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Abstract Few studies have reported on the accuracy of self‐reported hypertension history among older postmenopausal women, which was this study's objective. Participants were postmenopausal women enrolled in the Osteoporosis and Periodontal Disease (OsteoPerio) study, an ancillary investigation of the Women's Health Initiative Observational Study (WHI‐OS) at the Buffalo, New York, clinical site. Participants self‐reported their history of physician diagnosed hypertension treated with medication at WHI‐OS enrollment (1993–1998; n = 1342, mean age 63 years), then 3 years later at OsteoPerio enrollment (1997–2001; n = 1342), and again at OsteoPerio Year 5 follow‐up (2002–2005; n = 1020). At each time point, medication inventories were recorded and served as the criterion with which self‐report was compared in the present study. Physician diagnosed‐treated hypertension was also self‐reported annually on mailed health update questionnaires in the WHI‐OS and were compared against medication inventory at the subsequent clinic exam. Of those participants who self‐reported a history of hypertension at WHI enrollment, OsteoPerio enrollment, and OsteoPerio Year 5 follow‐up, 41.2%, 90.3%, and 94.4%, respectively, had anti‐hypertensive pills in their medication inventory. Across the three time points, sensitivity and specificity ranged from 0.72 to 0.98 and from 0.85 to 0.95, and kappa coefficients ranged from 0.52 to 0.79 when comparing self‐report with medication inventory. For self‐reported newly physician‐diagnosed and treated hypertension on the annual health update questionnaire, 88.4% and 95.2% of those reporting hypertension had anti‐hypertensive pills in the subsequent medication inventory. In general, sensitivity and kappa were lower in women aged ≥70 versus

Abstract This research examined the impact of aerobic exercise intensity and dose on acute post‐exercise cerebral shear stress and blood flow. Fourteen young adults (27 ± 5 years of age, eight females) completed a maximal oxygen uptake (V̇O2max) treadmill test followed by three randomized study visits: treadmill exercise at 30% of V̇O2max for 30 min, 70% of V̇O2max for 30 min and 70% of V̇O2max for a duration that resulted in caloric expenditure equal to that in the 30% V̇O2max visit (EqEE). A venous blood draw and internal carotid artery (ICA) ultrasound were collected before and immediately following exercise. ICA diameter and blood velocity were determined using automated edge detection software, and blood flow was calculated. Using measures of blood viscosity, shear stress was calculated. Aerobic exercise increased ICA shear stress (time: P = 0.005, condition: P = 0.012) and the increase was greater following exercise at 70% V̇O2max (∆4.1 ± 3.5 dyn/cm2) compared with 30% V̇O2max (∆1.1 ± 1.9 dyn/cm2; P = 0.041). ICA blood flow remained elevated following exercise (time: P = 0.002, condition: P = 0.010) with greater increases after 70% V̇O2max (Δ268 ± 150 mL/min) compared with 30% V̇O2max (∆125 ± 149 mL/min; P = 0.041) or 70% V̇O2max EqEE (∆127 ± 177 mL/min; P = 0.004). Therefore, aerobic exercise resulted in both intensity‐ and dose‐dependent effects on acute post‐exercise ICA blood flow whereby vigorous intensity exercise provoked a larger increase in ICA blood flow compared to light intensity exercise when performed at a higher dose.

Abstract Aims New tools are needed to identify heart failure (HF) risk earlier in its course. We evaluated the association of multidimensional cardiopulmonary exercise testing (CPET) phenotypes with subclinical risk markers and predicted long‐term HF risk in a large community‐based cohort. Methods and results We studied 2532 Framingham Heart Study participants [age 53 ± 9 years, 52% women, body mass index (BMI) 28.0 ± 5.3 kg/m2, peak oxygen uptake (VO2) 21.1 ± 5.9 kg/m2 in women, 26.4 ± 6.7 kg/m2 in men] who underwent maximum effort CPET and were not taking atrioventricular nodal blocking agents. Higher peak VO2 was associated with a lower estimated HF risk score (Spearman correlation r: −0.60 in men and −0.55 in women, P

Abstract Objective The hippocampus plays a critical role in cognitive networks. The anterior hippocampus is vulnerable to early‐life stress and socioeconomic status (SES) with alterations persisting beyond childhood. How SES modifies the relationship between early hippocampal development and cognition remains poorly understood. This study examined associations between SES, structural and functional development of neonatal hippocampus, and 18‐month cognition in very preterm neonates. Methods In total, 179 preterm neonates were followed prospectively. Structural and resting‐state functional MRI were obtained early‐in‐life and at term‐equivalent age (median 32.9 and 41.1 weeks post‐menstrual age) to calculate anterior and posterior hippocampal volumes and hippocampal functional connectivity strength. Eighteen‐month cognition was assessed via Bayley‐III. Longitudinal statistical analysis using generalized estimating equations, accounting for birth gestational age, post‐menstrual age at scan, sex, and motion, was performed. Results SES, measured as maternal education level, modified associations between anterior but not posterior hippocampal volumes and 18‐month cognition (interaction term p = 0.005), and between hippocampal connectivity and cognition (interaction term p = 0.05). Greater anterior hippocampal volumes and hippocampal connectivity were associated with higher cognitive scores only in the lowest SES group. Maternal education alone did not predict neonatal hippocampal volume from early‐in‐life and term. Interpretation SES modified the relationship between neonatal hippocampal development and 18‐month cognition in very preterm neonates. The lack of direct association between maternal education and neonatal hippocampal volumes indicates that socio‐environmental factors beyond the neonatal period contribute to modifying the relationship between hippocampal development and cognition. These findings point toward opportunities to more equitably promote optimal neurodevelopmental outcomes in very preterm infants.

Objective Our objective was to describe the administration of glucocorticoids (GCs) and characterize its association with organ damage in a longitudinal systemic lupus erythematosus (SLE) cohort over a time period spanning the introduction of biologics in Canada. Methods A retrospective observational study was conducted using data from a large SLE cohort in Canada, including adults without lupus nephritis or central nervous system lupus. Patients were observed from time of entry into the cohort to the last available clinic visit (up to December 31, 2020), with a minimum of 24 months of follow‐up. Demographic and clinical characteristics, including average disease activity, treatment administration, and prevalence of organ damage, were examined. Organ damage was stratified by GC administration. Results A total of 1,255 patients were included. The mean follow‐up duration was 10.5 (SD 8.6) years. One hundred eighty‐two (15%) patients had organ damage at baseline. More than 80% of patients were prescribed GCs over the follow‐up period, almost all patients had long‐term GC treatment, and only 5% of patients took any biologics. Organ damage was more frequent in patients with a higher average GC dose and greater years of GC exposure. Conclusion In this large cohort of patients with SLE, the majority of patients continue to rely on GC for SLE symptom management, with limited administration of biologics. GC administration was correlated with increased irreversible organ damage. Access to novel GC‐sparing treatment options is critical to improve long‐term outcomes for patients with SLE, especially given the continued reliance on GC despite the introduction of biologics.

Abstract An 8‐year‐old female spayed German shepherd dog was presented for evaluation of a 1‐week history of right thoracic limb monoparesis. Magnetic resonance imaging (MRI) identified an intraparenchymal, T2 hypointense and T1 isointense, strongly heterogeneously contrast‐enhancing mass with moderate internal susceptibility artifact on T2* images at the level of the cranial extent of the C5 vertebral body. Euthanasia was elected after a rapid neurologic decline in the 24 hours after MRI. Necropsy and histopathology identified an intraparenchymal hemangiosarcoma arising from a hemangioma in the cervical spinal cord, with no evidence of neoplastic disease in any other examined organs. The spectrum of vasoproliferative disorders in the central nervous system in veterinary species has been codified recently, but hemangiosarcoma is considered metastatic to the central nervous system. Herein we describe the clinical, imaging, and histologic findings in a dog with a novel primary location of hemangiosarcoma in the cervical spinal cord.

Abstract Background Fibroblast growth factor 19 (FGF19) is an enterohepatic hormone the synthesis of which is stimulated by bile acid activation of the nuclear farnesoid X receptor (FXR) in ileal enterocytes. Increased production of FGF19 downregulates hepatocyte bile acid synthesis and gluconeogenesis, while concurrently upregulating hepatocyte glycogenesis and gallbladder (GB) filling. The physiologic impact of this regulatory cycle is illustrated in cholecystectomized humans, in whom the disturbed meal‐related flux of GB bile decreases serum FGF19 concentrations. Objective Determine if serum FGF19 concentrations are lower in dogs with clinical GB mucoceles (GBMs) than in control dogs. Animals Seven dogs with GBM diagnosed using abdominal ultrasonography, biochemical markers, and GB histopathology. Forty‐two control dogs without gastrointestinal or hepatobiliary disorders also were evaluated. Health status of controls was assessed by physical examination and diagnostic hematologic and biochemical test results. Methods Prospective cross‐sectional study to compare fasting plasma or serum FGF19 concentrations between groups. Concentrations of FGF19 were quantified by a commercially available FGF19 ELISA. Results Concentrations of FGF19 were significantly lower in dogs with clinical GBM (median, 14.0 pg/mL; range, 12.8‐67.2) than in control dogs (median, 145.3 pg/mL; range, 36.5‐285.1). Conclusions and Clinical Importance In dogs, GBM is associated with significantly decreased serum FGF19 concentrations. We speculate that this finding reflects compromised GB contraction and decreased enterohepatic circulation of bile flow. Subnormal FGF19 concentrations may influence bile acid synthesis and hepatic metabolism.

