Search

Abstract Oculomotor behaviour changes in patients with Parkinson’s disease (PD) are a promising source of prodromal disease markers. Capitalizing on this phenomenon to facilitate early diagnosis requires oculomotor assessment in prodromal cohorts. We examined oculomotor behaviour in non-manifesting LRRK2 G2019S mutation carriers (LRRK2-NM), who have heightened PD risk. Seventeen LRRK2-NM participants, 47 patients with idiopathic PD, and 63 healthy age-matched control participants completed an interleaved pro- and antisaccade task while undergoing video-based eye-tracking. We analyzed between-group differences in saccade, pupil, blink, and fixation acquisition behaviour. Patients with PD showed previously demonstrated abnormalities (saccade hypometria, antisaccade errors). Relative to controls, LRRK2-NM participants and patients with PD both displayed increased short-latency prosaccades and reduced pupil velocity, plus altered fixation acquisition—less preemptive returning of gaze to the future fixation point location. Interestingly, the effect on blink probability was opposite—higher than controls in LRRK2-NM participants but lower in patients with PD. Future longitudinal studies must confirm the viability of these features as prodromal PD markers.

Abstract For over a century African swine fever (ASF) has been causing outbreaks leading to devastating losses for the swine industry. The current pandemic of ASF has shown no signs of stopping and continues to spread causing outbreaks in additional countries. Currently control relies mostly on culling infected farms, and strict biosecurity procedures. Recently a vaccine, ASFV-G-ΔI177L was approved for use in Vietnam. In this study we evaluate the long-term stability of lyophilized ASFV-G-ΔI177L. Understanding the stability of different formulations of vaccines is information necessary for deployment of vaccines to ASF outbreak areas, particularly those that do not have a reliable well established cold chain to ensure conservation of vaccine quality. In this report, we determined that ASFV-G-ΔI177L, when lyophilized under specific conditions, is stable for up to one year at 4 °C, with similar vaccine titers after storage. Next-generation sequencing analysis also determined that lyophilization and long-term storage under these conditions had no effect on the genome of ASFV as the genome remained genetically identical to the original non-lyophilized form.

Abstract This position statement addresses the critical concerns and recommended practices surrounding the use of panel food testing for diagnosing food allergies. Food allergies are a significant public health concern, and the misdiagnosis of food allergies remains a prevalent concern, made worse by the ongoing use of panel food testing. The practice of screening patients for multiple food allergens, regardless of clinical relevance, is commonly referred to as “panel food testing.” Fundamentally, a panel food test is not simply a single test; a panel food test is a series of several distinct tests for multiple foods, each with its own variable predictive value. These tests have not been adequately validated as screening tests and carry a considerable false positive rate. The resulting false diagnoses lead to unnecessary dietary restrictions, increased healthcare costs, and significant psychosocial distress for patients and their families.

Abstract Background The gut microbiota (GM) has proven to be essential for both physical health and mental wellbeing, yet the forces that ultimately shape its composition remain opaque. One critical force known to affect the GM is the social environment. Prior work in humans and free-ranging non-human primates has shown that cohabitation and frequent social interaction can lead to changes in GM composition. However, it is difficult to assess the direction of causation in these studies, and interpretations are complicated by the influence of uncontrolled but correlated factors, such as shared diet. Results We performed a 15-month longitudinal investigation wherein we disentangled the impacts of diet and social living conditions on GM composition in a captive cohort of 13 male cynomolgus macaques. The animals were in single housing for the first 3 months of the study initially with a variable diet. After baseline data collection they were placed on a controlled diet for the remainder of the study. Following this diet shift the animals were moved to paired housing for 6 months, enabling enhanced social interaction, and then subsequently returned to single housing at the end of our study. This structured sequencing of diet and housing changes allowed us to assess their distinct impacts on GM composition. We found that the early dietary adjustments led to GM changes in both alpha and beta diversity, whereas changes in social living conditions only altered beta diversity. With respect to the latter, we found that two particular bacterial families — Lactobacillaceae and Clostridiaceae — demonstrated significant shifts in abundance during the transition from single housing to paired housing, which was distinct from the shifts we observed based on a change in diet. Conversely, we found that other bacteria previously associated with sociality were not altered based on changes in social living conditions but rather only by changes in diet. Conclusions Together, these findings decouple the influences that diet and social living have on GM composition and reconcile previous observations in the human and animal literatures. Moreover, the results indicate biological alterations of the gut that may, in part, mediate the relationship between sociality and wellbeing.

