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Abstract Objectives To explore the potential impacts of incorporating prebiopsy magnetic resonance imaging into primary care as a triage test within the prostate cancer diagnostic pathway. Subjects and methods Decision analytic modelling with decision trees was utilised for this early economic evaluation. A conceptual model was developed reflecting the common primary care routes to diagnosis for prostate cancer: opportunistic, asymptomatic prostate‐specific antigen (PSA) screening or symptomatic presentation. The use of multiparametric MRI (mpMRI) or biparametric MRI (bpMRI) as a primary care triage test following an elevated PSA result was evaluated. A health system perspective was adopted with a time horizon of 12 months. Health effects were expressed in terms of utilities drawn from the literature. The primary outcome was prostate cancer diagnosis. Evidence used to inform the model was drawn from published primary studies, systematic reviews, and secondary analyses of primary and secondary care datasets. Results Base case analysis showed that the PSA pathway was dominated by both mpMRI‐ and bpMRI‐based pathways for patients undergoing opportunistic screening and symptomatic assessment. bpMRI pathways had greater improvement in cost and utility than mpMRI pathways in both clinical scenarios. Significantly more MRI scans would be performed using the modelled approach (66 626 scans vs. 37 456 scans per 100 000 patients per annum), with fewer subsequent urgent suspected cancer referrals for both mpMRI (38% reduction for screening and symptomatic patients) and bpMRI (72% reduction for screening; 71% for symptomatic) pathways, and a small increase in number of missed cancer diagnoses. Deterministic sensitivity analyses, varying each parameter to its upper and lower 95% confidence intervals, showed no significant change in the dominance of the MRI‐based prostate cancer diagnostic pathways. Conclusion Using prostate MRI as a second‐level triage test for suspected prostate cancer in primary care could reduce health service costs without a detrimental effect on patient utility.

Abstract Background Syndecan‐1 (SDC1) is an established marker of endothelial glycocalyx shedding. Most research on SDC1 has focused on plasma or serum concentrations, and little is known about urine concentrations. Objectives Measure urinary SDC1 concentrations in dogs undergoing anesthesia with either sevoflurane or isoflurane and assess the effects of anesthesia duration and IV crystalloids on urinary SDC1 concentrations. Animals Thirty‐one client‐owned dogs undergoing anesthesia for magnetic resonance imaging (MRI) with or without surgery for suspected intervertebral disk disease (IVDD) were used. Methods Dogs with suspected IVDD were randomized to undergo anesthesia with either sevoflurane or isoflurane. Urine was collected before and immediately after anesthesia for the analysis of SDC1. Urinary creatinine concentrations also were measured, and the ratio of urinary SDC1 to urinary creatinine (USCR) was used to account for dilution. Results Median (range) USCR was significantly higher after anesthesia compared with baseline for all groups combined (P

Abstract Within the Industry 4.0 landscape, humans collaborate with cyber and physical elements to form human‐cyber‐physical systems (HCPS). These environments are increasingly complex and challenging workspaces due to increasing levels of automation and data availability. An effective system design requires suitable frameworks that consider human activities and needs whilst supporting overall system efficacy. Although several reviews of frameworks for technology were identified, none of these focused on the human in the system (moving towards Industry 5). The critical literature review presented provides a summary of HCPS frameworks, maps the considerations for a human in HCPS, and provides insight for future framework and system development. The challenges, recommendations, and areas for further research are discussed.

Background Altered structural brain development has been identified in fetuses with congenital heart disease (CHD), suggesting that the neurodevelopmental impairment observed later in life might originate in utero. There are many interacting factors that may perturb neurodevelopment during the fetal period and manifest as structural brain alterations, such as altered cerebral substrate delivery and aberrant fetal hemodynamics. Methods and Results We extracted structural covariance networks from the log Jacobian determinants of 435 in utero T2 weighted image magnetic resonance imaging scans, (n=67 controls, 368 with CHD) acquired during the third trimester. We fit general linear models to test whether age, sex, expected cerebral substrate delivery, and CHD diagnosis were significant predictors of structural covariance. We identified significant effects of age, sex, cerebral substrate delivery, and specific CHD diagnosis across a variety of structural covariance networks, including primary motor and sensory cortices, cerebellar regions, frontal cortex, extra‐axial cerebrospinal fluid, thalamus, brainstem, and insula, consistent with widespread coordinated aberrant maturation of specific brain regions over the third trimester. Conclusions Structural covariance networks offer a sensitive, data‐driven approach to explore whole‐brain structural changes without anatomical priors. We used them to stratify a heterogenous patient cohort with CHD, highlighting similarities and differences between diagnoses during fetal neurodevelopment. Although there was a clear effect of abnormal fetal hemodynamics on structural brain maturation, our results suggest that this alone does not explain all the variation in brain development between individuals with CHD.

Background Mechanical thrombectomy has changed the landscape of acute ischemic stroke treatment, offering improved outcomes for patients with large vessel occlusions. The interplay between reperfusion techniques and occlusion sites remains a critical consideration in treatment decisions. This study investigates the impact of primary reperfusion techniques—stent retriever classic, stent retriever combination with aspiration, and direct aspiration—on procedural and clinical outcomes at different occlusion sites. Methods Using data from the ASSIST registry, a prospective multinational initiative, patients with anterior circulation acute ischemic stroke with large vessel occlusions (n = 1477) were included. Three primary occlusion sites—M1 segment of the middle cerebral artery, M2 segment of the middle cerebral artery, and the internal carotid artery—were studied. Univariate tests and multivariable logistic regression models were used to assess associations between reperfusion techniques and procedural and clinical outcomes, including the expanded thrombolysis in cerebral infarction score and the modified Rankin Scale, stratified by occlusion site. Results Achieving expanded thrombolysis in cerebral infarction ≥2c after first pass was lower in internal carotid artery occlusions (18.2%, P

Abstract Habitat selection is a critical aspect of a species' ecology, requiring complex decision‐making that is both hierarchical and scale‐dependent, since factors that influence selection may be nested or unequal across scales. Elk (Cervus canadensis) ranged widely across diverse ecoregions in North America prior to European settlement and subsequent eastern extirpation. Most habitat selection studies have occurred within their contemporary western range, even after eastern reintroductions began. As habitat selection can vary by geographic location, available cover, season, and diel period, it is important to understand how a non‐migratory, reintroduced population in northern Wisconsin, USA, is limited by the lack of variation in topography, elevation, and vegetation. We tested scale‐dependent habitat selection on 79 adult elk from 2017 to 2020 using resource selection functions across temporal (i.e., seasonal) and spatial scales (i.e., landscape and home range). We found that selection varied both spatially and temporally, and elk selected areas with the greatest potential to influence fitness at larger scales, meaning elk selected areas closer to escape cover and further from “risky” features (e.g., annual wolf territory centers, county roads, and highways). We found stronger avoidance of annual wolf territory centers during spring, suggesting elk were selecting safer habitats during calving season. Elk selected habitats with less canopy cover across both spatial scales and all seasons, suggesting that elk selected areas with better access to forage as early seral stage stands have greater forage biomass than closed‐canopy forests and direct solar radiation to provide warmth in the cooler seasons. This study provides insight into the complexity of hierarchical decision‐making, such as how risky habitat features and land cover type influence habitat selection differently across seasons and spatial scales, influencing the decision‐making of elk. Scale‐dependent behavior is crucial to understand within specific geographic regions, as these decisions scale up to influence population dynamics.