Abstract Objectives This work aims to determine the efficacy and safety of preoperative alpha‐blocker therapy on ureteroscopy (URS) outcomes. Methods In this systematic review and meta‐analysis of randomised trials of URS with or without preoperative alpha‐blocker therapy, outcomes included the need for ureteral dilatation, stone access failure, procedure time, residual stone rate, hospital stay, and complications. Residual stone rates were reported with and without adjustments for spontaneous stone passage, medication noncompliance, or adverse events leading to patient withdrawal. Data were analysed using random‐effects meta‐analysis and meta‐regression. Certainty of evidence was assessed using the GRADE criteria. Results Among 15 randomised trials with 1653 patients, URS was effective and safe with a stone‐free rate of 81.2% and rare (2.3%) serious complications. The addition of preoperative alpha‐blockers reduced the need for ureteral dilatation (risk ratio [RR] = 0.48; 95% CI = 0.30 to 0.75; p = 0.002), access failure rate (RR = 0.36; 95% CI = 0.23 to 0.57; p

Abstract Objective Mid‐life cardiovascular risk factors are associated with later cognitive decline. Whether repetitive head injury among professional athletes impacts cardiovascular risk is unknown. We investigated associations between concussion burden and postcareer hypertension, high cholesterol, and diabetes among former professional American‐style football (ASF) players. Methods In a cross‐sectional study of 4080 professional ASF players conducted between January 2015 and March 2022, we used an mulitsymptom concussion symptom score (CSS) and the number of loss‐of‐consciousness (LOC) episodes as a single severe symptom to quantify football‐related concussion exposure. Primary outcomes were hypertension, dyslipidemia, and diabetes, defined by current or recommended prescription medication use. Results The prevalence of hypertension, high cholesterol, and diabetes among former players (52 ± 14 years of age) was 37%, 34%, and 9%. Concussion burden was significantly associated with hypertension (lowest vs. highest CSS quartile, odds ratio (OR) = 1.99; 95%CI: 1.33–2.98; p

Abstract Methotrexate (MTX) doses on days +1, +3, +6, and +11 after match unrelated donor allogeneic stem cell transplant (MUD HSCT) is a common graft‐versus‐host disease (GVHD) prophylaxis regimen. However, the overlapping toxicity of MTX with conditioning chemotherapy sometimes warrants the omission of the fourth dose of MTX. Prior single‐institution studies showed conflicting results comparing the outcomes of patients who received three versus four doses of MTX, but to our knowledge, the effect of concomitant antithymocyte globulin (ATG) has not been reported. Charts of patients who underwent MUD HSCT between 2009 and 2023 were reviewed. Patients received rabbit ATG (Thymoglobulin), given at 0.5 mg/kg on day −3, 2 mg/kg on day −2, and 2.5 mg/kg on day −1. MTX is given at 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6, and +11. Severe mucositis was the most common indication for day +11 MTX omission (82%). We identified 292 patients (116 in 3 dose cohort and 176 in 4 dose cohort). Median follow‐up was 23 months (range 1–151). Patients in the 4 doses cohort were more frequently male (68% vs. 50%, p

Objective We aimed to estimate Coccidioides serologic screening rates before initiation of biologic disease‐modifying antirheumatic drugs including tofacitinib (b/tsDMARDs), conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs), and/or noninhaled corticosteroids. Methods This retrospective cohort study used 2011 to 2016 US Medicare claims data and included beneficiaries with rheumatic or autoimmune disease residing in regions within Arizona, California, and Texas endemic for Coccidioides spp. with ≥1 prescription for a b/tsDMARD, csDMARD, and/or noninhaled corticosteroid. We estimated prior‐year serologic screening incidence before initiating b/tsDMARDs, csDMARD, and/or noninhaled corticosteroid. Results During 2012 to 2016, 4,331 beneficiaries filled 64,049 prescriptions for b/tsDMARDs, csDMARDs, and noninhaled corticosteroids. Arizona's estimated screening rate was 20.1% (95% confidence interval [95% CI] 14.5–25.7) in the year before prescription initiation for b/tsDMARDs, 8.1% (95% CI 6.5–9.7) before csDMARDs, and 6.9% (95% CI: 5.6–8.2) before corticosteroids. Screening rates for b/tsDMARDs (2.8%, 95% CI 0.0–6.7), csDMARDs (1.0%, 95% CI 0.0–2.0), and corticosteroids (0.8%, 95% CI: 0.4–1.1) were negligible in California and undetected in Texas. Adjusted screening rate before prescription for b/tsDMARDs in Arizona increased from 14.5% (95% CI 7.5–21.5) in 2012 to 26.7% (95% CI 17.6–35.8) in 2016. Rheumatologists prescribing b/tsDMARDs in Arizona screened more than other providers (20.9% [95% CI 13.9–27.9] vs 12.9% [95% CI 5.9–20.0]). Conclusion Coccidioides serologic screening rates among Medicare beneficiaries with rheumatic/autoimmune diseases on b/tsDMARDs, csDMARDs, and noninhaled corticosteroids was low in Coccidioides spp.–US endemic regions between 2012 and 2016. Alignment of screening recommendations and clinical practice is needed.

Background Lymphatic disorders such as protein‐losing enteropathy, plastic bronchitis, and chylothorax are important complications of the Fontan circulation and ultimately result in an increased risk of early death. Several European centers are now performing lymphatic procedures. The aim of this study is to map the extent of these lymphatic disorders and treatments provided across European pediatric cardiology centers. Methods and Results A survey was circulated to 49 European pediatric cardiology centers consisting of 37 questions including a mix of binary, categorical, and continuous variables. Thirty‐one centers (63%) participated in the study, performing a median of 250 (interquartile range, 178 ‐ 313) cardiopulmonary bypass procedures per year. Chylothorax emerged as the most prevalent lymphatic disorder followed by protein‐losing enteropathy and plastic bronchitis. The most common diagnostic investigation method was noncontrast magnetic resonance lymphangiography (52%). Eleven centers (35%) conducted lymphatic interventions with a median of 3 (interquartile range, 1 ‐ 4) procedures per year and 12 (interquartile range, 5 ‐ 15) interventions in total per center. Conclusions This study confirms the rarity of and variation in treatment approaches for lymphatic disorders across Europe. With at least 11 centers offering lymphatic interventions, the adoption of these procedures is on the rise in Europe. To improve the quality of care and treatment outcomes for these complex patients, it is crucial to consider evidence‐based lymphatic diagnostics, interventional lymphatic procedures, and the centralization of services in Europe.

ABSTRACT Background The cumulative, health system‐wide survival benefit of immune checkpoint inhibitors (ICIs) is unclear, particularly among real‐world patients with limited life expectancies and among subgroups poorly represented on clinical trials. We sought to determine the health system‐wide survival impact of ICIs. Methods We identified all patients receiving PD‐1/PD‐L1 or CTLA‐4 inhibitors from 2010 to 2023 in the national Veterans Health Administration (VHA) system (ICI cohort) and all patients who received non‐ICI systemic therapy in the years before ICI approval (historical control). ICI and historical control cohorts were matched on multiple cancer‐related prognostic factors, comorbidities, and demographics. The effect of ICI on overall survival was quantified with Cox regression incorporating matching weights. Cumulative life‐years gained system‐wide were calculated from the difference in adjusted 5‐year restricted mean survival times. Results There were 27,322 patients in the ICI cohort and 69,801 patients in the historical control cohort. Among ICI patients, the most common cancer types were NSCLC (46%) and melanoma (10%). ICI demonstrated a large OS benefit in most cancer types with heterogeneity across cancer types (NSCLC: adjusted HR [aHR] 0.56, 95% confidence interval [CI] 0.54–0.58, p