Abstract Background To promote rural practice and increase enrollment in the entry-level Master of Science Physical Therapy program at the University of Alberta, the Department of Physical Therapy developed a rural physical therapy satellite campus located in a farming region in central Alberta. A distributed learning format was used to connect the rural cohort to the main urban campus. Real time video conferencing was used to connect the two campuses for all lectures, seminars and clinical skills classes. This evaluation aimed to describe a unique rural training program for physical therapy students and its effectiveness in promoting work in rural communities after graduation. Methods Physical Therapy students in the first three years (2012–2015) of commencing the rural satellite program (n = 280) were surveyed, and six focus groups were held to capture student experiences, satisfaction and engagement. Data were collected on employment locations of the 2012–2019 graduates’ first physical therapy position and current employment. Results Survey results suggested comparable levels of satisfaction and engagement for all physical therapy students regardless of campus. Focus group data revealed that students quickly accepted the distributed learning technological interface, enjoyed their local campuses, and felt connected to instructors and student colleagues. Compared to the overall physical therapy workforce, a higher percentage of physical therapists graduating from the rural campus reported working in rural centers for both their first and current jobs. Conclusion Regardless of campus, students were satisfied and equally engaged in the physical therapy program. Students who completed the physical therapy program in a rural setting tended to work rurally after graduation. A distributed learning model may be useful for other healthcare training programs to promote engagement in rural health.

Abstract Background Oral immunotherapy (OIT) is an increasingly utilized management strategy for IgE-mediated food allergy. Despite promising efficacy and effectiveness, there is still a lack of data surrounding the reasons for discontinuation of OIT. The primary reason stated in the literature for discontinuation is adverse gastrointestinal effects. Social factors contributing to OIT discontinuation have not been well reported. We hypothesize that social considerations are significant contributors to treatment discontinuation. Methods We completed a retrospective chart review of 50 patients treated in community pediatric allergy practices who discontinued OIT out of 507 patients who were started on OIT between October 1, 2017-October 27, 2022. Reasons for discontinuation were identified and classified into five main categories: unsafe care decisions, anxiety, adverse effects of OIT, uncontrolled comorbidity and social factors. Categories were not exclusive. Results 507 patients were started on OIT, with data available for 50 patients who discontinued OIT, aged 10 months to 18 years and 2 months. The overall discontinuation rate was 9.8%, of which 40 patients (80%) discontinued during buildup, 9 patients (18%) discontinued during maintenance and one patient on two food OIT discontinued one food during buildup and one during maintenance (2%). Thirty-four patients (68%) had multiple reasons for discontinuing OIT. Social factors were the most common reason for discontinuation and were identified in 32 patients (64%). Twenty-four patients (48%) discontinued OIT due to adverse effects. Gastrointestinal symptoms were the most prevalent, while anaphylaxis contributed to discontinuation in 15 patients (30%). Anxiety led to discontinuation in 17 patients (34%). Conclusions Our data highlights the importance of social factors and anxiety in the success of OIT completion. Our results support the need to consider not only the patient’s medical history, but also their social history and support networks when selecting patients who are good candidates for OIT to optimize the successful completion of OIT.

Abstract Provision of non-invasive vascular imaging results to individuals has been shown to improve cardiovascular disease risk factor control: its impact on diet remains uncertain. In this two-arm, single-blind, parallel, 12-week randomized controlled trial, 240 participants, 57.5% females aged 60–80 y had abdominal aortic calcification and clinical assessments performed at a hospital clinic. Participants were randomized 1:1 to receive (intervention n = 121) or not (control n = 119) their calcification results. Both groups received educational resources on cardiovascular disease risk control and were unblinded to the intervention. Outcome measures were performed at baseline and 12 weeks. The primary outcomes of the study were changes in fruit and vegetable intake measures over 12 weeks assessed using plasma carotenoid concentrations (biomarkers of FV intake) and a food frequency questionnaire. Secondary outcomes included 12-week changes in other aspects of the diet, physical activity, body weight, blood pressure, heart rate, lipid profile, glucose concentrations, estimated cardiovascular disease risk score, and medication use. Between-group differences were tested using linear mixed-effects regression. There were no between-group differences in the primary outcomes at 12 weeks: plasma carotenoids (mean difference +0.03 µg/mL [95%CI −0.06, 0.13]) and fruit and vegetable intakes (+18 g/d [−37, 72]). However, the provision of calcification results led to between-group differences in serum total (−0.22 mmol/L [−0.41, −0.04]) and non-HDL (−0.19 mmol/L [−0.35, −0.03]) cholesterol, and estimated cardiovascular disease risk score (−0.24% [−0.47, −0.02]). No between-group differences were seen for other secondary outcomes. In this work, providing vascular imaging results did not improve diet but did improve some cardiovascular disease risk factors (Australian and New Zealand Clinical Trials Registry ACTRN12618001087246).