Abstract Rationale Short‐term weight loss is possible in a variety of settings. However, long‐term, free‐living weight loss maintenance following structured weight loss interventions remains elusive. Objective The purpose was to study body weight trajectories over 2 years of intensive lifestyle intervention (ILI) and up to 4 years of follow‐up versus usual care (UC). Methods Data were obtained from electronic medical records (EMRs) from participating clinics. Baseline (Day 0) was established as the EMR data point closest but prior to the baseline date of the trial. The sample included 111 ILI and 196 UC patients. The primary statistical analysis focused on differentiating weight loss trajectories between ILI and UC. Results The ILI group experienced significantly greater weight loss compared with the UC group from Day 100 to Day 700, beyond which there were no significant differences. Intensive lifestyle intervention patients who maintained ≥5% and ≥10% weight loss at 24 months demonstrated significantly greater weight loss (p

ABSTRACT We are still largely reliant on pesticides for the suppression of arthropod pests which threaten human health and food production, but the recent rise of evolved resistance among important pest species has reduced pesticide efficacy. Despite this, our understanding of strategies that effectively limit the evolution of resistance remains weak. Male‐killing sex ratio distorting microbes (SRDMs), such as Wolbachia and Spiroplasma, are common among arthropod species. Previous theoretical work has suggested that they could limit adaptive potential in two ways: first, because by distorting sex ratios they reduce the effective population size, and second, because infected females produce no male offspring which restricts gene flow. Here we present the results of a novel experiment in which we test the extent by which these two mechanisms limit the adaptive response of arthropods to pesticide. Using a fully factorial design, we manipulated the adult sex ratio of laboratory populations of Drosophila melanogaster, both in the presence and absence of SRDMs, and exposed these populations to six generations of pesticide poisoning. This design allows the effects of SRDMs on sex ratio and their effects on gene flow to be estimated separately. After six generations, individuals from populations with even sex ratios displayed a higher resistance to pesticide relative to individuals from female‐biased populations. By contrast, we found no effect of the presence of SRDMs in host populations on pesticide resistance independent of sex ratio. In addition, males were more susceptible to pesticide than females—this was true of flies from both naïve and previously exposed populations. These findings provide the first empirical proof of concept that sex ratio distortion arising from SRDMs can limit adaptation to pesticides, but cast doubt on the theoretical effect of male‐killers limiting adaptation by disrupting gene flow.

ABSTRACT Background Recurrent squamous cell carcinoma (SCC) of the head and neck (SCCHN) remains a formidable clinical challenge despite available treatments. The phosphatidylinositol 3‐kinase (PI3K) pathway has been identified as a potential therapeutic target, and alpelisib, a selective PI3Kα inhibitor, has demonstrated efficacy in certain malignancies. Combining this targeted therapy with immunotherapy has been suggested in previous studies as a promising strategy to bolster the immune response against cancer. Cases A 69‐year‐old woman with locoregional recurrence of PIK3CA‐mutated SCC of the left maxilla and cervical nodal metastases. Several chemotherapeutic regimens, including cisplatin, docetaxel, 5FU, chemoradiotherapy, and mono‐immunotherapy, resulted in disease progression. Alpelisib combined with pembrolizumab led to a sustained response for 9 months. A 58‐year‐old man with recurrent metastatic PIK3CA‐mutated SCC of the oropharynx, involving the left lung, hilar, and mediastinal lymph nodes. Despite prior palliative radiation and platinum‐based chemotherapy with pembrolizumab and cetuximab, treatment with alpelisib and nivolumab resulted in a partial response. Severe hyperglycemia and rash led to treatment discontinuation. Conclusion Our findings highlight the potential of this innovative therapeutic combination, suggesting a need for further investigations in this setting.

Abstract Background Access to clinical services for children with foot and ankle problems are important, but unravelling the complexity of practice and service delivery can be challenging. The pursuit and implementation of research evidence is critical for driving positive change in practice, but little is understood about the approaches to knowledge and research acquisition in children foot health. Aim The aim of the study was to: (1) explore multi‐professional habits of knowledge and research evidence acquisition in children's foot health; and (2) understand how clinicians integrate information for children and their families into their practice. Methods This was a descriptive, cross‐sectional online survey. Participants were included if they worked in the UK and had experience of working within paediatric services. Results There were complete responses from 247 health professionals, representing physiotherapists (n = 160), podiatrists (n = 50), orthotists (n = 25), nurses and specialists in community public health nurses (health visitors) (n = 12). Three main themes were generated from the data: (1) Factors that influence knowledge and inform clinical practice. (2) The role of Professional Bodies in informing professional knowledge. (3) Health Professionals' views on managing health information for parents and caregivers. Conclusions This work advances understanding of the value health professionals' place in the development of materials for informing professional knowledge, as well as highlighting some of the challenges with translation of knowledge into clinical practice. The findings offer a national perspective of health professionals working on children's foot health and have highlighted that some of the most valued influences on clinical practice come from peer‐to‐peer networking.

Abstract A novel intumescent fire‐retardant coating formulation has been developed by taking advantage of the inherent stability of large cyclic polyphenols (e.g., tannic acid) to remove the need for a dedicated blowing agent, specifically melamine. Cone calorimetry data indicate a lower fire growth rate (FIGRA) (5.0 ± 1.3 vs. 2.4 ± 0.7 kW m−2 s−1) upon removal of melamine. Total smoke release (TSR) increases following this removal (178 ± 21.4 vs. 305 ± 13.2 m2 m−2), which indicates the role of tannic acid in gas generation. Thermogravimetric analysis resulted in similar residue yield from the examined systems (36 ± 1.3% vs. 34 ± 1.7%) despite removal of a dedicated blowing agent. These results indicate that tannic acids multistep degradation allows it to behave as both a char forming and blowing agent in intumescent systems. The observed reduction of acid loading between the melamine‐tannin system and the melamine‐free composition (15.6% vs. 10.6% wt. ammonium polyphosphate, respectively) is also significant. Tannic acid occurs in agricultural waste products, which is encouraging for the pursuit of sustainable chemistry and addressing potential adverse health effects in humans combined with reducing the overall phosphorous loading. Highlights Melamine was removed from the intumescent without compromising stability. The resulting intumescent char was stronger despite less expansion. Tannic acid is attributed as both the charring and blowing agent. The tannin‐based coating requires a lower acid loading for similar performance.