Background Atrial fibrillation (AF) is a known risk factor of ischemic stroke, and AF‐related stroke is twice more likely to be fatal. Long‐term cardiac rhythm monitoring using insertable cardiac monitors (ICMs) has greater diagnostic yield compared with conventional monitoring in detecting AF, and the clinical utility of ICMs is established in cryptogenic stroke, strokes attributable to large‐artery atherosclerosis, and strokes attributable to small‐vessel disease. A registry‐based study was conducted to evaluate the inpatient implantation of ICMs and the feasibility of vascular and interventional neurologists as implanters using novel collaborative clinical care pathway for cryptogenic stroke. Methods Multiyear data from a hospital‐based registry at a comprehensive stroke center were reviewed to evaluate inpatient ICM implantation and test feasibility of vascular and interventional neurologists as implanters of ICMs together with cardiology using a novel collaborative care pathway. Reviewed data included the number of ICMs, implantation trend, inpatient versus outpatient setting, time to ICM implantation, inpatient workflow, including defined roles of team members, and AF detection rate. Results A total of 290 ICMs for cryptogenic stroke were implanted when patients were in the hospital and 78 as outpatients after discharge during the study period of 3 years. Most inpatient ICM implants were performed by vascular and interventional neurology (n = 181), and ICM use for cryptogenic stroke increased by 130%. The average time to inpatient ICM implant was 4.1 days, with 77% in 5 days and 95.5% within 10 days poststroke. The average time to out‐patient ICM placement was 57 days. AF detection rate of 36.5% was noted at 24 months with a collaborative care pathway. Conclusion Inpatient implantation of ICMs is feasible and was performed safely and efficiently by vascular and interventional neurology together with cardiology using a collaborative care pathway. An increase in use of ICMs and higher AF detection rates were noted. Findings support innovative efforts to improve access and close the gaps in the delivery of cryptogenic stroke care to ultimately reduce the secondary stroke burden.

Abstract Management decisions often focus on the habitat selection of marked individuals without considering the contribution to demographic performance in selected habitats. Because habitat selection is not always adaptive, understanding the spatial relationship between habitat selection and demographic performance is critical to management decisions. Mapping both habitat selection and demographic performance for species of conservation concern can help guide population‐scale conservation efforts. We demonstrate a quantitative approach to differentiate areas supporting selection and survival at large spatial extents. As a case study, we applied this approach to greater sage‐grouse (Centrocercus urophasianus; hereafter, sage‐grouse), an indicator species for sagebrush ecosystems. We evaluated both habitat selection and survival across multiple reproductive life stages (nesting, brood‐rearing) in the Bi‐State Distinct Population Segment, a genetically distinct and geographically isolated population of sage‐grouse on the southwestern edge of the species' range. Our approach allowed us to identify both mismatches between selection and survival and trade‐offs between reproductive life stages. These findings suggest resource demands vary across time, with predation risk being a dominant driver of habitat selection during nesting and early brood‐rearing periods when chicks are smaller and flightless, whereas access to forage resources becomes more important during late brood rearing when resources become increasingly limited. Moving beyond identifying and managing habitat solely based on species occupancy or use by incorporating demographic measures allows managers to tailor actions to their specific goals; for example, protections of areas that support high selection and high survival and restoration actions focused on increasing survival in areas of high selection and low survival.

Abstract Fjord systems in the Norwegian Arctic are experiencing an increasing frequency and magnitude of marine heatwaves. These episodic heat stress events can have varying degrees of acute impacts on primary production and nutrient uptake of mixed kelp communities, as well as modifying the biogeochemical cycling in nearshore systems where vast areas of kelp create structural habitat. To assess the impact of future marine heatwaves on kelp communities, we conducted a 23 day mesocosm experiment exposing mixed kelp communities to warming and heatwave scenarios projected for the year 2100. Three treatments were considered: a constant warming (+1.8°C from the control), a medium magnitude and long duration heatwave event (+2.8°C from the control for 13 days), and two short‐term, more intense, heatwaves(5 day long scenarios with temperature peaks at +3.9°C from the control). The results show that both marine heatwave treatments reduced net community production, whereas the constant warm temperature treatment displayed no difference from the control. The long marine heatwave scenario resulted in reduced accumulated net community production, indicating that prolonged exposure had a greater severity than two high magnitude, short‐term heatwave events. We estimated an 11°C temperature threshold at which negative effects to primary production appeared present. We highlight that marine heatwaves can induce sublethal effects on kelp communities by depressing net community production. These results are placed in the context of potential physiological resilience of kelp communities and implications of reduced net community production to future Arctic fjord environmental conditions.

Abstract Developing safe and effective drugs and other medical products is a complex and costly process. Drug development has been, historically, commonly competitive and uncollaborative, and this tendency toward a lack of interaction between stakeholders—the pharmaceutical industry, academia, regulatory agencies, healthcare providers, and communities, among others—can lead to missed opportunities to improve efficiency and, ultimately, public health. The Forum for Collaborative Research was established in 1997 to address current scientific, policy, and regulatory issues in global health through multistakeholder engagement and dialogue. By providing a neutral and safe space for discussion, the Forum's model has impacted how clinical trials in diverse health areas are conducted, supported broader and more equitable clinical trial participation, and accelerated delivery of new drugs. The Forum's focus and directions have shifted over time, and this responsiveness to the needs of the global health community will be critical to ensure that the Forum continues to support collaboration in global health. In this article, we present lessons learned from this innovative model of collaborative research and regulatory science, pioneered by the Forum for over 25 years, including the importance of collective ownership and governance by all stakeholders, and emphasis on common goals and advantages of collaboration.

Abstract Objective The COVID‐19 pandemic required unprecedented changes to emergency medical services (EMS) educational frameworks in the United States. It is unclear if pandemic‐related changes impacted paramedic educational outcomes. We aimed to evaluate curricular and performance changes resulting from the initial COVID‐19 pandemic on paramedic educational programs. Methods We performed a retrospective cross‐sectional evaluation of paramedic educational programs in 2019 and 2020 using the Committee on Accreditation of Educational Programs for the Emergency Medical Services Professions annual reports. These reports contain detailed program components and measures of program success. We included programs reporting at least one graduate in the study period. Descriptive statistics (proportions [%], median [interquartile range, IQR]) were calculated for paramedic program characteristics in 2019 and 2020, as well as pandemic specific curriculum changes. Wilcoxon rank‐sum and Fisher's exact tests were used to evaluate differences in characteristics by year. Results The number of paramedic educational programs in our population decreased from 640 programs in 2019 to 612 in 2020, with a statistically significant decrease in clinical hours (2019: 219 [IQR 168‒272]; 2020: 200.5 [IQR 157‒261]). There was no difference in first or third‐attempt certification examination success between years. Temporary shutdown was experienced in 34% of programs (duration: 3 weeks [2‒7]) and 72% of required curricular changes. Curricular changes commonly included decreased in‐person education (86%), traditional classroom lectures (78%), number of clinical sites (78%), and increased online didactic education (92%). Only 20% of programs decreased laboratory simulation or total training hours. Conclusion During the pandemic, paramedic educational programs changed educational delivery with no observed differences on overall program performance. Identifying key curricular changes and best practices for implementation may be necessary to better optimize future educational delivery.

Abstract Objectives We hypothesized that lactate clearance and reduction of the Sequential Organ Failure Assessment (SOFA) score during patients’ critical care resuscitation unit (CCRU) stay would be associated with lower in‐hospital mortality. Methods This was a retrospective study of adult patients who had sepsis diagnoses and were admitted to the CCRU in 2018. Multivariable logistic regression analysis was performed to assess the association of clinical factors, lactate clearance, and SOFA reduction with hospital mortality. Results A total of 401 patients with lactate clearance data and 455 patients with SOFA score data were included in the study. The mean (SD) lactate and SOFA score on admission were 2.2 (1.8) mmol/L and 4.4 (4.3), respectively. Average lactate clearance was 0.1 (2.6) mmol/L, and average SOFA score reduction was 0.65 (5.9). Patients with a one point reduction in SOFA score during their CCRU stay had a 31% reduction of mortality (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.62–0.77, p

Abstract Early life adversity (ELA) is associated with earlier initiation and maintenance of tobacco smoking and with a greater risk of subsequent relapse. There is growing evidence that appetite hormones, including peptide YY (PYY), which modulates craving and satiety responses, play a role in stress and addiction processes. This study employed a quasi‐experimental design to examine the association between ELA and circulating PYY stress responses in smokers and nonsmokers (N = 152, ages 19–73 years) to examine the effects of nicotine addiction. Smokers initiated a quit attempt as part of the study and were classified as either abstinent smokers or relapsed smokers based on their nicotine use during the follow‐up period. PYY levels were measured at five timepoints during three lab sessions and compared between nonsmokers and the two smoking groups (abstainers, relapsers): while smokers were using nicotine ad libitum, 24 h after smokers initiated a quit attempt, and 4 weeks after smokers initiated a quit attempt. Multivariate analyses showed the main effects of time on PYY, which decreased over time within each session. The main effects of ELA during the first (ad libitum smoking) and second (24‐h post‐cessation for smokers) sessions indicated that experiencing ELA was associated with lower PYY. No systematic effect of nicotine addiction or relapse was observed in this study. These findings suggest that adults with higher ELA may experience lower PYY. Additional research is needed to further explore the role of PYY in stress and addiction processes.