Abstract Multinucleated skeletal muscle cells need to acquire additional nuclei through fusion with activated skeletal muscle stem cells when responding to both developmental and adaptive growth stimuli. A fundamental question in skeletal muscle biology has been the reason underlying this need for new nuclei in cells that already harbor hundreds of nuclei. Here we utilize nuclear RNA-sequencing approaches and develop a lineage tracing strategy capable of defining the transcriptional state of recently fused nuclei and distinguishing this state from that of pre-existing nuclei. Our findings reveal the presence of conserved markers of newly fused nuclei both during development and after a hypertrophic stimulus in the adult. However, newly fused nuclei also exhibit divergent gene expression that is determined by the myogenic environment to which they fuse. Moreover, accrual of new nuclei through fusion is required for nuclei already resident in adult myofibers to mount a normal transcriptional response to a load-inducing stimulus. We propose a model of mutual regulation in the control of skeletal muscle development and adaptations, where newly fused and pre-existing myonuclear populations influence each other to maintain optimal functional growth.

Abstract Objective This study measured eye movements in children with a history of opsoclonus‐myoclonus ataxia syndrome in order to identify abnormalities in saccade and pupil behavior that map onto specific alterations in brainstem pathways. Methods We used video‐based eye tracking while participants freely viewed 10 min of short (2–4 s) video clips without instructions. Clip transitions represented a large visual perturbation and we quantified multiple characteristics of saccade and pupil responses following these transitions in 13 children recovering from opsoclonus‐myoclonus and 13 healthy, age‐matched control participants. Results The frequency of saccades and distribution of fixation durations differed between the groups. Following the clip transitions, children recovering from opsoclonus‐myoclonus ataxia syndrome exhibited longer time to initiate saccades, leading to a delay in harvesting visual information. Clip transitions to lighter clips produced similar pupil constriction responses in the two groups. However, clip transitions to darker clips produced dilation responses that were initiated earlier and of greater magnitude in opsoclonus‐myoclonus ataxia syndrome, suggesting removal or suppression of a signal that delays dilation. Interpretation Children with a history of opsoclonus‐myoclonus ataxia syndrome demonstrated key abnormalities in saccade and pupil metrics. We propose a novel hypothesis in which dysfunction in the pathway from the superior colliculus to the mesencephalic and pontine reticular formation that houses the saccade and pupil premotor circuits could produce these results.

Abstract Background The oculomotor circuit spans many cortical and subcortical areas that have been implicated in psychiatric disease. This, combined with previous findings, suggests that eye tracking may be a useful method to investigate eating disorders. Therefore, this study aimed to assess oculomotor behaviors in youth with and without an eating disorder. Methods Female youth with and without an eating disorder completed a structured task involving randomly interleaved pro-saccade (toward at a stimulus) and anti-saccade (away from stimulus) trials with video-based eye tracking. Differences in saccades (rapid eye movements between two points), eye blinks and pupil were examined. Results Youth with an eating disorder (n = 65, M age = 17.16 ± 3.5 years) were compared to healthy controls (HC; n = 65, M age = 17.88 ± 4.3 years). The eating disorder group was composed of individuals with anorexia nervosa (n = 49), bulimia nervosa (n = 7) and other specified feeding or eating disorder (n = 9). The eating disorder group was further divided into two subgroups: individuals with a restrictive spectrum eating disorder (ED-R; n = 43) or a bulimic spectrum eating disorder (ED-BP; n = 22). In pro-saccade trials, the eating disorder group made significantly more fixation breaks than HCs (F(1,128) = 5.33, p = 0.023). The ED-BP group made the most anticipatory pro-saccades, followed by ED-R, then HCs (F(2,127) = 3.38, p = 0.037). Groups did not differ on rate of correct express or regular latency pro-saccades. In anti-saccade trials, groups only significantly differed on percentage of direction errors corrected (F(2, 127) = 4.554, p = 0.012). The eating disorder group had a significantly smaller baseline pupil size (F(2,127) = 3.60, p = 0.030) and slower pro-saccade dilation velocity (F(2,127) = 3.30, p = 0.040) compared to HCs. The ED-R group had the lowest blink probability during the intertrial interval (ITI), followed by ED-BP, with HCs having the highest ITI blink probability (F(2,125) = 3.63, p = 0.029). Conclusions These results suggest that youth with an eating disorder may have different oculomotor behaviors during a structured eye tracking task. The oculomotor behavioral differences observed in this study presents an important step towards identifying neurobiological and cognitive contributions towards eating disorders.

Abstract A novel model called PyIRI was recently developed. It constructs the ionospheric electron density for the entire day and on the entire global grid in one computation, which has a very low computational overhead. PyIRI introduced a novel approach to the computation of the global and diurnal functions and their matrix multiplication with Consultative Committee on International Radio (CCIR) coefficients or the International Union of Radio Science (URSI) coefficients, that enabled this global approach for the density specification. Since the International Reference Ionosphere‐based Real‐Time Assimilative Model (IRTAM) produces coefficients in a similar format as CCIR/URSI coefficients, the PyIRI computational approach was extended to work with IRTAM coefficients. This technical note describes the PyIRTAM software and provides usage examples. The PyIRTAM tool is made publicly available through PyPI and GitHub.