Abstract Neuromodulation via Responsive Neurostimulation (RNS) or Deep Brain Stimulation (DBS) is an emerging treatment strategy for pediatric drug‐resistant epilepsy (DRE). Knowledge gaps exist in patient selection, surgical technique, and perioperative care. Here, we use an expert survey to clarify practices. Thirty‐two members of the Pediatric Epilepsy Research Consortium were surveyed using REDCap. Respondents were from 17 pediatric epilepsy centers (missing data in one): Four centers implant RNS only while 13 implant both RNS and DBS. Thirteen RNS programs commenced in or before 2020, and 10 of 12 DBS programs began thereafter. The busiest six centers implant 6–10 new RNS devices per year; all DBS programs implant 50%) was reported by 81% (13/16) of centers. RNS and DBS are rapidly evolving treatment modalities for safe and effective treatment of pediatric DRE. There is increasing interest in multicenter collaboration to gain knowledge and facilitate dialogue. Plain language summary We surveyed 32 pediatric epilepsy centers in USA to highlight current practices of intracranial neuromodulation. Of the 17 that replied, we found that most centers are implanting thalamic targets in pediatric drug‐resistant epilepsy using the RNS device. DBS device is starting to be used in pediatric epilepsy, especially after 2020. Different strategies for target identification are enumerated. This study serves as a starting point for future collaborative research.

Abstract The adverse outcome pathway (AOP) framework serves as a practical tool for organising scientific knowledge that can be used to infer cause–effect relationships between stressor events and toxicity outcomes in intact organisms. However, a major challenge in the broader application of the AOP concept within regulatory toxicology is the development of a robust AOPs that can withstand peer review and acceptance. This is mainly due to the considerable amount of work required to substantiate the modular units of a complete AOP, which can take years from inception to completion. The methodology used here consisted of an initial assessment of a single chemical hazard using the Integrated Approach to Testing and Assessment (IATA) framework. An evidence‐based approach was then used to gather empirical evidence combining systematic literature review methods with expert knowledge to ensure the effectiveness of the AOP development methodology. The structured framework used assured transparency, objectivity and comprehensiveness, and included expert knowledge elicitation for the evaluation of key event relationships (KERs). This stepwise approach led to the development of an AOP that begins with binding of chemicals to Voltage Gate Sodium Channels (VGSC/Nav) during mammalian development leading to adverse consequences in neurodevelopment evidenced as deficits in cognitive functions. Disruption of the formation of precise neural circuits by alterations in VGSC kinetics during the perinatal stages of brain development may also underlie neurodevelopmental disorders. Gaps in our understanding include the specific critical developmental windows and the quantitative relationship of binding to VGSC and subsequent disruption and cognitive function. Despite the limited quantitative information at all KER levels, regulatory applications of this AOP for DNT assessment have been identified.

Abstract Environmental air pollution presents a considerable risk to global respiratory health. If critical levels are exceeded, inhaled pollutants can lead to the development of respiratory dysfunction and provoke exacerbation in those with pre‐existing chronic respiratory disease. Over 90% of the global population currently reside in areas where environmental air pollution is considered excessive—with adverse effects ranging from acute airway irritation to complex immunomodulatory alterations. This narrative review provides an up‐to‐date perspective concerning the impact of environmental air pollution on respiratory health and function and describes the underpinning mechanisms that contribute to the development and progression of chronic respiratory disease.

ABSTRACT Introduction The impact of multiple health conditions on bowel cancer screening is currently unknown. We explored the impact of multiple health conditions on bowel cancer screening perceptions, experience and clinical management decisions following a positive stool test. Methods Semi‐structured qualitative interviews were conducted remotely with Bowel Screening Wales staff (n = 16) stratified by regional location and role and with screening participants (n = 19) stratified by age, gender and comorbidity. Interview topics were guided by the Common‐Sense Model. Results Screening participants, regardless of comorbidity status, placed great emphasis on the importance of early detection of cancer and completing the bowel screening process. Screening staff emphasised comorbidities in the clinical decision‐making process; however, screening participants had low awareness of the impact that comorbidities can have on bowel screening. Participants describe how the presence of multiple health conditions can mask potential bowel symptoms and influence beliefs about follow‐up. Conclusion Bowel screening staff try to individualise the service to meet participant needs. The potential mismatch in screening staff and participant awareness and expectations of the bowel screening and diagnostic process needs to be addressed. Clearer and more regular communication with screening participants could support the screening process, particularly for those with significant coexisting health conditions or facing time delays. The possible masking effects and misattribution of symptoms because of comorbidities highlight an opportunity for education and raising awareness for screening participants and a potential area of focus for discussions in clinical consultations and staff training. Patient and Public Contribution Project funding included costs for patients and public contributors to be compensated for their contributions to the project, in line with current standards. A patient and public contributor was involved in the design of the study, including protocol development, and the interpretation of key findings and implications for patients, which are subsequently reflected within the manuscript.

Abstract Applications for an antenna structure produced with additive manufacturing technology are numerous and promising. This study focuses explicitly on utilizing micro‐laser sintering (MLS) three‐dimensional (3D) printing technology to fabricate two rectangular horn antennas identical to a standard Pasternack® horn antenna, making the fabrication straightforward. The objective is to investigate how surface roughness affects antenna performance in a frequency range of 18 to 26.5 GHz. One antenna is polished and the other is left untouched, resulting in surface roughness of 4 and 6 µm, respectively, measured using a profilometer. Then, a vector network analyzer was used to assess their reflection coefficient, transmission characteristics, and radiation pattern and determine gains of 8.83 and 9.14 dBi for the polished and unpolished antennas, respectively. The study finds that both polished and unpolished antennas perform similarly, and their characteristics closely resembling simulated and standard antennas. Finally, the performance of the MLS‐printed metallic antennas is compared with horn antennas created using other 3D printing techniques. It reveals that the MLS‐printed metallic structures exhibit better performance, indicating that the MLS technology has great potential to print 3D metallic electromagnetic designs.

Abstract Currently 1677 species are listed under the U.S. Endangered Species Act (ESA), yet only a small percentage have been delisted due to recovery. In the fall of 2021, the U.S. Fish and Wildlife Service proposed delisting 23 species due to extinction. Tracking changes in species ‘recovery status over time is critical to understanding species’ statuses, informing adaptive management strategies, and assessing the performance of the ESA to prevent further species loss. In this paper, we describe four key obstacles in tracking species recovery status under the ESA. First, ESA 5‐year reviews lack a standardized format and clear documentation. Second, despite having been listed for decades, many species still suffer major data gaps in their biology and threats, rendering it difficult if not impossible to track progress towards recovery. Third, many species have continued declining after listing, yet given the above (1 & 2), understanding potential causes (proximate and/or ultimate) can be difficult. Fourth, many species currently have no path to clear recovery, which represents a potential failing of the process. We conclude with a discussion of potential policy responses that could be addressed to enhance the efficacy of the ESA.