Abstract The innate immune system serves as the body's first line of defense, utilizing pattern recognition receptors like Toll‐like receptors to detect pathogens and initiate rapid response mechanisms. Following this initial response, adaptive immunity provides highly specific and sustained killing of pathogens via B cells, T cells, and antibodies. Traditionally, it has been assumed that innate immunity activates adaptive immunity; however, recent studies have revealed more complex interactions. This review provides a detailed dissection of the composition and function of the innate and adaptive immune systems, emphasizing their synergistic roles in physiological and pathological contexts, providing new insights into the link between these two forms of immunity. Precise regulation of both immune systems at the same time is more beneficial in the fight against immune‐related diseases, for example, the cGAS–STING pathway has been found to play an important role in infections and cancers. In addition, this paper summarizes the challenges and future directions in the field of immunity, including the latest single‐cell sequencing technologies, CAR‐T cell therapy, and immune checkpoint inhibitors. By summarizing these developments, this review aims to enhance our understanding of the complexity interactions between innate and adaptive immunity and provides new perspectives in understanding the immune system.

Abstract Dedicator of cytokinesis 8 (DOCK8) deficiency is a primary immunodeficiency disease caused by mutations in exon 45 of the DOCK8 gene. The clinical signs primarily consist of increased serum IgE levels, eczema, repeated skin infections, allergies, and upper respiratory tract infections. Using CRISPR/Cas9 technology, we generated a DOCK8 exon 45 mutation in mice, mirroring the mutation found in patients. The results indicated that DOCK8 mutation impairs peripheral T cell homeostasis, disrupts regulatory T cells (Tregs) development, increases ICOS expression in Tregs within peripheral lymph nodes (pLn), and promotes Th17 cell differentiation within the spleen and pLn. Upon virus infection, DOCK8 mutation CD4+ T cells have a Th2 effector fate. RNA‐bulk sequencing data revealed alternations in the mTOR pathway of DOCK8 mutant CD4+ T cells. We observed that DOCK8 mutation upregulates the glycolysis levels in CD4+ T cells, which is related to the Akt/mTOR/S6/HIF‐1α pathway. In summary, our research elucidates that DOCK8 regulates the differentiation of helper T cells by modulating the glycolytic pathway in CD4+ T cells, thereby advancing the comprehension and offering potential treatment of diseases in DOCK8‐deficient patients.

Background Heart failure (HF) presents a massive burden to health care with a complex pathophysiology that results in HF with reduced left ventricle ejection fraction (EF) or HF with preserved EF. It has been shown that relatively modest changes in protein glycosylation, an essential posttranslational modification, are associated with clinical presentations of HF. We and others previously showed that such aberrant protein glycosylation in animal models can lead to HF. Methods and Results We develop and characterize a novel, tamoxifen‐inducible, cardiomyocyte Mgat1 knockout mouse strain, achieved through deletion of Mgat1, alpha‐1,3‐mannosyl‐glycoproten 2‐beta‐N‐acetlyglucosaminyltransferase, which encodes N‐acetylglucosaminyltransferase I. We investigate the role of hybrid/complex N‐glycosylation in adult HFrEF pathogenesis at the ion channel, cardiomyocyte, tissue, and gross cardiac level. The data demonstrate successful reduction of N‐acetylglucosaminyltransferase I activity and confirm that hybrid/complex N‐glycans modulate gating of cardiomyocyte voltage‐gated calcium channels. A longitudinal study shows that the tamoxifen‐inducible, cardiomyocyte Mgat1 knockout mice present with significantly reduced systolic function by 28 days post induction that progresses into HFrEF by 8 weeks post induction, without significant ventricular dilation or hypertrophy. Further, there was minimal, if any, physiologic or pathophysiologic cardiomyocyte electromechanical remodeling or fibrosis observed before (10–21 days post induction) or after (90–130 days post induction) HFrEF development. Conclusions The tamoxifen‐inducible, cardiomyocyte Mgat1 knockout mouse strain created and characterized here provides a model to describe novel mechanisms and causes responsible for HFrEF onset in the adult, likely occurring primarily through tissue‐level reductions in electromechanical activity in the absence of (or at least before) cardiomyocyte remodeling and fibrosis.

Abstract Responding to climate impacts and expanding adaptation efforts necessitates getting the right knowledge and tools in the hands of land managers and decision‐makers. In 2022–2023, several regional US Geological Survey Climate Adaptation Science Centers partnered with the US Fish and Wildlife Service (FWS) Science Applications Program on the first targeted climate training series designed for the FWS Grassland Ecosystem Team. This training spanned multiple months and formats with self‐paced virtual lessons, webinars, and an in‐person workshop. As the FWS Grassland Ecosystem Team is tasked with conservation planning for grassland birds and other species, the focus of the workshop was an interactive collaborative activity incorporating species adaptive capacity assessments, future climate projections, and adaptation menus into the decision‐making process. Herein, we describe the methods used to design and deliver the training series, as well as lessons learned for future climate literacy programs aimed at natural resource managers.

Abstract Surf breaks are increasingly recognized as socio‐environmental phenomena that provide opportunities for biodiversity conservation and sustained benefits for local communities. Here, we examine an additional benefit from improved conservation of the ecosystems that host and surround surf breaks—their coincidence with carbon dense coastal ecosystems. Using global spatial datasets of irrecoverable carbon (defined as carbon stocks that, if lost today, could not be recovered within 30 years' time), surf break locations, ecosystem types, protected areas, and Key Biodiversity Areas, we identified 88.3 million tonnes of irrecoverable carbon held in surf ecosystems. Of this total, 17.2 million tonnes are found in Key Biodiversity Areas without formal measures of protection. These results highlight surf conservation as a potential avenue to simultaneously mitigate climate change, protect biodiversity, and promote sustainable development in coastal communities.

Abstract The success of avian translocations depends on many factors. Release age is often cited as an influential factor that warrants further study, yet no general guidelines exist to improve the outcome of translocations. We conducted a systematic review of literature on captive‐reared or wild‐caught birds that incorporated >1 age class in their analyses of post‐release survival, dispersal, or reproduction. Fifty‐two studies met our search criteria, and 39 were retained for an evaluation of post‐release survival. For studies reporting at least one trend, more reported higher post‐release survival when birds were translocated at younger ages (68%) than at older ages (32%). This pattern was most pronounced for wild‐caught birds and for captive‐reared birds released within their first year of life. Captive‐reared birds of prey were an exception, with birds released at older ages often having higher survival than birds released at younger ages. We review the authors' hypotheses for why birds released at younger ages are more likely to settle, survive, and breed. More research is needed on the potential effects of release age on dispersal and reproduction. We recommend that future studies incorporate age of release as a covariate and control for the effect of season of release in experiments.

Abstract Wood ducks (Aix sponsa) are secondary natural cavity‐nesting species that also nest in artificial nest boxes. Since the early 20th century, nest boxes have been widely deployed in North America to increase nesting sites for wood ducks and bolster production. Equipping nest boxes with a predator guard beneath the box is a common practice to deter climbing predators from accessing boxes; however, there is no device to repel avian predators. We found that eastern rat snakes (Pantherophis alleghaniensis) and woodpeckers (Picidae) were primary predators of wood duck eggs in boxes in North Carolina and South Carolina. Accordingly, we designed experiments to deter snakes and woodpeckers using a commercial brand of snake repellent pellets and a plastic raptor decoy, respectively. Male and female snakes that accessed boxes averaged 1.4 m (SE = 2.0 cm) in length. Digital camera data indicated that snakes climbed nest box posts and thrust their anterior body atop predator guards to continue their ascent into the box. We recorded 671 nest failures of which rat snakes accounted for 39.9% (n = 268) and woodpeckers 22.4% (n = 150). Snakes consumed ≥649 eggs, observed as protuberances in their stomachs. Our experiment showed that commercial snake repellent pellets did not deter snakes (P = 0.957). Placing a plastic hawk decoy atop nest boxes when females were incubating ≥12 days increased nest survival during the incubation stage (P = 0.001). Wood duck nest boxes at our study sites may be experiencing increased nest predation by rat snakes due to poor maintenance and installation of predator guards. Rat snakes and woodpeckers may be depredating wood duck eggs in the southeastern United States at unknown rates, potentially decreasing production and recruitment from these structures.