ABSTRACT Objective To evaluate the rate of instrument‐assisted deliveries among parturient patients hospitalized for live, vaginal births across 5 years and test for factors influencing the use of this procedure. Methods Hospitalizations of pregnant people age 18 years or older presenting for a live vaginal birth between October 2017 and 2022 were included for gestational ages between 35.0 and 42.0 weeks. The outcome measured the presence of neonatal instrument‐assisted birth utilizing forceps or a vacuum. Independent variables tested as influencing the outcome included hospitalization year, maternal age, BMI, parity, gestational age, admission to birth time, labor induction, neonate weight, intrapartum analgesia, gestational diabetes and preeclampsia. Descriptive, bivariate and multivariate statistics were conducted in Excel to compare those with and without instrument‐assisted birth. Results The descriptive analysis demonstrated that cases receiving an instrument‐assisted birth had significantly longer admission to birth time (17.8 h [SD = 11.0] vs. 14.1 h [SD = 14.5], p

Aspen exists as the most abundant and industrially important forest type in contemporary Minnesota. Historically, the species was seen as economically undesirable yet saw prolific increases in abundance due to pine harvest and fire. The Leech Lake Reservation exists as a unique case study of tribal-U.S. Forest Service co-management, with 90 % of reservation land within Chippewa National Forest boundaries. This large geographical intersection was created by a series of American Indian law policies and makes the relationship between the Chippewa National Forest and the Leech Lake Band of Ojibwe unique within the USDA National Forest System. Comparison of pre-reservation and more modern forest/land cover types within the modern-day boundaries of the Leech Lake Reservation were conducted alongside investigation of historical management authority documentation of Chippewa National Forest and Leech Lake Band of Ojibwe cooperation and broader historical management of aspen in Minnesota. Results suggest historical power dynamics between the Chippewa National Forest and Leech Lake Band of Ojibwe influenced decreasing pine and increasing aspen on the Leech Lake Reservation. However, the modern relationship between the Chippewa National Forest and the Leech Lake Band of Ojibwe shows the potential for successful co-management within the shared goals of aspen management.

Background: Rugby league is a popular collision sport among Australian adolescent and young adult men. Concussion is one of the more common injuries in rugby league. Few studies have examined concussion in youth rugby league. To examine medically diagnosed concussions from a single season within two elite-level pathway rugby league competitions by evaluating game play risk factors and conducting a video review of potential concussion signs. Methods: All players involved in the Queensland Rugby League's (QRL) under 18 years and under 20 years age group competitions during the 2019 season were included in this study. Data included all head injury assessments (HIAs) identified in real-time through the QRL injury surveillance system for these two QRL age group competitions. The purpose of this study was to (i) report the rates of HIAs and medically diagnosed concussions; (ii) examine video signs of potential concussion; (iii) review game play risk factors related to HIAs and concussions; and (iv) determine the number of days until a concussed player returned to match play and the number of subsequent games missed by concussed players. Results: There were 86 HIAs and 30 medically diagnosed concussions from the two competitions. The concussion incidence was 2.93 per 1000 player match hours in the under 18-year age group and 5.75 per 1000 player match hours in the under 20-year age group. Slow to stand was the most commonly observed video sign (78.6%; 22/28 concussions). Most concussed players (91%, 21/23) missed at least one subsequent game (M ​= ​1.4, SD ​= ​1.7, range ​= ​0–7 games), with the average days to return-to-play being 15.7 (SD ​= ​7.0, range ​= ​7–41 days). Conclusions: In elite-level pathway rugby league, the incidences of HIAs and medically diagnosed concussions were higher in the under 20 age group than the under 18 age group. Both age groups had lower incidences of HIAs and concussions than professional adult rugby league players. Return-to-play following concussion was similar across the two age groups and differed considerably compared to the elite level, with a longer time before return to play for the younger elite level development pathway players.

The pupil is modulated by luminance, arousal, bottom-up sensory, and top-down cognitive signals, and has increasingly been used to assess these aspects of brain functioning in health and disease. However, changes in pupil dynamics across the lifespan have not been extensively examined, hindering our ability to fully utilize the pupil in probing these underlying neural processes in development and aging in healthy and clinical cohorts. Here, we examined pupil responses during the interleaved pro−/anti-saccade task (IPAST) in healthy participants across the lifespan (n = 567, 5–93 years of age). Based on the extracted measurements of pupil dynamics, we demonstrated age-related changes in pupil measures and task modulation. Moreover, we characterized the underlying factors and age-related effects in components of pupil responses that may be attributed to developmental and aging changes in the associated brain regions. Finally, correlations between factors of pupil dynamics and saccade behaviors revealed evidence of shared neural processes in the pupil and saccade control circuitries. Together, these results demonstrate changes in pupil dynamics as a result of development and aging, providing a baseline with which altered pupil responses due to neurological deficits at different ages can be studied.

