs and depression outcomes while controlling for the covariates at the individual, interpersonal, and socioeconomic/living environment levels. The average PHQ-4 score was 5.01 (SD = 3.59), and 59.69% of HYAs reported being diagnosed previously with depression. The mean ACEs score was 5.22 out of 10. Other things being equal, for every one unit increase in ACEs scores, the odds of being diagnosed with depression increased by 11.5%, yet it was not statistically significant, while the PHQ-4 score increased by 0.445 ( p < 0.001). Overall, HYAs were disproportionately affected by depression. This study elucidates the complex relationship between ACEs and depression among HYAs.

Background: Families of youth involved in the juvenile justice system (YJJ) are integral to YJJ well-being, so it is important to consider the direct input of YJJ families as well as YJJ themselves in justice system reform efforts aiming to improve YJJ health outcomes., Objective: Our university research team partnered with one Midwest county's juvenile court, as well as YJJ family members, to form an advisory council to the juvenile court. We report lessons learned through a case study of this council., Methods: Researchers reviewed and analyzed council records, meeting minutes, and interviews of varied stakeholders, including system representatives, leaders of similar advisory councils, and individuals with lived experience of the juvenile justice system., Lessons Learned: Council sustainability required addressing participation barriers, valuing authentic experiences, seeking out system-based champions, and identifying concrete opportunities for members to be heard., Conclusions: Investments in community health partnerships with YJJ families could improve system efforts to meet YJJ needs.

Background: It is unclear how COVID-19 pandemic affected care and outcomes among patients who are diagnosed with ST-elevation myocardial infarction (STEMI) in the USA., Methods: We analyzed the data from National Inpatient Sample from 2016 to 2020 and assessed the impact of COVID-19 infection and the COVID-19 pandemic (year 2020) on in-hospital mortality, length of stay (LOS) and hospitalization costs.P., Results: There were 1 050 905 hospitalizations with STEMI, and there was an 8.2% reduction in admissions in 2020. Patients with COVID-19 versus those without had significantly greater in-hospital mortality (45.2% vs. 10.7%; P < 0.001). In 2020, 3.0% of hospitalizations had a diagnosis of COVID-19, and the mortality was 11.5% compared to 10.7% for patients admitted in 2016-2019 period. There was a significantly increased mortality (OR 6.25, 95% CI 5.42-7.21, P < 0.001), LOS (coefficient 3.47, 95% CI 3.10-3.84, P < 0.001) and cost (coefficient 10.69, 95% CI 8.4-12.55, P < 0.001) with COVID-19 infection compared with no infection. There was a borderline difference in mortality (OR 1.04, 95% CI 1.00- 1.09, P = 0.050) but LOS (coefficient -0.21, 95% CI-0.28 to -0.14, P < 0.001) and costs (3.14, 95% CI 2.79 to 3.49, P < 0.001) were reduced in 2020 compared to 2016-2019 period., Conclusions: In conclusion, in patients hospitalized with STEMI, COVID-19 infection was associated with increased mortality, LOS, and cost but during the pandemic year of 2020 there was a small trend for increased mortality for patients with a diagnosis of STEMI., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)