Abstract Background The COVID‐19 pandemic, caused by the SARS‐CoV‐2 virus, has resulted in illness, deaths and societal disruption on a global scale. Societies have implemented various control measures to reduce transmission of the virus and mitigate its impact. Individual behavioural changes are crucial to the successful implementation of these measures. One commonly recommended measure to limit risk of infection is frequent handwashing. It is important to identify those factors that can predict the uptake and maintenance of handwashing. Objectives We aimed to identify and synthesise the evidence on malleable psychological and psychosocial factors that determine uptake and adherence to handwashing aimed at reducing the risk of infection or transmission of COVID‐19. Search Methods We searched various literature sources including electronic databases (Medline ALL, Child Development & Adolescent Studies, ERIC, PsycInfo, CINAHL and Web of Science), web searches, conference proceedings, government reports, other repositories of literature and grey literature. The search strategy was built around three concepts of interest including (1) context (terms relating to COVID‐19), (2) behaviour of interest and (3) terms related to psychological and psychosocial determinants of COVID Health‐Related Behaviours and adherence or compliance with handwashing, to capture malleable determines. Searches capture studies up until October 2021. Selection Criteria Eligibility criteria included observational studies (both retrospective and prospective) and experimental studies that measure and report malleable psychological and psychosocial determinants and handwashing at an individual level, amongst the general public. Screening was supported by the Cochrane Crowd. Titles and abstracts were screened against the eligibility criteria by three independent screeners. Following this, all potentially relevant studies were screened at full‐text level by the research team. All conflicts between screeners were resolved by discussion between the core research team. Data Collection and Analysis All data extraction was managed in EPPI‐Reviewer software. All eligible studies, identified through full‐text screening were extracted by one author. We extracted data on study information, population, determinant, behaviour and effects. A second author checked data extraction on 20% of all included papers. All conflicts were discussed by the two authors until consensus was reached. We assessed methodological quality of all included studies using an adapted version of the Joanna Briggs Institute Quality appraisal tool for cross‐sectional studies. Main Results Our initial searches yielded 23,587 results, of which 56 studies were included in this review. The included studies were cross sectional in design, came from 22 countries and had a combined sample of 199,376 participants. The vast majority of studies had samples from the general public, with eight of the studies focusing on specific samples. All included studies considered people over the age of 18. The quality of the majority of the studies was good (n = 30 rated low risk of bias), with 8 rated high risk of bias, predominately due to lack of reporting of recruitment, sample characteristics and methodology. Thirty‐four studies were included in the narrative synthesis and 28 in the meta‐analysis. Findings indicated that emotions about COVID‐19 (worry [0.381, confidence interval [CI] = 0.270–0.482, I2 = 92%) and anxiety (0.308, CI = 0.154–0.448, I2 = 91%]), knowledge of COVID‐19 (0.323, CI = 0.223–0.417, I2 = 94%), and perceived social norms (0.303, CI = 0.184–0.413, I2 = 92%) were among the malleable determinants most associated with handwashing. Perceived severity (0.006, CI = ‐0.011–0.023) and susceptibility of COVID‐19 (0.041, CI = −0.034 to 0.115) had little to no effect on handwashing behaviour. Authors' Conclusions Understanding the effects of various malleable determinants on COVID‐related handwashing can aid in the development and implementation of interventions and public health campaigns to promote handwashing behaviour in potential new waves of COVID‐19 or other respiratory infections. Emotions about COVID, knowledge of COVID and perceived social norms warrant further consideration in future research and policy.

Abstract Background The COVID‐19 pandemic, caused by the SARS‐CoV‐2 virus, has resulted in illness, deaths and societal disruption on a global scale. Societies have implemented various control measures to reduce transmission of the virus and mitigate its impact. Individual behavioural changes are crucial to the successful implementation of these measures. One commonly recommended measure to limit risk of infection is face covering. It is important to identify those factors that can predict the uptake and maintenance of face covering. Objectives We aimed to identify and synthesise the evidence on malleable psychological and psychosocial factors that determine uptake and adherence to face covering aimed at reducing the risk of infection or transmission of COVID‐19. Search Methods We searched various literature sources including electronic databases (Medline ALL, Child Development & Adolescent Studies, ERIC, PsycInfo, CINAHL & Web of Science), web searches, conference proceedings, government reports, other repositories of literature and grey literature. The search strategy was built around three concepts of interest including (1) context (terms relating to COVID19), (2) behaviour of interest and (3) terms related to psychological and psychosocial determinants of COVID Health‐Related Behaviours and adherence or compliance with face covering, to capture malleable determines. Searches capture studies up until October 2021. Selection Criteria Eligibility criteria included observational studies (both retrospective and prospective) and experimental studies that measure and report malleable psychological and psychosocial determinants and handwashing at an individual level, amongst the general public. Screening was supported by the Cochrane Crowd. Studies titles and abstracts were screened against the eligibility criteria by three independent screeners. Following this, all potentially relevant studies were screened at full‐text level by the research team. All conflicts between screeners were resolved by discussion between the core research team. Data Collection and Analysis All data extraction was managed in EPPI‐Reviewer software. All eligible studies, identified through full‐text screening were extracted by one author. We extracted data on study information, population, determinant, behaviour and effects. A second author checked data extraction on 20% of all included papers. All conflicts were discussed by the two authors until consensus was reached. We assessed methodological quality of all included studies using an adapted version of the Joanna Briggs Institute Quality appraisal tool for cross‐sectional studies. Main Results Our initial searches yielded 23,587 results, of which 23 were included in this review. The included studies were cross‐sectional in design, came from nine countries and had a combined sample of 54,401 participants. The vast majority of studies had samples from the general public, with five of the studies focusing on specific samples. All included studies considered people over the age of 18. The quality of 10 of the studies was rated as unclear, 10 were rated as low, and 3 rated high risk of bias, predominately due to lack of reporting of recruitment, sample characteristics and methodology. Ten studies were included in the meta‐analysis and 16 in the narrative synthesis. Findings from the meta‐analysis indicated that knowledge of COVID‐19 (0.341, 95% confidence interval [CI] = 0.06, 0.530, I2 = 100%) was the malleable determinant most associated with face covering behaviour. Perceived susceptibility of COVID‐19 (r = 0.088, 95% CI = −0.004, 0.180, I2 = 80%) and COVID‐related worry and anxiety (r = 0.064, 95% CI = −0.066, 0.191, I2 = 93% had little to no effect on face covering behaviour. In the narrative synthesis, the strongest association was found between perceived benefits and effectiveness of behaviours and mask wearing behaviour. Authors' Conclusions Understanding the effects of various malleable determinants on COVID‐related face covering can aid in the development and implementation of interventions and public health campaigns to promote face covering behaviour in potential new waves of COVID‐19 or other respiratory infections. Knowledge of COVID and perceived benefits of face coverings warrant further consideration in future research and policy.

Abstract The aim of this scoping review was to synthesize published studies and ongoing clinical trials of psychological interventions for mental health problems associated with COVID‐19 infection. The study protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) Extension for Scoping Reviews. We conducted systematic searches for studies published or registered between January 2020 and October 2022 using eight scientific databases and clinical trial registries, which identified 40 complete published studies and 53 ongoing clinical trials. We found that most studies were randomized controlled trials (74%) while the remaining used study designs of lower methodological quality. Most studies investigated interventions for acute COVID‐19 patients (74%) and others explored post‐COVID conditions (PCC) or recovered patients. Cognitive and behavioral therapies were the main intervention approaches (31%), followed by multidisciplinary programs (21%) and mindfulness (17%). The most frequently evaluated outcomes were anxiety (33%), depression (26%), quality of life (13%), and insomnia (10%). No studies on youths, older people, or marginalized communities were found. These findings summarize the burgeoning research on a range of psychological interventions for individuals infected with COVID‐19. However, the field is in its infancy and further research to develop an evidence base for targeted care is necessary. The gaps identified in the current study also highlight the need for more research on youths, older people, and members of marginalized communities, and PCC patients. It is important to ascertain interventions and delivery strategies that are not only effective and affordable but also allow high scalability and accessibility.

Abstract Our solar system's path has recently been shown to potentially intersect dense interstellar clouds 2 and 7 million years ago: the Local Lynx of Cold Cloud and the edge of the Local Bubble. These clouds compressed the heliosphere, directly exposing Earth to the interstellar medium. Previous studies that examined climate effects of these encounters argued for an induced ice age due to the formation of global noctilucent clouds (NLCs). Here, we revisit such studies with a modern 2D atmospheric chemistry model using parameters of global heliospheric magnetohydrodynamic models as input. We show that NLCs remain confined to polar latitudes and short seasonal lifetimes during these dense cloud crossings lasting ∼105 years. Polar mesospheric ozone becomes significantly depleted, but the total ozone column broadly increases. Furthermore, we show that the densest NLCs lessen the amount of sunlight reaching the surface instantaneously by up to 7% while halving outgoing longwave radiation.