Abstract Objective Health care is a significant contributor to the climate crisis. Multidisciplinary clinics (MDC) may reduce carbon emissions by combining multiple appointments into one. This is the first program evaluation study to quantify the carbon footprint associated with multidisciplinary pediatric airway clinics. Study Design Retrospective. Setting Children's Hospital at London Health Sciences Center, London, Canada. Methods Pediatric airway MDC allows patients to see otolaryngology and respirology in one appointment. The carbon and financial savings (Canadian Dollars) of all patients attending the MDC from January 1, 2018 to December 31, 2022 were calculated. Patient postal codes and institutional parking rates were inputted into the CASCADES carbon accounting tool. Total distance was divided into unsustainable (vehicles) and sustainable (transit, walking, cycling) transportation to calculate carbon emissions. Travel costs included cost/kilometer for vehicles (maintenance, license/registration, insurance, fuel) and costs/ride for transit. Results A total of 560 MDC appointments for 300 patients saved 77,785 km. Total carbon emissions saved from travel averted was 16.21 tonnes. The total carbon emissions saved, minus public transit, was 15.60 tonnes. Using the Natural Resources Canada Greenhouse Gas Equivalencies Calculator, 16.21 tonnes are approximately equivalent to 5 passenger vehicles, 6906 L of gasoline, 3.8 homes' energy, and 10.8 homes' electricity use for one year, 36.6 barrels of oil consumed, and 675 propane cylinders. Travel costs of $28,891.83 (no parking), $30,519.40 ($4 minimum parking fee), or $33,774.55 ($12 maximum parking fee) were saved. Conclusion MDC effectively reduced carbon emissions and offered patients financial savings. Similar models can be adapted across institutions to help mitigate climate change.

Abstract Urban environments expose wildlife to levels of anthropogenic noise they would not experience in rural areas (e.g., traffic noise), and research suggests that many species adjust their acoustic signals for optimal transmission in urban soundscapes. However, our understanding of anuran (order Anura) responses to noise pollution in urban environments of the southeastern United States is limited, particularly for species that can breed during winter. Our goal was to examine how vocal anuran advertisement call characteristics during winter varied with increasing distance from roadways in bottomland hardwoods of Louisiana, USA. We deployed acoustic recording units at two sites (i.e., rural and urban) perpendicular to Interstate 10 at 200‐, 400‐, and 600‐m intervals (i.e., close, middle, and far) from November 2019 to January 2020. We detected Cajun Chorus Frogs (Pseudacris fouquettei) and Cricket Frogs (Acris spp.) at our rural site, and only detected Cricket Frogs at our urban site. At the rural site, Cajun Chorus Frogs produced longer duration notes at the far location compared to the middle location. At the urban site, Cricket Frogs produced higher dominant frequency calls at the close location compared to the far and middle locations and longer duration notes at the far location compared to the close location. We were unable to account for additional factors in our models (e.g., temperature, noise levels), but our results generally align with previous research. Our study provides baseline data for future research to examine the potential effects of traffic noise on winter advertisement calls in locations with similar environmental conditions and species.

Abstract Cardiotrophin‐1 (CT‐1), a member of the interleukin (IL)‐6 cytokine family, has renoprotective effects in mouse models of acute kidney disease and tubulointerstitial fibrosis, but its role in glomerular disease is unknown. To address this, we used the mouse model of nephrotoxic nephritis to test the hypothesis that CT‐1 also has a protective role in immune‐mediated glomerular disease. Using immunohistochemistry and analysis of single‐cell RNA‐sequencing data of isolated glomeruli, we demonstrate that CT‐1 is expressed in the glomerulus in male mice, predominantly in parietal epithelial cells and is downregulated in mice with nephrotoxic nephritis. Furthermore, analysis of data from patients revealed that human glomerular disease is also associated with reduced glomerular CT‐1 transcript levels. In male mice with nephrotoxic nephritis and established proteinuria, administration of CT‐1 resulted in reduced albuminuria, prevented podocyte loss, and sustained plasma creatinine, compared with mice administered saline. CT‐1 treatment also reduced fibrosis in the kidney cortex, peri‐glomerular macrophage accumulation and the kidney levels of the pro‐inflammatory mediator complement component 5a. In conclusion, CT‐1 intervention therapy delays the progression of glomerular disease in mice by preserving kidney function and inhibiting renal inflammation and fibrosis.

Abstract Purpose Healthy cancer survivorship involves patients' active engagement with preventative health behaviors and follow‐up care. While clinicians and patients have typically held dual responsibility for activating these behaviors, transitioning some clinician effort to technology and health coaches may enhance guideline implementation. This paper reports on the acceptability of the Shared Healthcare Actions & Reflections Electronic systems in survivorship (SHARE‐S) program, an entirely virtual multicomponent intervention incorporating e‐referrals, remotely‐delivered health coaching, and automated text messages to enhance patient self‐management and promote healthy survivorship. Methods SHARE‐S was evaluated in single group hybrid implementation‐effectiveness pilot study. Patients were e‐referred from the clinical team to health coaches for three health self‐management coaching calls and received text messages to enhance coaching. Semi‐structured qualitative interviews were conducted with 21 patient participants, 2 referring clinicians, and 2 health coaches to determine intervention acceptability (attitudes, appropriateness, suitability, convenience, and perceived effectiveness) and to identify important elements of the program and potential mechanisms of action to guide future implementation. Results SHARE‐S was described as impactful and convenient. The nondirective, patient‐centered health coaching and mindfulness exercises were deemed most acceptable; text messages were less acceptable. Stakeholders suggested increased flexibility in format, frequency, timing, and length of participation, and additional tailored educational materials. Patients reported tangible health behavior changes, improved mood, and increased accountability and self‐efficacy. Conclusions SHARE‐S is overall an acceptable and potentially effective intervention that may enhance survivors' self‐management and well‐being. Alterations to tailored content, timing, and dose should be tested to determine impact on acceptability and outcomes.

Abstract Background Secreted Frizzled‐Related Protein 5 (SFRP5) modulates Wnt signalling pathways, affecting diverse biological processes. We assessed the diagnostic and prognostic value of circulating SFRP5 (cSFRP5) in colorectal cancer (CRC) Methods Plasma cSFRP5 concentrations were measured using enzyme‐linked immunosorbent assay (ELISA) in healthy donors (n = 133), individuals diagnosed with CRC (n = 449), colorectal polyps (n = 85), and medical conditions in other organs including cancer, inflammation, and benign states (n = 64). Results Patients with CRC, polyps, and other conditions showed higher cSFRP5 levels than healthy individuals (p

Abstract Wildlife space use is a key component to consider when determining effective conservation and management practices. Home range size and resource selection can vary temporally and spatially depending on mortality risks in the area and access to food resources. Lands used for coal mining can contain unique mortality risks and food resources for American black bears (Ursus americanus) relative to surrounding landscapes due to hunting restrictions, vegetation planted as part of the reclamation process, and other anthropogenic food resources. We examined the influence of mining sites on resource selection of female black bears in southern West Virginia, USA, during 2007 and 2008. We estimated home range size with Brownian Bridge movement models and evaluated variation in home range size with mixed‐effects linear regression. We evaluated resource selection with mixed‐effects Poisson point process models. On mine sites, the mean 95% home range for female black bears was 1,996 ha (SD = 2,633) in the autumn and 544 ha (SD = 238) in the spring, and on non‐mine sites the mean 95% home range was 1,926 ha (SD = 1,292) in the autumn and 771 ha (SD = 480) in the spring. Our resource selection model indicated black bears used nonhunting zones associated with mine lands much greater than their availability, and that black bears in mine areas disproportionately used areas in close proximity to anthropogenic structures. Interannual variation in home range size was likely associated with mast conditions, because smaller home ranges were associated with high mast production. Our data suggest black bears may be using non‐hunting zones within mine lands as refugia from hunting and are using anthropogenic food sources available at refuse sites on mine lands, which may increase regional black bear populations in areas with high mining activity.