Gender-based violence (GBV) poses a significant concern in the construction and natural resources industries, where women, due to lower social status and integration, are at heightened risk. This systematic review aimed to identify the prevalence and experience of GBV in the construction and natural resources industries. A systematic search across databases including PubMed, OVID, Scopus, Web of Science, and CINAHL was conducted. The Risk of Bias Instrument for Cross-sectional Surveys of Attitudes and Practices by McMaster University and the Critical Appraisal of Qualitative Studies by the Center for Evidence Based Medicine at the University of Oxford were used to assess the studies included in the review. Six articles were included after full-text analysis. GBV was reported in the construction, mining, urban forestry, and arboriculture sectors. Workplace GBV was measured differently across the studies, and all studies examined more than one form of GBV. The main forms of GBV discussed in these studies were discrimination, sexual harassment, and sexism. The studies provided some insight for demographic factors that may or may not be associated with GBV, such as age, region of work, and number of years working in the industry. The review also suggests that workplace GBV has a negative impact on mental health and well-being outcomes, such as higher levels of stress and lower job satisfaction. The current research has not established the effectiveness of interventions, tools, or policies in these workplaces. Thus, additional research should include intervention studies that aim to minimize or prevent GBV in male-dominated workplaces. The current study can bring awareness and acknowledgement towards GBV in the workplace and highlight the importance of addressing it as this review outlines the negative consequences of GBV on mental health and well-being in these male-dominated industries.

Abstract Objective We aim to discuss the demographics, symptoms, bacteriology, treatment, and sequelae associated with nasal septal hematoma/nasal septal abscess (NSH/NSA). Data Sources CINAHL, PubMed, and Scopus were searched from inception until October 15, 2023. Review Methods Preferred Reporting Items for Systematic Reviews and Meta‐analysis 2020 guidelines were followed. Inclusion criteria included patients who were diagnosed with a traumatic NSH/NSA. NSH/NSA due to surgical procedures was excluded. Demographics included N of patients, patient age, and gender. Symptoms, antibiotics given, bacteriology, and sequelae were analyzed. Meta‐analysis of continuous measures (mean, median), and proportions (%) with a 95% confidence interval (CI) was conducted. Results Thirty studies (N = 598) were included. In total, 72.1% were males (95% CI: 67‐78). The total mean age was 21.6 years (range: 0.2‐85, 95% CI: 17.2‐26.1). The mean time from trauma to diagnosis was 8.2 days. Common symptoms at presentation included nasal obstruction/congestion at 60.3% (95% CI: 37.1‐81.4), nasal pain at 30.0% (17.2‐44.6), swelling at 20.4% (8.7‐35.5), headache at 15.5% (7.3‐26.0), and fever at 13.9% (7.3‐22.2). The most common pathogens isolated included Staphylococcus aureus at 56.5% (49.0‐63.8), Streptococcus species at 8.9% (5.2‐14.0), and Klebsiella pneumoniae at 6.3% (3.2‐10.8). Antibiotics given included amoxicillin‐clavulanate at 10.3% (4.5‐18.2), metronidazole at 9.5% (1.1‐24.9), ampicillin‐sulbactam at 8.9% (0.4‐26.5), and unspecified antibiotics at 39.7% (13.8‐69.2). The most common sequelae were nasal septal deformity/cartilage destruction at 14.3% (7.7‐22.6). Conclusion NSA/NSH has an 8‐day delay in diagnosis from the time of trauma. First‐line practitioners should be made aware of the signs and symptoms of this condition to minimize the risk of morbidity.

Microplastics (MPs) have emerged as widespread environmental pollutants, causing significant threats to aquatic ecosystems and organisms. This review examines the toxic effects of MPs on fishes, with a focus on neurobehavioural, physiological, and reproductive impacts, as well as the underlying mechanisms of toxicity. Evidence indicates that MPs induce a range of neurobehavioural abnormalities in fishes, affecting social interactions and cognitive functions. Altered neurotransmitter levels are identified as a key mechanism driving behavioural alterations following MP exposure. Physiological abnormalities in fishes exposed to MPs are also reported, including neurotoxicity, immunotoxicity, and oxidative stress. These physiological disruptions can compromise the individual health of aquatic organisms. Furthermore, reproductive abnormalities linked to MP exposure are discussed, with a particular emphasis on disruptions in endocrine signaling pathways. These disruptions can impair reproductive success in fish species, impacting population numbers. Here we explore the critical role of endocrine disruptions in mediating reproductive effects after exposure to MPs, focusing primarily on the hypothalamic-pituitary-gonadal axis. Our review highlights the urgent need for interdisciplinary research efforts aimed at elucidating the full extent of MP toxicity and its implications for aquatic ecosystems. Lastly, we identify knowledge gaps for future research, including investigations into the transgenerational impacts, if any, of MP exposure and quantifying synergetic/antagonistic effects of MPs with other environmental pollutants. This expanded knowledge regarding the potential risks of MPs to aquatic wildlife is expected to aid policymakers in developing mitigation strategies to protect aquatic species.