Abstract INTRODUCTION Alzheimer's disease (AD) neuropathological changes present with amnestic and nonamnestic (atypical) syndromes. The contribution of comorbid neuropathology as a substratum of atypical expression of AD remains under investigated. METHODS We examined whether atypical AD exhibited increased comorbid neuropathology compared to typical AD and if such neuropathologies contributed to the accelerated clinical decline in atypical AD. RESULTS We examined 60 atypical and 101 typical AD clinicopathological cases. The number of comorbid pathologies was similar between the groups (p = 0.09). Argyrophilic grain disease was associated with atypical presentation (p = 0.008) after accounting for sex, age of onset, and disease duration. Vascular brain injury was more common in typical AD (p = 0.022). Atypical cases had a steeper Mini‐Mental Status Examination (MMSE) decline over time (p = 0.033). DISCUSSION Comorbid neuropathological changes are unlikely to contribute to atypical AD presentation and the steeper cognitive decline seen in this cohort. Highlights Autopsy cohort of 60 atypical and 101 typical AD; does comorbid pathology explain atypical presentation? Atypical versus Typical AD: No significant differences in comorbid neuropathologies were found (p = 0.09). Argyrophilic Grain Disease Association: significantly correlates with atypical AD presentations, suggesting a unique neuropathological pattern (p = 0.008). Vascular Brain Injury Prevalence: Vascular brain injury is more common in typical AD than in atypical AD (p = 0.022). Cognitive Decline in Atypical AD: Atypical AD patients experience a steeper cognitive decline measured by MMSE than those with typical AD despite lacking more comorbid neuropathology, highlighting the severity of atypical AD pathogenesis (p = 0.033).

Abstract The southeastern United States Coastal Plain ecosystem contains baldcypress (Taxodium distichum) swamps and grass‐dominated marshes. These ecosystems also occurred on the exposed continental shelf during lower sea levels but are rarely preserved due to the mechanically erosive nature of transgression and regression. Two presently marine sites on the northeastern Gulf of Mexico's continental shelf contain well‐preserved woody terrestrial sediments that were the subject of previous studies. This study continues the investigation using geochemical (δ13C, δ15N, δ34S) and palynological characteristics of these formerly terrestrial sediments to determine if swamps and/or marshes existed at the time of deposition. The first site is located ∼20 km southeast of Horn Island, Mississippi (MS) and the core has terrestrial sediments radiocarbon dated to 11,066–10,228 (2σ) calibrated years BP (early Holocene). The second site is the “Alabama Underwater Forest” located ∼13 km south of Gulf Shores, Alabama (AL) and the cores have terrestrial sediments optically stimulated luminescence dated to 63 ka (±10 ka, 2σ) to 72 ka (±16 ka, 2σ) (late Pleistocene). Geochemical results for the MS sediments indicate a swamp‐to‐freshwater marsh transitional series, whereas the AL sediments indicate a swamp‐to‐saltwater marsh transitional series, both supported by palynological results. Further exploration of the geochemical results using linear discriminant analysis, trained with published geochemical data, supports the swamp and marsh interpretations. We conclude that the near‐pristine preservation of these woody deposits is not solely due to physical mechanisms, such as rapid burial, but is also coupled with anoxia‐ and euxinia‐driven biogeochemical reactions promoting wood and woody debris preservation in swamp and marsh environments.

Abstract Eye movement desensitisation and reprocessing (EMDR) therapy is a transdiagnostic, comprehensive, integrative, evidence‐based treatment intervention for post‐traumatic stress disorder (PTSD), complex PTSD, and perinatal PTSD. PTSD can arise from an experience of pregnancy or birth related trauma. Despite this, there is limited availability and access to EMDR therapy within the United Kingdom National Health Service. EMDR is a psychotherapeutic intervention which is usually delivered by highly specialist mental health professionals. However, with such a robust protocol, it is appropriate to consider if other health professionals should be trained to deliver EMDR. Humanitarian trauma capacity‐building projects in a global context have shown that task shifting can assist with addressing unmet mental health therapy needs. Midwives are highly skilled graduates working in the perinatal period who understand that women's emotional health is as important as their physical health. Therefore, it was proposed that EMDR knowledge and skills could be efficiently task shifted to midwives. The aim and objectives were to train midwives to deliver modified EMDR scripted protocols and techniques and explore qualitative and quantitative outcomes of a bespoke EMDR for midwives (EMDR‐m) educational programme. The online training was delivered to the midwives over 4 days with clinical practicums incorporated throughout. Pre and post‐tests demonstrated an increase in their EMDR knowledge, skills and confidence. EMDR Group Supervision provided by three experienced EMDR Accredited Practitioners was mandatory for 6 weeks post‐training and ongoing one‐to‐one supervision was made available. Midwives scored the course 9.6/10 (range 8–10) and described it as ‘amazing’ and ‘invaluable’. Challenges for the future include ring‐fenced time and an appropriate space to deliver the therapy. Those midwives who completed the training have progressed to deliver early EMDR‐m interventions in a perinatal mental health research study in their own Health and Social Care Trust (reported elsewhere).

Abstract Background In 2020, a novel neurologic disease was observed in juvenile Quarter Horses (QHs) in North America. It was unknown if this was an aberrant manifestation of another previously described neurological disorder in foals, such as equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM). Hypothesis/Objectives To describe the clinical findings, outcomes, and postmortem changes with Equine Juvenile Spinocerebellar Ataxia (EJSCA), differentiate the disease from other similar neurological disorders, and determine a mode of inheritance. Animals Twelve neurologically affected QH foals and the dams. Methods Genomic DNA was isolated and pedigrees were manually constructed. Results All foals (n = 12/12) had a history of acute onset of neurological deficits with no history of trauma. Neurological deficits were characterized by asymmetrical spinal ataxia, with pelvic limbs more severely affected than thoracic limbs. Clinicopathological abnormalities included high serum activity of gamma‐glutamyl transferase and hyperglycemia. All foals became recumbent (median, 3 days: [0–18 days]), which necessitated humane euthanasia (n = 11/12, 92%; the remaining case was found dead). Histological evaluation at postmortem revealed dilated myelin sheaths and digestion chambers within the spinal cord, most prominently in the dorsal spinocerebellar tracts. Pedigree analysis revealed a likely autosomal recessive mode of inheritance. Conclusions and Clinical Importance EJSCA is a uniformly fatal, rapidly progressive, likely autosomal recessive neurological disease of QHs

Abstract The use of head‐mounted augmented reality (AR) for surgeries has grown rapidly in recent years. AR aids in intraoperative surgical navigation through overlaying three‐dimensional (3D) holographic reconstructions of medical data. However, performing AR surgeries on complex areas such as the head and neck region poses challenges in terms of accuracy and speed. This study explores the feasibility of an AR guidance system for resections of positive tumour margins in a cadaveric specimen. The authors present an intraoperative solution that enables surgeons to upload and visualize holographic reconstructions of resected cadaver tissues. The solution involves using a 3D scanner to capture detailed scans of the resected tissue, which are subsequently uploaded into our software. The software converts the scans of resected tissues into specimen holograms that are viewable through a head‐mounted AR display. By re‐aligning these holograms with cadavers with gestures or voice commands, surgeons can navigate the head and neck tumour site. This workflow can run concurrently with frozen section analysis. On average, the authors achieve an uploading time of 2.98 min, visualization time of 1.05 min, and re‐alignment time of 4.39 min, compared to the 20 to 30 min typical for frozen section analysis. The authors achieve a mean re‐alignment error of 3.1 mm. The authors’ software provides a foundation for new research and product development for using AR to navigate complex 3D anatomy in surgery.

Abstract Aims Population‐wide, person‐level, linked electronic health record data are increasingly used to estimate epidemiology, guide resource allocation, and identify events in clinical trials. The accuracy of data from NHS Digital (now part of NHS England) for identifying hospitalization for heart failure (HHF), a key HF standard, is not clear. This study aimed to evaluate the accuracy of NHS Digital data for identifying HHF. Methods and results Patients experiencing at least one HHF, as determined by NHS Digital data, and age‐ and sex‐matched patients not experiencing HHF, were identified from a prospective cohort study and underwent expert adjudication. Three code sets commonly used to identify HHF were applied to the data and compared with expert adjudication (I50: International Classification of Diseases‐10 codes beginning I50; OIS: Clinical Commissioning Groups Outcomes Indicator Set; and NICOR: National Institute for Cardiovascular Outcomes Research, used as the basis for the National Heart Failure Audit in England and Wales). Five hundred four patients underwent expert adjudication, of which 10 (2%) were adjudicated to have experienced HHF. Specificity was high across all three code sets in the first diagnosis position {I50: 96.2% [95% confidence interval (CI) 94.1–97.7%]; NICOR: 93.3% [CI 90.8–95.4%]; OIS: 95.6% [CI 93.3–97.2%]} but decreased substantially as the number of diagnosis positions expanded. Sensitivity [40.0% (CI 12.2–73.8%)] and positive predictive value (PPV) [highest with I50: 17.4% (CI 8.1–33.6%)] were low in the first diagnosis position for all coding sets. PPV was higher for the National Heart Failure Audit criteria, albeit modestly [36.4% (CI 16.6–62.2%)]. Conclusions NHS Digital data were not able to accurately identify HHF and should not be used in isolation for this purpose.