Abstract Background Clinical presentations of child and adolescent psychopathology can vary systematically for boys and girls. While network analysis is increasingly being applied to explore psychopathology in adults, there is a dearth of network studies considering differences in symptoms for boys and girls, particularly in developmental trauma‐related symptomatology. Methods This study involves rural children (n = 375, 39.47% girls) and adolescents (n = 291, 51.20% girls) involved with child protection services in Ontario, Canada. Caregivers completed the Assessment Checklist for Children or Adolescents within the first 6 months of care. Psychometric network analyses were conducted using subscales for boys and girls. Differences were examined via network comparison permutation tests, moderated network models, and independent t‐tests. Results Attachment‐related interpersonal difficulties were the most central nodes in the child and adolescent networks for both boys and girls. Emotional dysregulation also had high strength centrality for adolescents. While network comparison tests found the overall network structures and global network strength to be invariant between boys and girls for children and adolescents, moderated network models and independent t‐tests revealed several differences with regards to the expression of specific symptoms. Among children, girls exhibited more indiscriminate and pseudomature interpersonal behaviors, whereas boys expressed significantly more non‐reciprocal interpersonal behaviors and self‐injury. Adolescent girls exhibited more behavioral dysregulation and suicide discourse in the moderated network model; t‐tests also indicated higher levels of emotional dysregulation, negative self‐image, and other items considered clinically important complex trauma symptoms (e.g., distrust of adults, confused belonging). Discussion This study supports evidence of differences in the expression of complex trauma symptomatology for boys and girls. Additionally, girls exhibit more symptoms, in general. Consistent with the transdiagnostic conceptualization of the consequences of developmental trauma, findings demonstrate the primacy of attachment‐specific difficulties and emotion dysregulation.

Abstract Objectives To confirm the structural validity of the Recurrent Urinary Tract Infection Symptom Scale (RUTISS), determining whether a bifactor model appropriately fits the questionnaire's structure and identifying areas for refinement. Used in conjunction with established clinical testing methods, this patient‐reported outcome measure addresses the urgent need to validate the patient perspective. Patients and methods A clinically and demographically diverse sample of 389 people experiencing recurrent UTI across 37 countries (96.9% female biological sex, aged 18–87 years) completed the RUTISS online. A bifactor graded response model was fitted to the data, identifying potential items for deletion if they indicated significant differential item functioning (DIF) based on sociodemographic characteristics, contributed to local item dependence or demonstrated poor fit or discrimination capability. Results The final RUTISS comprised a 3‐item symptom frequency section, a 1‐item global rating of change scale and an 11‐item general ‘rUTI symptom and pain severity’ subscale with four sub‐factor domains measuring ‘urinary symptoms’, ‘urinary presentation’, ‘UTI pain and discomfort’ and ‘bodily sensations’. The bifactor model fit indices were excellent (root mean square error of approximation [RMSEA] = 0.041, comparative fit index [CFI] = 0.995, standardised root mean square residual [SRMSR] = 0.047), and the mean‐square fit statistics indicated that all items were productive for measurement (mean square fit indices [MNSQ] = 0.64 – 1.29). Eighty‐one per cent of the common model variance was accounted for by the general factor and sub‐factors collectively, and all factor loadings were greater than 0.30 and communalities greater than 0.60. Items indicated high discrimination capability (slope parameters > 1.35). Conclusion The 15‐item RUTISS is a patient‐generated, psychometrically robust questionnaire that dynamically assesses the patient experience of recurrent UTI symptoms and pain. This brief tool offers the unique opportunity to enhance patient‐centred care by supporting shared decision‐making and patient monitoring.

Abstract Introduction Enteric methane (CH4) emissions are one of the largest components of the anthropogenic CH4 budget, and with accelerating climatic changes, there are calls to reduce anthropogenic greenhouse gas emissions. Certain seaweeds fed as supplements can reduce enteric CH4 emissions from ruminant animals by as much as 80%; however, these studies have yet to analyze downstream impacts that may arise from the deposit of affected manures on pastures or agricultural fields. Materials and Methods Here we conducted a 28‐day soil and manure incubation utilizing manures collected from dairy cows in a seaweed feeding trial to analyze the impacts of manure on greenhouse gas fluxes and nutrient cycling. Cows were fed different diets with a control group (no seaweed supplementation), and a 3% and 6% by dry‐weight seaweed (Chondrus crispus) supplementation. Three soil moisture treatments were also tested, with a field moist capacity [67% gravimetric water content (GWC)], a drier group (50% GWC), and a saturated treatment (84% GWC). Results We found that manure from seaweed‐fed cows reduced emissions of carbon dioxide and had similar emissions of methane and nitrous oxide to the control. Higher moisture levels increased CH4 emissions and nitrous oxide emissions with CH4 emissions trending higher in seaweed supplements trending higher in. Inorganic nitrogen turnover varied more based on moisture levels than seaweed supplements, as did the magnitude of methane and nitrous oxide emissions. Total carbon and nitrogen mostly decreased except in the 3% seaweed supplementation, which increased carbon and nitrogen with a drop in C:N in the 50% GWC group. Conclusion Seaweed supplements may partially reduce climate impacts of manures from cows fed seaweed supplements or at least not cause harm or impact manure quality. Given feeds may reduce enteric CH4 emissions, they may be a part of a successful strategy to reduce climate impacts of cattle.