Consensus criteria for traumatic encephalopathy syndrome (TES) specify that at least one core clinical feature of cognitive impairment (CI; e.g., difficulties with memory, executive function) or neurobehavioral dysregulation (ND; e.g., explosiveness, rage, and mood lability) be present and not fully accounted for by other health disorders. Associations between self-reported symptoms that mirror the core clinical features of TES?and how they may be related to concomitant medical conditions?remain unclear. The purpose of this study was to evaluate the association of medical conditions and football exposures with TES clinical features (CI+/?, ND+/?) in 1741 former professional American-style football (ASF) players (age, 57.7???13.9 years; professional seasons, 6.6???3.9 years). Demographics (age, race/ethnicity, current body mass index, age of first football exposure, use of performance-enhancing drugs, position played, and past concussion symptoms), self-reported medical conditions (anxiety, depression, attention-deficit hyperactivity disorder [ADHD], sleep apnea, headache, stroke, hypertension, heart disease, high cholesterol, erectile dysfunction, and low testosterone) were collected. Of 1741 participants, 7.4% were CI+ and/or ND+ (n?=?129). Participants who were CI+ or ND+ were more likely to report one or more coexisting medical conditions than participants who did not report CI or ND (odds ratio [OR]?=?2.04; 95% confidence interval: 1.25?3.47; p?=?0.003). Separate general linear models for each medical condition that adjusted for demographics and football-related factors identified significant associations between ADHD, diabetes, erectile dysfunction, headaches, sleep apnea, anxiety, and low testosterone and CI+ and/or ND+ (ORs?=?1.8?6.0). Chi-square automatic interaction detection (CHAID) multi-variable decision tree models that incorporated medical conditions and football exposures accurately differentiated former players meeting either CI or ND clinical criteria from those meeting none (accuracy?=?91.2?96.6%). CHAID identified combinations of depression, headache, sleep apnea, ADHD, and upper quartiles of concussion symptom history as most predictive of CI+ and/or ND+ status. CI+ and/or ND+ players were more likely to report medical conditions known to cause cognitive symptoms. Concussion exposure and medical conditions significantly increased the likelihood that a former ASF player would demonstrate cognitive or neurobehavioral dysfunction. Clinicians engaged with this population should consider whether treatable coexisting condition(s) could account for some portion of the clinical picture associated with TES presentation.

Motorists are required to interact with both roadway infrastructure and various users. The complexity of the driving task in certain scenarios can influence the frequency and severity of crashes. Turning vehicles at intersections, for example, pose a collision risk for both motorized and non-motorized road users. The primary goal of this paper is to investigate the underlying factors which contribute to right-turn crashes at signalized intersections. Five years of crash data across Oregon were collected. A random parameters binary logit model was developed to predict the likelihood of whether a crash resulted in an injury or fatality. It was found that 14 variables were statistically significant in contributing to crash severity. The results obtained show that dry conditions and a posted speed limit of 30 mi/hr or 35 mi/hr contributed to a higher percentage of severe crashes, while fixed-object crashes and snowy weather had a higher likelihood of resulting in no injury crashes. Time-of-day (9:00 p.m. to 6:00 a.m.), lighting conditions (dusk), gender (male driver), crash type (vehicle–pedestrian and rear-end), and driver-level crash cause (driver sped too fast for conditions, driver did not yield right-of-way, and driver disregarded the traffic control device) all led to an increase in probability of a fatal or injury crash. The vehicle–pedestrian conflict variable had the highest impact on increasing the probability of such a crash while turning right at a signalized intersection. This observation is important because right turns are often permitted during the pedestrian walk and clearance indications, and often drivers do not give right-of-way to pedestrians.

African swine fever (ASF) is a lethal disease of domestic pigs that is currently challenging swine production in large areas of Eurasia. The causative agent, ASF virus (ASFV), is a large, double-stranded and structurally complex virus. The ASFV genome encodes for more than 160 proteins; however, the functions of most of these proteins are still in the process of being characterized. The ASF gene R298L, which has previously been characterized as able to encode a functional serine protein kinase, is expressed late in the virus infection cycle and may be part of the virus particle. There is no description of the importance of the R298L gene in basic virus functions such as replication or virulence in the natural host. Based on its evolution, it is proposed that there are four different phenotypes of R298L of ASFV in nature, which may have potential implications for R298L functionality. We report here that a recombinant virus lacking the R298L gene in the Georgia 2010 isolate, ASFV-G-∆R298L, does not exhibit significant changes in its replication in primary cultures of swine macrophages. In addition, when experimentally inoculated in pigs, ASFV-G-∆R298L induced a fatal form of the disease similar to that caused by the parental virulent ASFV-G. Therefore, deletion of R298L does not significantly affect virus replication and virulence in domestic pigs of the ASFV Georgia 2010 isolate.