Abstract For the past few years, the addition of renewable energy sources has been on the rise, but the unregulated addition of these sources can cause severe harm to the grid. Therefore, it is necessary to have a predefined limit for a grid, beyond which no further addition of renewables should be allowed without reinforcement. That limit is called the hosting capacity (HC), which is addressed in the literature by search‐based methods with heavy computational burdens. This manuscript first presents a framework to find the HC for a grid. The same framework is then applied to 503 different simulated but realistic LV distribution feeders in Finland to find their HCs and the most effective network parameters in defining a network specific HC. Next, different machine learning models, that is, Decision Tree (DT), Random Forest (RF), Linear Regression (LR), K nearest neighbours (KNN), Logistic Regression, and Support Vector Machine (SVM) are implemented on the generated data. For the classification case, the accuracy values for logistic regression, KNN, and SVM were 0.89, 0.84, and 0.81, respectively. The findings demonstrate that the developed machine learning based technique will enable distribution network operators in finding the HC without applying any deterministic or probabilistic approaches.

Abstract Closely related sexual and parthenogenetic species often show distinct distribution patterns, known as geographical parthenogenesis. Similar patterns, characterized by the existence of separate sexual and parthenogenetic populations across their natural range, can also be found in facultative parthenogens – species in which every female is capable of both sexual and parthenogenetic reproduction. The underlying mechanisms driving this phenomenon in nature remain unclear. Features of the habitat, such as differences in host‐plant phenotypes or niche breadth, could favour sexual or asexual reproductive modes and thus help to explain geographical parthenogenesis in natural insect populations. Megacrania batesii is a facultatively parthenogenetic stick insect that displays geographical parthenogenesis in the wild. We aimed to explore whether sexual and parthenogenetic populations of M. batesii displayed niche differentiation or variations in niche breadth that could explain the separation of the two population types. To do this, we sampled host plants from across the range of M. batesii and quantified phenotypic traits that might affect palatability or accessibility for M. batesii, including leaf thickness, toughness, spike size and density, plant height, and chemical composition. We also quantified host‐plant density, which could affect M. batesii dispersal. We found little evidence of phenotypic differences between host plants supporting sexual versus asexual M. batesii populations, and no difference in host‐plant density or niche breadth between the two population types. Our results suggest that habitat parameters do not play a substantial role in shaping patterns of geographical parthenogenesis in wild populations of M. batesii. Instead, population sex ratio variation could result from interactions between the sexes or dispersal dynamics.

Abstract The atmospheric CO2 growth rate is a fundamental measure of climate forcing. NOAA's growth rate estimates, derived from in situ observations at the marine boundary layer (MBL), serve as the benchmark in policy and science. However, NOAA's MBL‐based method encounters challenges in accurately estimating the whole‐atmosphere CO2 growth rate at sub‐annual scales. Here we introduce the Growth Rate from Satellite Observations (GRESO) method as a complementary approach to estimate the whole‐atmosphere CO2 growth rate utilizing satellite data. Satellite CO2 observations offer extensive atmospheric coverage that extends the capability of the current NOAA benchmark. We assess the sampling errors of the GRESO and NOAA methods using 10 atmospheric transport model simulations. The simulations generate synthetic OCO‐2 satellite and NOAA MBL data for calculating CO2 growth rates, which are compared against the global sum of carbon fluxes used as model inputs. We find good performance for the NOAA method (R = 0.93, RMSE = 0.12 ppm year−1 or 0.25 PgC year−1). GRESO demonstrates lower sampling errors (R = 1.00; RMSE = 0.04 ppm year−1 or 0.09 PgC year−1). Additionally, GRESO shows better performance at monthly scales than the NOAA method (R = 0.76 vs. 0.47, respectively). Due to CO2's atmospheric longevity, the NOAA method accurately captures growth rates over 5‐year intervals. GRESO's robustness across partial coverage configurations (ocean or land data) shows that satellites can be promising tools for low‐latency CO2 growth rate information, provided the systematic biases are minimized using in situ observations. Along with accurate and calibrated NOAA in situ data, satellite‐derived growth rates can provide information about the global carbon cycle at sub‐annual scales.

Abstract Emergency department (ED) overcrowding remains a persistent challenge in global public health, leading to detrimental outcomes for patients and healthcare professionals. Traditional approaches to improve this issue have been insufficient, prompting exploration of novel strategies such as virtual care interventions. Our team developed the first comprehensive statewide virtual ED in Australia, the Victorian Virtual Emergency Department, offering an alternative to in‐person care for non‐life‐threatening emergencies. Here, we present the development and ongoing refinement of this pioneering virtual care service, aiming to provide insights for hospital administrators and policymakers seeking to implement patient‐centric care solutions worldwide. By sharing our model of care, we hope to guide further work toward addressing the global problem of over crowded EDs.

Abstract Background The optimal treatment approach for low‐risk prostate cancer (LRPC) remains controversial. While active surveillance is an increasingly popular option, definitive local treatments, including radical prostatectomy (RP), external beam radiotherapy (EBRT), and prostate seed implantation (PSI), are also commonly used. This study aimed to evaluate the survival outcomes of patients with LRPC using a large patient population from the National Cancer Database (NCDB). Methods We analyzed data from 195,452 patients diagnosed with LRPC between 2004 and 2015 using the NCDB. Patients were classified based on their treatment modalities, including RP, EBRT, PSI, or no local treatment (NLT). Only patients with Charlson–Deyo comorbidity scores of 0 or 1 were included to ensure comparability. Propensity score analysis was used to balance the treatment groups, and the accelerated failure time model was used to analyze the survival rates of the treatment groups. Results After a median follow‐up of 70.8 months, 24,545 deaths occurred, resulting in an all‐cause mortality rate of 13%. RP demonstrated a survival benefit compared with NLT, particularly in patients younger than 74 years of age. In contrast, radiation treatments (EBRT and PSI) did not improve survival in the younger age groups, except for patients older than 70 years for EBRT and older than 65 years for PSI. Notably, EBRT in patients younger than 65 years was associated with inferior outcomes. Conclusion This study highlights the differences in survival outcomes among LRPC treatment modalities. RP was associated with improved survival compared to NLT, especially in younger patients. In contrast, EBRT and PSI showed survival benefits primarily in the older age groups. NLT is a reasonable choice, particularly in younger patients when RP is not chosen. These findings emphasize the importance of individualized treatment decisions for LRPC management.

Abstract Introduction Basal cell carcinoma (BCC) is the most common malignancy in the United States. The majority of cases are identified in Non‐Hispanic Whites (NHW) and are far less demonstrated in patients of colour (POC). However, the Hispanic population represents a large and growing proportion of the US population, and skin cancer diagnoses in Hispanics are rising. Thus, the goal of this study is to examine clinicopathologic differences between BCC in Hispanics versus NHW. Methods A retrospective chart review of Hispanic and NHW patients with BCC at Los Angeles County + USC Medical Center from January 2018 to March 2020 was performed. In total, 101 BCC samples from the first 100 patients identified of Hispanic ancestry, as well as 50 BCC samples identified from the first 50 patients identifying as NHW, were included for analysis. Patient characteristics (age, sex, medical history, and ethnicity), as well as tumour characteristics (location, subtype, tumour depth, and perineural invasion), were collected. We used between subjects t‐tests for continuous variables, and chi‐square tests for categorical variables. Results In total, 151 specimens were collected amongst 122 subjects (79 Hispanics and 43 NHW patients). Among NHW, the majority of patients (74.4%) were men, but among the Hispanic population, the majority (68.4%) were female (p

Abstract Lions (Panthera leo) are declining across their range, mainly due to human‐induced habitat fragmentation and prey depletion. However, the South African lion population continues to grow. Unlike other range states, South Africa actively manages wild lions across a continuum of landscapes and ecological constraints. Many of these lions are in small, fenced reserves where managers seek to mimic ecological processes in small landscapes. However, the effectiveness of this management approach has not been evaluated against meta‐population criteria. Given that meta‐population dynamics allows species living in fragmented habitats to persist, we evaluated how South Africa's lion population complies with meta‐population criteria using national audit data between 2010 and 2019 from 49 fenced, wild lion reserves. The small, fenced reserves holding wild lions fulfil the criteria for meta‐population functionality. However, this functionality was achieved through haphazard and uncoordinated management actions and not through a coordinated approach. Our main recommendation is to consider implementing a more coordinated meta‐population management approach. At the very least, meta‐population management guidelines should be reviewed and updated on a regular basis, regular audits should be conducted and periodic genetic evaluation of the meta‐population (every 10 years) should be instituted. We recommend incentivising lion managers to enhance the conservation of lions in South Africa within a meta‐population framework. We also recommend a focus on improving decision making and policy procedures that facilitates compliance with relevant legislation aimed at achieving high levels of lion conservation‐governance efficiency. South Africa's meta‐population approach to wild lion management in small, fenced reserves is effective at conserving lions and contributing to lion conservation more broadly. In an increasingly fragmented landscape, the need for human management actions to ensure persistence of large carnivores is likely to increase. A managed meta‐population approach of fenced (or unfenced, but geographically isolated) populations is a useful tool for conservationists to consider worldwide.