Abstract Acetamiprid is a pesticide active substance with insecticidal action whose approval was renewed by Commission Implementing Regulation (EU) 2018/113. In January 2022, the EFSA PPR Panel published a statement following a request from the European Commission to advise on human health or the environment based on new scientific evidence presented by France during the decision‐making phase. In July 2022, by means of a further mandate received from the European Commission, EFSA was requested to provide advice if new information and any other scientific evidence that has become available since the assessment conducted for the renewal in 2018 warrant re‐evaluation of (i) toxicological parameters used for the risk assessment of acetamiprid during the renewal process, including toxicological endpoints; (ii) the residue definition for acetamiprid in products of plant origin; and (iii) the safety of existing maximum residue levels (MRLs). Meanwhile, the applicant of acetamiprid in the EU submitted new toxicology studies regarding the toxicological profile of the metabolite IM‐2‐1. Furthermore, the European Commission was made aware that several recent publications in scientific literature were made available after the literature searches conducted by EFSA. As the new data could affect the advice that EFSA was expected to deliver through the 2022 mandate, EFSA was further requested to consider this information by means of a revised mandate received in September 2023. As regards re‐evaluation of point (i) in this statement, this was addressed by an EFSA Working Group integrating all the available evidence. The results of the weight of evidence indicated that there are major uncertainties in the body of evidence for the developmental neurotoxicity (DNT) properties of acetamiprid and further data are therefore needed to come to a more robust mechanistic understanding to enable appropriate hazard and risk assessment. In view of these uncertainties, the EFSA WG proposed to lower the acceptable daily intake (ADI) and acute reference dose (ARfD) from 0.025 to 0.005 mg/kg body weight (per day). A revised residue definition for risk assessment was proposed for leafy and fruit crops as sum of acetamiprid and N‐desmethyl‐acetamiprid (IM‐2‐1), expressed as acetamiprid. Regarding pulses/oilseeds, root crops and cereals, the new data received did not indicate a need to modify the existing residue definition for risk assessment, which therefore remains as parent acetamiprid. Regarding the residue definition for enforcement, the available data did not indicate a need to modify the existing definition because acetamiprid is still a sufficient marker of the residues in all crop groups. Considering the new health‐based guidance values derived in the present statement, a risk for consumer has been identified for 38 MRLs currently in place in the EU Regulation. Consequently, EFSA recommended to lower the existing MRLs for 38 commodities based on the assessment of fall‐back Good Agricultural Practices received within an ad hoc data call. Some fall‐back MRLs proposals require further risk management considerations.

Abstract Scaling patterns in plants have long interested biologists, particularly whether different species share similar patterns of growth, and whether differences in growth trajectories depend on plant size. Using 8,794,737 measurements for 285 species from the U.S. Forest Inventory and Analysis database, we test several predictions emerging from a recently published “flow similarity” model for plant growth and allometry. We show that the model's predicted curvature for intraspecific relationships between height, dbh, and biomass is found in 88.1% of examined cases, and empirical slopes fall as predicted between the elastic similarity and flow similarity predictions in 71.1% of cases. We also find a strong size dependence in observed intraspecific allometric exponents, with large species, particularly gymnosperms, converging near the expectation for elastic similarity and the central tendency among small species approaching the expectations for flow similarity in most cases. Our results support the idea that differences in growth patterns across plant species depend on plant size and their attendant hydraulic and/or biomechanical demands and helps to delineate the bounds of the theoretical morphospace in which they occur.

Abstract Maternally‐inherited sex ratio distorting microbes (SRDMs) are common among arthropod species. Typically, these microbes cause female‐biased sex ratios in host broods, either by; killing male offspring, feminising male offspring, or inducing parthenogenesis. As a result, infected populations can experience drastic ecological and evolutionary change. The mechanism by which SRDMs operate is likely to alter their impact on host evolutionary ecology; despite this, the current literature is heavily biased towards a single mechanism of sex ratio distortion, male‐killing. Furthermore, amidst the growing concerns surrounding the loss of arthropod diversity, research into the impact of SRDMs on the viability of arthropod populations is generally lacking. In this study, using a theoretical approach, we model the epidemiology of an understudied mechanism of microbially‐induced sex ratio distortion—feminisation—to ask an understudied question—how do SRDMs impact extinction risk in a changing environment? We constructed an individual‐based model and measured host population extinction risk under various environmental and epidemiological scenarios. We also used our model to identify the precise mechanism modulating extinction. We find that the presence of feminisers increases host population extinction risk, an effect that is exacerbated in highly variable environments. We also identified transmission rate as the dominant epidemiological trait responsible for driving extinction. Finally, our model shows that sex ratio skew is the mechanism driving extinction. We highlight feminisers and, more broadly, SRDMs as important determinants of the resilience of arthropod populations to environmental change.

Abstract Sweet's syndrome (SS) is a neutrophilic dermatosis characterised by the acute onset of erythematous papules or plaques and a constellation of symptoms including fever, leucocytosis, and histopathology demonstrating nodular, pustular, or diffuse infiltrate of neutrophils with marked papillary oedema. SS can be a manifestation of inflammatory bowel disease and often coincides with periods of disease flares. Only a few cases of SS associated with ulcerative colitis are reported in the literature, and no cases have involved pulmonary manifestations in the paediatric population. We present a case of a 14‐year‐old girl presenting with new onset ulcerative colitis requiring emergent colectomy with subsequent development of pulmonary SS. Treatment consisted of intravenous and oral corticosteroids and dapsone. SS should be considered in the differential diagnosis of prolonged fever with cutaneous involvement and systemic symptoms. Special consideration should be given to paediatric patients with extracutaneous manifestations, particularly pulmonary involvement.

Abstract Differences in the number of alien plant species in different locations may reflect climatic and other controls that similarly affect native species and/or propagule pressure accompanied with delayed spread from the point of introduction. We set out to examine these alternatives for Himalayan plants, in a phylogenetic framework. We build a database of alien plant distributions for the Himalaya. Focusing on the well‐documented regions of Jammu & Kashmir (west) and Bhutan (east) we compare alien and native species for (1) richness patterns, (2) degree of phylogenetic clustering, (3) the extent to which species‐poor regions are subsets of species‐rich regions and (4) continental and climatic affinities/source. We document 1470 alien species (at least 600 naturalised), which comprise ~14% of the vascular plants known from the Himalaya. Alien plant species with tropical affinities decline in richness with elevation and species at high elevations form a subset of those at lower elevations, supporting location of introduction as an important driver of alien plant richness patterns. Separately, elevations which are especially rich in native plant species are also rich in alien plant species, suggesting an important role for climate (high productivity) in determining both native and alien richness. We find no support for the proposition that variance in human disturbance or numbers of native species correlate with alien distributions. Results imply an ongoing expansion of alien species from low elevation sources, some of which are highly invasive.

Abstract The endocannabinoid system is widely expressed throughout the body and is comprised of receptors, ligands, and enzymes that maintain metabolic, immune, and reproductive homeostasis. Increasing interest in the endocannabinoid system has arisen due to these physiologic roles, policy changes leading to more widespread recreational use, and the therapeutic potential of Cannabis and phytocannabinoids. Rodents have been the primary preclinical model of focus due to their relative low cost, short gestational period, genetic manipulation strategies, and gold‐standard behavioral tests. However, the potential for lack of clinical translation to non‐human primates and humans is high as cross‐species comparisons of the endocannabinoid system have not been evaluated. To bridge this gap in knowledge, we evaluate the relative gene expression of 14 canonical and extended endocannabinoid receptors in seven peripheral organs of C57/BL6 mice, Sprague–Dawley rats, and non‐human primate rhesus macaques. Notably, we identify species‐ and organ‐specific heterogeneity in endocannabinoid receptor distribution where there is surprisingly limited overlap among the preclinical models. Importantly, we determined there were no receptors with identical expression patterns among mice (three males and two females), rats (six females), and rhesus macaques (four males). Our findings demonstrate a critical, yet previously unappreciated, contributor to challenges of rigor and reproducibility in the cannabinoid field, which has implications in hampering progress in understanding the complexity of the endocannabinoid system and development of cannabinoid‐based therapies.