Coronavirus disease 2019 (COVID-19) still causes death in elderly and immunocompromised individuals, for whom the sustainability of the vaccine response may be limited. Antiviral treatments, such as remdesivir or molnupiravir, have demonstrated limited clinical efficacy. Nirmatrelvir, an acute respiratory syndrome coronavirus 2 (SARS-CoV-2) major protease inhibitor, is clinically effective but has been associated with viral rebound and antiviral resistance. It is thus necessary to study novel and repurposed antivirals for the treatment of COVID-19. We previously demonstrated that daclatasvir (DCV), an inhibitor of the hepatitis C virus (HCV) NS5A protein, impairs SARS-CoV-2 replication by targeting viral RNA polymerase and exonuclease, but the doses of DCV used to inhibit the new coronavirus are greater than the standard human plasma exposure for hepatitis C. Because any potential use of DCV against SARS-CoV-2 would be shorter than that reported here and short-term toxicological studies on DCV show that higher doses are tolerable, we searched for doses of DCV that could protect transgenic mice expressing the human ACE2 receptor (K18-hACE-2) from lethal challenge with SARS-CoV-2. We found that a dose of 60 mg/kg/day provides this protection by reducing virus replication and virus-induced lung insult. This dose is tolerable in different animal models. Taken together, our data provide preclinical evidence that can support phase I clinical trials to confirm the safety, tolerability, and pharmacokinetics of new doses of daclatasvir for a short duration in humans to further advance this compound’s utility against COVID-19.

Abstract ANCHOR is a novel assimilative model developed at the U.S. Naval Research Laboratory, which was designed for rapid assimilative runs. ANCHOR uses recently developed PyIRI model for the background and for the formation of the background covariance matrix. It only takes a few minutes for ANCHOR to complete the data assimilation (DA) for one day, including data pre‐processing and model set up. ANCHOR extracts ionospheric parameters from radio occultation (RO) and ionosonde data using PyIRI formalism and assimilates them as point measurements into maps of the background parameters using a Kalman Filter approach. This paper introduces the ANCHOR algorithm, discusses its coordinate system and background, explains the background covariance formation, discusses the extraction of the ionospheric parameters from the data and the assimilation process, and, finally, shows the results of the observing system simulation experiment with synthetic data simulated using the SAMI3 model. ANCHOR reduces the root mean square errors in the analysis by more than a half for all of the ionospheric parameters in comparison to the background. Finally, this paper discusses advantages and limitations of the parametrized ionospheric DA, highlighting the avenues for its future improvement.

IMPORTANCE:. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has evolved through multiple phases in the United States, with significant differences in patient centered outcomes with improvements in hospital strain, medical countermeasures, and overall understanding of the disease. We describe how patient characteristics changed and care progressed over the various pandemic phases; we also emphasize the need for an ongoing clinical network to improve the understanding of known and novel respiratory viral diseases. OBJECTIVES:. To describe how patient characteristics and care evolved across the various COVID-19 pandemic periods in those hospitalized with viral severe acute respiratory infection (SARI). DESIGN:. Severe Acute Respiratory Infection-Preparedness (SARI-PREP) is a Centers for Disease Control and Prevention Foundation-funded, Society of Critical Care Medicine Discovery-housed, longitudinal multicenter cohort study of viral pneumonia. We defined SARI patients as those hospitalized with laboratory-confirmed respiratory viral infection and an acute syndrome of fever, cough, and radiographic infiltrates or hypoxemia. We collected patient-level data including demographic characteristics, comorbidities, acute physiologic measures, serum and respiratory specimens, therapeutics, and outcomes. Outcomes were described across four pandemic variant periods based on a SARS-CoV-2 sequenced subsample: pre-Delta, Delta, Omicron BA.1, and Omicron post-BA.1. SETTING:. Multicenter cohort of adult patients admitted to an acute care ward or ICU from seven hospitals representing diverse geographic regions across the United States. PARTICIPANTS:. Patients with SARI caused by infection with respiratory viruses. MAIN OUTCOMES AND RESULTS:. Eight hundred seventy-four adult patients with SARI were enrolled at seven study hospitals between March 2020 and April 2023. Most patients (780, 89%) had SARS-CoV-2 infection. Across the COVID-19 cohort, median age was 60 years (interquartile range, 48.0–71.0 yr) and 66% were male. Almost half (430, 49%) of the study population belonged to underserved communities. Most patients (76.5%) were admitted to the ICU, 52.5% received mechanical ventilation, and observed hospital mortality was 25.5%. As the pandemic progressed, we observed decreases in ICU utilization (94% to 58%), hospital length of stay (median, 26.0 to 8.5 d), and hospital mortality (32% to 12%), while the number of comorbid conditions increased. CONCLUSIONS AND RELEVANCE:. We describe increasing comorbidities but improved outcomes across pandemic variant periods, in the setting of multiple factors, including evolving care delivery, countermeasures, and viral variants. An understanding of patient-level factors may inform treatment options for subsequent variants and future novel pathogens.