Abstract Purpose Septic arthritis of any joint is an orthopaedic emergency which requires prompt diagnosis and treatment. The knee is the commonest joint afflicted, and the primary objective of any treatment is complete source control. This commonly takes the form of antibiotic therapy and a washout of the infected joint by means of arthroscopy or arthrotomy. The primary aim of this review is to investigate if arthroscopic washout for native knee septic arthritis confers a lower risk of repeat procedure than arthrotomy. Methods A systematic review and meta‐analysis was conducted of the MEDLINE, SCOPUS and the Cochrane Library data bases. The primary outcome of interest was requirement for repeat washout with all‐cause complications, length of inpatient stay and mortality secondary outcomes. Results A total of 17,140 subjects were included for analysis of the primary outcome, and the overall rate of repeat procedure was 14.6%. No statistical difference was found between arthroscopy and arthrotomy for repeat washout (risk ratio 0.86 [95% confidence interval, CI: 0.72–1.02], I2 = 36%). Eligible studies found in favour of arthroscopy for all‐cause complication rate (risk ratio 0.75 [95% CI: 0.6–0.93], I2 = 84%) and length of stay in hospital (mean difference −1.98 days [95% CI: −3.43 to −0.53], I2 = 84%). No statistical difference was found for the mortality rate (risk ratio 1.17 [95% CI: 0.52–2.63], I2 = 57%). Conclusion Our analysis found arthroscopy and open arthrotomy to be equivocal for repeat surgical washout in native knee septic arthritis. All‐cause complication rate and length of inpatient stay were favourable for arthroscopy with no difference noted between mortality rates. Level of Evidence Level III.

Abstract Molecular detection of environmental DNA (eDNA) and RNA (eRNA) allows highly sensitive qualitative (i.e., presence or absence) and quantitative (i.e., abundance) monitoring of aquatic bacteria. However, bacterial molecular diagnostics are limited by low positive predictive values. Protocols for bacterial eDNA and eRNA molecular monitoring have primarily focused on optimizing specimen collection, and the optimal method to purify bacterial nucleic material from postcollection aquatic specimens to maximize the analytical sensitivity of molecular diagnostics remains poorly defined. Accordingly, strategies to isolate bacterial eDNA and eRNA from fresh and saltwater were investigated. We evaluated two filtration and four nucleic acid purification systems as representative of current generation bacterial eDNA and eRNA isolation strategies for capacity to isolate bacterial eDNA and eRNA from prelysed (i.e., free‐nucleic acids) and viable (i.e., colony forming units, CFU) bacterial cells. We also compared the sensitivities of reverse transcription quantitative PCR (RT‐qPCR) and metagenomic shotgun microbiome sequencing. The optimal protocol used 0.7 μm borosilicate glass filters (Whatman plc) followed by extraction with the RNeasy PowerWater kit (Qiagen). The protocol had a very high analytical sensitivity (10−3–100 ng and 102–101 CFU detected in 500 mL) across multiple species of bacteria, when tested with either RTqPCR or metagenomic sequencing. Importantly, this study highlighted several limitations which are restrictive to both qualitative and quantitative bacterial eDNA and eRNA studies. First, a 12‐h time course between sampling and extraction revealed significant species‐specific changes in cell number and free‐nucleic acid concentrations can occur postspecimen collection. Second, we found Gram‐positive bacteria yielded less nucleic material compared to Gram‐negative bacteria suggesting bacterial eDNA and eRNA studies could be biased by microorganism genome stability and extraction efficiency. This study highlights the need to define the species‐specific diagnostic sensitivity of a protocol when monitoring aquatic bacterial eDNA and eRNA with molecular diagnostics.

Key Clinical Message This case report presents a progressively declining 17‐year‐old patient with membrane protein‐associated neurodegeneration who demonstrated symptomatic improvements in her dysarthria, dysphagia, and gait, and objective improvements in her 6‐minute walk test and 5 times sit‐to‐stand test during elamipretide treatment.

Background The cholesterol efflux capacity of high density lipoprotein (HDL) is negatively associated with cardiovascular risk. Small HDL particles account almost quantitatively for cholesterol efflux capacity, perhaps mediated through efflux of cholesterol and outer leaflet plasma membrane phospholipids by ABCA1 (ATP binding cassette subfamily A member 1). People with type 1 diabetes are at increased coronary artery disease (CAD) risk despite normal HDL‐cholesterol concentrations. We therefore tested the hypothesis that small HDL particles (HDL‐P)—rather than HDL‐cholesterol—predict incident CAD in type 1 diabetes. Methods and Results Incident CAD (CAD death, myocardial infarction, or coronary revascularization) was determined in 550 individuals with childhood‐onset type 1 diabetes. HDL‐P was quantified by calibrated ion mobility analysis and cholesterol efflux capacity was quantified with validated assays. During a median follow‐up of 26 years, 36.5% of the participants developed incident CAD, for an incidence density of 181.3 per 10 000 person‐years. In multivariable Cox models, neither HDL‐cholesterol nor apolipoprotein A1 concentration was significantly associated with CAD risk. In contrast, higher extra‐small HDL‐P concentrations were significantly associated with decreased CAD risk (hazard ratio [HR], 0.26 [95% CI, 0.14–0.50]). Weaker associations were observed for total HDL‐P (HR, 0.88 [95% CI, 0.83–0.93]), small HDL (HR, 0.83 [95% CI, 0.68–1.02]), medium HDL (HR, 0.79 [95% CI, 0.71–0.89]), and large HDL (HR, 0.72 [95% CI, 0.59–0.89]). Although cholesterol efflux capacity was negatively associated with incident CAD, this association was no longer significant after adjustment for total HDL‐P. Conclusions Lower concentrations of total HDL‐P and HDL subpopulations were positively associated with incident CAD independently of HDL‐cholesterol, apolipoprotein A1, and other common CVD risk factors. Extra‐small HDL was a much stronger predictor of risk than the other HDLs. Our data are consistent with the proposal that extra‐small HDL plays a critical role in cardioprotection in type 1 diabetes, mediated by macrophage cholesterol efflux by the ABCA1 pathway.

Abstract Background Cancer‐related distress (CRD) is widely experienced by people with cancer and is associated with poor outcomes. CRD screening is a recommended practice; however, CRD remains under‐treated due to limited resources targeting unique sources (problems) contributing to CRD. Understanding which sources of CRD are most commonly reported will allow allocation of resources including equipping healthcare providers for intervention. Methods We conducted a systematic review to describe the frequency of patient‐reported sources of CRD and to identify relationships with CRD severity, demographics, and clinical characteristics. We included empirical studies that screened adults with cancer using the NCCN or similar problem list. Most and least common sources of CRD were identified using weighted proportions computed across studies. Relationships between sources of CRD and CRD severity, demographics, and clinical characteristics were summarized narratively. Results Forty‐eight studies were included. The most frequent sources of CRD were worry (55%), fatigue (54%), fears (45%), sadness (44%), pain (41%), and sleep disturbance (40%). Having enough food (0%), substance abuse (3%), childbearing ability (5%), fevers (5%), and spiritual concerns (5%) were infrequently reported. Sources of CRD were related to CRD severity, sex, age, race, marital status, income, education, rurality, treatment type, cancer grade, performance status, and timing of screening. Conclusions Sources of CRD were most frequently emotional and physical, and resources should be targeted to these sources. Relationships between sources of CRD and demographic and clinical variables may suggest profiles of patient subgroups that share similar sources of CRD. Further investigation is necessary to direct intervention development and testing.