Abstract Exposure to extreme temperatures can negatively affect animal reproduction, by disrupting the ability of individuals to produce any offspring (fertility), or the number of offspring produced by fertile individuals (fecundity). This has important ecological consequences, because reproduction is the ultimate measure of population fitness: a reduction in reproductive output lowers the population growth rate and increases the extinction risk. Despite this importance, there have been no large‐scale summaries of the evidence for effect of temperature on reproduction. We provide a systematic map of studies testing the relationship between temperature and animal reproduction. We systematically searched for published studies that statistically test for a direct link between temperature and animal reproduction, in terms of fertility, fecundity or indirect measures of reproductive potential (gamete and gonad traits). Overall, we collated a large and rich evidence base, with 1654 papers that met our inclusion criteria, encompassing 1191 species. The map revealed several important research gaps. Insects made up almost half of the dataset, but reptiles and amphibians were uncommon, as were non‐arthropod invertebrates. Fecundity was the most common reproductive trait examined, and relatively few studies measured fertility. It was uncommon for experimental studies to test exposure of different life stages, exposure to short‐term heat or cold shock, exposure to temperature fluctuations, or to independently assess male and female effects. Studies were most often published in journals focusing on entomology and pest control, ecology and evolution, aquaculture and fisheries science, and marine biology. Finally, while individuals were sampled from every continent, there was a strong sampling bias towards mid‐latitudes in the Northern Hemisphere, such that the tropics and polar regions are less well sampled. This map reveals a rich literature of studies testing the relationship between temperature and animal reproduction, but also uncovers substantial missing treatment of taxa, traits, and thermal regimes. This database will provide a valuable resource for future quantitative meta‐analyses, and direct future studies aiming to fill identified gaps.

Abstract Approved therapies for the treatment of patients with pulmonary arterial hypertension (PAH) mediate pulmonary vascular vasodilatation by targeting distinct biological pathways. International guidelines recommend that patients with an inadequate response to dual therapy with a phosphodiesterase type‐5 inhibitor (PDE5i) and endothelin receptor antagonist (ERA), are recommended to either intensify oral therapy by adding a selective prostacyclin receptor (IP) agonist (selexipag), or switching from PDE5i to a soluble guanylate‐cyclase stimulator (sGCS; riociguat). The clinical equipoise between these therapeutic choices provides the opportunity for evaluation of individualized therapeutic effects. Traditionally, invasive/hospital‐based investigations are required to comprehensively assess disease severity and demonstrate treatment benefits. Regulatory‐approved, minimally invasive monitors enable equivalent measurements to be obtained while patients are at home. In this 2 × 2 randomized crossover trial, patients with PAH established on guideline‐recommended dual therapy and implanted with CardioMEMS™ (a wireless pulmonary artery sensor) and ConfirmRx™ (an insertable cardiac rhythm monitor), will receive ERA + sGCS, or PDEi + ERA + IP agonist. The study will evaluate clinical efficacy via established clinical investigations and remote monitoring technologies, with remote data relayed through regulatory‐approved online clinical portals. The primary aim will be the change in right ventricular systolic volume measured by magnetic resonance imaging (MRI) from baseline to maximal tolerated dose with each therapy. Using data from MRI and other outcomes, including hemodynamics, physical activity, physiological measurements, quality of life, and side effect reporting, we will determine whether remote technology facilitates early evaluation of clinical efficacy, and investigate intra‐patient efficacy of the two treatment approaches.

Abstract Drug regulatory institutions, infrastructures, and systems are becoming increasingly interconnected across national boundaries and increasingly global in outlook. This process is reflected in the broadening and deepening application of the principles and practice of Regulatory Reliance, and parallel initiatives to strengthen the capacities of regulatory institutions in low‐ and middle‐income countries (LMICs). Although these developments are important and constructive, they have tended to be framed in terms of the transfer of systems, knowledge, and skills from relatively “mature” regulatory agencies in high‐income countries (HICs) to less‐well‐resourced regulatory agencies in LMICs. This framing recognizes and foregrounds the considerable practical challenges that many LMIC regulatory agencies face, but in doing so, also backgrounds and underestimates the significance of the different contextual insights that LMIC health researchers and regulators can bring to the regulatory deliberations of their HIC counterparts. This position paper argues that the systematic pursuit, identification, and sharing of these different contextual insights—a dimension of regulatory science that we term “Regulatory Complementarity”—can augment the current practice and goals of Regulatory Reliance, and further invigorate the emerging global regulatory ecosystem.

Abstract Characterization of the interleukin (IL)‐10 knockout (KO) mouse with chronic gut inflammation, cardiovascular dysfunction, and bone loss suggests a critical role for this cytokine in interorgan communication within the gut, bone, and cardiovascular axis. We sought to understand the role of IL‐10 in the cross‐talk between these systems. Six‐week‐old IL‐10 KO mice and their wild type (WT) counterparts were maintained on a standard rodent diet for 3 or 6 months. Gene expression of proinflammatory markers and Fgf23, serum 17β‐estradiol (E2), and cardiac protein expression were assessed. Ileal Il17a and Tnf mRNA increased while Il6 mRNA increased in the bone and heart by at least 2‐fold in IL‐10 KO mice. Bone Dmp1 and Phex mRNA were repressed at 6 months in IL‐10 KO mice, resulting in increased Fgf23 mRNA (~4‐fold) that contributed to increased fibrosis. In the IL‐10 KO mice, gut bacterial β‐glucuronidase activity and ovarian Cyp19a1 mRNA were lower (p

Abstract Successful restoration of human‐disturbed landscapes and ecosystems will be increasingly compromised by the impacts of climate warming. Assisted migration and climate‐informed restoration, in which populations and species adapted to future climates are selected for restoration planting, have emerged as management tools to mitigate climate change effects. However, it is unclear whether climate‐informed restoration could offset the negative effects of climate change and enable successful restoration. We used a forest landscape model to evaluate the potential for reclamation activities to restore western Canadian boreal forest landscapes severely degraded by oil sands mining. We parametrized tree populations adapted to growing in warmer climates and then simulated the planting of local or southern tree populations under different climate change, mining, and wildfire disturbance scenarios. We found that planting trees better adapted to a warmer climate mitigated climate‐change and wildfire‐caused decreases in biomass across the landscape, but only under moderate climate change scenarios. The compensatory effect of planting populations adapted to warmer southern climates disappeared under a more severe climate change scenario. The advantage of planting southern populations also disappeared under wildfire scenarios, generally doubling the biomass loss compared with scenarios without wildfire. With wildfire and strong climate change effects, forest cover disappeared from much of the landscape, regardless of the planting scenario, causing it to change markedly from present‐day continuous boreal forest cover. We argue that such conditions would have large ecological and economic consequences. Scenario modeling with forest landscape models could be used as a tool to identify the long‐term success of restoration actions and to understand possible consequences of climate‐informed restoration.