Abstract In a warming climate, an intensifying fire regime and higher likelihood of extreme rain are expected to increase watershed sediment yield in many regions. Understanding regional variability in landscape response to fire and post‐fire rainfall is essential for managing water resources and infrastructure. We measured sediment yield resulting from sequential wildfire and extreme rain and flooding in the upper Carmel River watershed (116 km2), on the central California coast, USA, using changes in sediment volume mapped in a reservoir. We determined that the sediment yield after fire and post‐fire flooding was 854–1,100 t/km2/yr, a factor of 3.5–4.6 greater than the long‐term yield from this watershed and more than an order of magnitude greater than during severe drought conditions. In this first large‐scale field validation test of the WEPPcloud/wepppy framework for the Water Erosion Prediction Project (WEPP) model on a burned landscape, WEPP predicted 81%–106% of the measured sediment yield. These findings will facilitate assessing and predicting future fire effects in steep watersheds with a Mediterranean climate and indicate that the increasingly widespread use of WEPP is appropriate for evaluating post‐fire hillslope erosion even across 100‐km2 scales under conditions without debris flows.

The movement ecology of Bull Trout (Salvelinus confluentus) in watersheds at the northern geographic range extent is not well understood. We implanted 54 Bull Trout with acoustic transmitters in the Prairie Creek watershed, Northwest Territories, Canada and tracked fish from July 2011 to October 2012 using 19 stationary hydrophones. Bull Trout movement patterns generally corresponded to two groups, as a result of individual variation within and across seasons. The first group exhibited seasonal variations in movement and habitat use, moving most (range 11.7–115.9 km) and occupying the largest home ranges in summer and autumn, while exhibiting little movement during winter and spring. The second group made negligible movements within seasons and resided in localized areas. Restricted movement in winter resulted in a severe range contraction. The average distance moved within a season was 11.5 km (range 0.3–64.9 km per fish). The unusually high prevalence of stationarity in this watershed suggest fish can complete all life processes (spawning, feeding, and rearing) in short reaches (

Abstract Background Understanding of Long COVID has advanced through patient-led initiatives. However, research about barriers to accessing Long COVID services is limited. This study aimed to better understand the need for, access to, and quality of, Long COVID services. We explored health needs and experiences of services, including ability of services to address needs. Methods Our study was informed by the Levesque et al.’s (2013) “conceptual framework of access to health care.” We used Interpretive Description, a qualitative approach partly aimed at informing clinical decisions. We recruited participants across five settings. Participants engaged in one-time, semi-structured, virtual interviews. Interviews were transcribed verbatim. We used reflexive thematic analysis. Best practice to ensure methodological rigour was employed. Results Three key themes were generated from 56 interviews. The first theme illustrated the rollercoaster-like nature of participants’ Long COVID symptoms and the resulting impact on function and health. The second theme highlighted participants’ attempts to access Long COVID services. Guidance received from healthcare professionals and self-advocacy impacted initial access. When navigating Long COVID services within the broader system, participants encountered barriers to access around stigma; appointment logistics; testing and ‘normal’ results; and financial precarity and affordability of services. The third theme illuminated common factors participants liked and disliked about Long COVID services. We framed each sub-theme as the key lesson (stemming from all likes and dislikes) that, if acted upon, the health system can use to improve the quality of Long COVID services. This provides tangible ways to improve the system based directly on what we heard from participants. Conclusion With Long COVID services continuously evolving, our findings can inform decision makers within the health system to better understand the lived experiences of Long COVID and tailor services and policies appropriately.

Abstract We require a better understanding of the relative contribution of different modes of non-genetic inheritance in behavioral trait development. Thus, we investigate variation in exploratory behavior, which is ecologically relevant and a target of selection. The metabolic hypothesis predicts exploratory behavior to be size-dependent across taxa. This size-dependency is cancelled out under high perceived risk, allowing us to determine the transgenerationally integrated estimated level of risk. Using fathead minnows Pimephales promelas, we manipulated perceived risk in mothers, fathers, caring males and offspring through continuous exposure to either conspecific alarm cues or to a control water treatment. In 1000 four-month old offspring, we determined body sizes and exploratory behavior. Perceived high risk in mothers, followed by personal risk, was most effective in eliminating size-dependent behavior whereas effects of paternal risk on offspring behavioral development were substantially weaker. When maternal risk is high, environmental mismatches between parents prevented offspring from responding appropriately to personal high risk. The environment of the caring male also impacted offspring behavior to a greater extent than that of its genetic parents. Our study highlights the high relative importance of maternal, personal and caring male risk environments and showcases potential costs of an environmental mismatch between parental sexes.