Abstract Sea‐level rise (SLR) projections by Earth System Models (ESMs) depend on ice sheet surface mass balances. Accurate, global atmosphere reanalyses would be ideal for providing equilibrated ice sheet model initial conditions in fully coupled ESM simulations. Here we present the first evaluation of 1980–1990 global reanalysis precipitation over Greenland and Antarctica that uses independent observations of net accumulation rates derived from shallow ice cores. Precipitation distributions from both the European Centre for Medium‐Range Weather Forecast's Reanalysis (ERA5) and the Modern‐Era Retrospective Analysis for Research and Applications (MERRA‐2) are highly correlated with contemporaneous co‐located net accumulation rates from Greenland (r2 > 0.95) and West Antarctica (r2 > 0.7). Three other commonly used reanalyses (WFDE5, CRUNCEP, and GSWP3) exhibit significantly weaker correlations on one or both ice sheets. Our findings imply that ESMs should use ERA5 or MERRA‐2 in data‐forced simulations to validate ice sheet model dynamics and precondition firn for SLR projections.

Abstract Pulmonary hypertension (PH) is a risk factor for mortality in patients with sarcoidosis. Severe PH in chronic lung disease has previously been defined as mean pulmonary arterial pressure (mPAP) ≥ 35 mmHg or mPAP 25 ≥ mmHg with cardiac index (CI) ≤ 2 L/min/m2. However, there is no clear definition denoting severity of sarcoidosis‐associated PH (SAPH). We aimed to determine pulmonary hemodynamic cut‐off values where transplant‐free survival was worse among patients with SAPH. This was a retrospective cohort analysis of the Registry of SAPH database focusing on pulmonary hemodynamic predictors of transplant‐free survival among patients with precapillary SAPH. Cox regression was performed to determine which pulmonary hemodynamic values predicted death or lung transplantation. Kaplan−Meier survival analysis was performed on statistically significant predictors to determine pulmonary hemodynamic cut‐off values where transplant‐free survival was decreased. Decreased transplant‐free survival occurred among SAPH patients with mPAP ≥ 40 mmHg and SAPH patients with pulmonary vascular resistance (PVR) ≥ 5 Woods units (WU). Transplant‐free survival was not decreased in patients who fulfilled prior criteria of severe PH in chronic lung disease. We identified new cut‐offs with decreased transplant‐free survival in the SAPH population. Neither cut‐off of mPAP ≥ 40 mmHg nor PVR ≥ 5 WU has previously been shown to be associated with decreased transplant‐free survival in SAPH. These values could suggest a new definition of severe SAPH. Our PVR findings are in line with the most recent European Society of Cardiology/European Respiratory Society guideline definition of severe PH in chronic lung disease.

Abstract Social interactions can drive distinct gene expression profiles which may vary by social context. Here we use female sailfin molly fish (Poecilia latipinna) to identify genomic profiles associated with preference behavior in distinct social contexts: male interactions (mate choice) versus female interactions (shoaling partner preference). We measured the behavior of 15 females interacting in a non‐contact environment with either two males or two females for 30 min followed by whole‐brain transcriptomic profiling by RNA sequencing. We profiled females that exhibited high levels of social affiliation and great variation in preference behavior to identify an order of magnitude more differentially expressed genes associated with behavioral variation than by differences in social context. Using a linear model (limma), we took advantage of the individual variation in preference behavior to identify unique gene sets that exhibited distinct correlational patterns of expression with preference behavior in each social context. By combining limma and weighted gene co‐expression network analyses (WGCNA) approaches we identified a refined set of 401 genes robustly associated with mate preference that is independent of shoaling partner preference or general social affiliation. While our refined gene set confirmed neural plasticity pathways involvement in moderating female preference behavior, we also identified a significant proportion of discovered that our preference‐associated genes were enriched for ‘immune system’ gene ontology categories. We hypothesize that the association between mate preference and transcriptomic immune function is driven by the less well‐known role of these genes in neural plasticity which is likely involved in higher‐order learning and processing during mate choice decisions.

Abstract Cirrus clouds provide a significant radiative forcing on the Earth's climate system. This paper looks at the connection in space and time between monthly mean lightning activity observed from the Lightning Imaging Sensor on board the International Space Station, and the global monthly mean cirrus cloud cover obtained from the MERRA‐2 reanalysis product. The correlation coefficient between the global monthly mean cloud optical thickness of the cirrus clouds (clouds at altitudes above the 400 hPa pressure levels) with the monthly mean lightning flash counts is 0.84, implying that monthly mean lightning can explain 70% of monthly variability of the global high cloud optical thickness. In addition, lightning amount explains nearly 60% of the monthly mean global area coverage of cirrus clouds. Given these statistically significant connections between lightning and cirrus clouds, we propose using global lightning data as an additional tool for monitoring monthly variability of cirrus clouds.

Abstract The hydroacoustic environment of a rapidly warming Arctic Ocean will be impacted by interconnected changes in the physical environment and increased human activity. Previous acoustic calculations will need to be updated to reflect current and future conditions. Earth System Models are important tools for making projections of changes in a wide range of physical processes under future climates. We present a comparison of Arctic acoustic travel times based on output from the Department of Energy's Energy Exascale Earth System Model with measured travel times from the 2016–2017 Canada Basin Acoustic Propagation Experiment and with travel times predicted by empirical temperature and salinity observations. This comparison allows us to test the impact of changes in Arctic sound speed profiles on acoustic travel times and connects Arctic hydroacoustics with the changing Arctic environment as described by a climate model.

Abstract Geochemical analyses of carbonate minerals yield multiple parameters which can be used to estimate the temperature and water composition at which they formed. Analysis of fluid trapped in minerals is a potentially powerful tool to reconstruct paleotemperatures as well as diagenetic and hydrothermal processes, as these could represent the parent fluid. Internal fluids play important roles during the alteration of carbonate fossils, lowering energetic barriers associated with resetting of clumped isotopes, as well as mediating the transport of elements during diagenesis. Here, we explore the behavior of the ∆47–∆48 “dual‐clumped” isotope thermometer during fluid‐carbonate interaction and demonstrate that it is highly sensitive to the water/carbonate ratio, behaving as a linear system in “rock buffered” alteration, and as a decoupled system in water‐dominated systems due to non‐linear mixing effects in ∆48. Dry heating experiments show that the extrapolated “heated” end‐member is indistinguishable from the predicted ∆47 and ∆48 value expected for the experimental temperature. Furthermore, we evaluate two common laboratory sampling methods for their ability to thermally alter samples. We find that the temperature of the commonly used crushing cells used to vapourize water for fluid inclusion δ18O analyses is insufficient to cause fluid‐carbonate oxygen isotope exchange, demonstrating its suitability for analyses of fluid inclusions in carbonates. We also find that belemnites sampled with a hand‐drill yield significantly warmer paleotemperatures than those sampled with mortar and pestle. We conclude that thermally‐driven internal fluid‐carbonate exchange occurs indistinguishably from isotopic equilibrium, limited by the extent to which internal water and carbonate can react.