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Abstract Background Hypoadrenocorticism in cats is uncommonly reported. Most reports consist of cats with hyponatremia, hyperkalemia, or both. Hypothesis/Objectives To describe clinical findings, treatment response, and outcome in cats diagnosed with hypoadrenocorticism, including cats with abnormal and normal serum sodium and potassium concentrations. Animals Forty‐one cats with hypoadrenocorticism; 36 with and 5 without abnormal serum sodium and potassium concentrations. Methods Multicenter retrospective observational study. Data for the entire cohort were assessed using descriptive statistics and differences between cats with and without abnormal serum sodium and potassium concentrations were evaluated. Results Median age was 5.7 years (range, 0.2‐13.8). Twenty‐three (56%) cats were male and 18 (44%) were female. Cats with hyponatremia, hyperkalemia, or both were less likely to have a history of vomiting (P = .01) but more likely to be hypothermic (P = .03), dehydrated (P = .04) or weak (P = .04) on examination, compared with nonhyponatremic and nonhyperkalemic cats. Frequency of hypercalcemia was 31.7%. Exocrine pancreatic insufficiency (EPI) was diagnosed in 4/7 cats tested; all 4 had concurrent cobalamin deficiency. Thirty‐five (85.4%) cats survived to discharge. In 2 cats, hypoadrenocorticism occurred secondary to lymphoma. Median survival time (MST) for all‐cause mortality was 2035 days (95% confidence interval [CI], 294‐4380 days); MST for disease‐specific mortality was not reached. Conclusions and Clinical Importance Approximately one‐third of cats with hypoadrenocorticism had hypercalcemia. In some cases, hyponatremia and hyperkalemia were not observed. Cats with nonneoplastic associated hypoadrenocorticism that survive initial hospitalization can have a favorable long‐term prognosis. Testing for EPI may be warranted in cats with hypoadrenocorticism.

ABSTRACT Biological invasions pose significant threats to ecological and economic stability, with invasive pests like the Asian longhorned beetle (Anoplophora glabripennis Motschulsky, ALB) causing substantial damage to forest ecosystems. Effective pest management relies on comprehensive knowledge of the insect's biology and invasion history. This study uses genomics to address these knowledge gaps and inform existing biosurveillance frameworks. We used 2768 genome‐wide single nucleotide polymorphisms to compare invasive A. glabripennis populations in North America, using genomic variation to trace their sources of invasion and spread patterns, thereby refining our understanding of this species' invasion history. We found that most North American A. glabripennis infestations were distinct, resulting from multiple independent introductions from the native range. Following their introduction, all invasive populations experienced a genetic bottleneck which was followed by a population expansion, with a few also showing secondary spread to satellite infestations. Our study provides a foundation for a genome‐based biosurveillance tool that can be used to clarify the origin of intercepted individuals, allowing regulatory agencies to strengthen biosecurity measures against this invasive beetle.

Abstract Public policy addressing biodiversity loss is most likely to be effective when it is informed by appropriate evidence and considers potential unintended consequences. We evaluate key evidence relating to the Hunting Trophies (Import Prohibition) Bill that was discussed in the UK Parliament between 2022 and 2024. We characterize the UK's role in international hunting trophy trade by analyzing CITES (Convention on International Trade in Endangered Species of Wild Fauna and Flora) trade data for 2000–2021 and 2015–2021. For CITES‐listed species imported to/exported from the UK as hunting trophies in these periods we use data from the International Union for Conservation of Nature (IUCN) Red List of Threatened Species to determine whether hunting designated as “trophy hunting” is (i) likely a major threat contributing to species being of elevated conservation concern, (ii) likely or possibly causing localized declines, or (iii) not a threat. We then use the Red List to determine whether such hunting provides, or potentially provides, benefits for species and/or people. Finally, we evaluate the UK Government's impact assessment of the bill. In 2000–2021 an estimated 3494 hunting trophies from 73 CITES‐listed species and subspecies were exported to the UK involving an estimated 2549 whole organism equivalents (WOEs), that is, individual animals. Imports involved 158.86 ± 66.53 (mean ± SD) trophies/year (115.83 ± 32.27 WOEs/year). In 2015–2021, 79% of imports were from countries where populations of the hunted species are stable, increasing, or abundant. Legal hunting for trophies is not a major threat to any of the species or subspecies imported to the UK, but likely or possibly represents a local threat to some populations of eight species. This hunting does, or could potentially, benefit 20 species and subspecies, and people. Among other concerns, the impact assessment failed to adequately consider the costs and benefits to local communities in countries where such hunting occurs. Informed by these analyses we discuss alternative regulatory options.

Abstract Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local‐to‐global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local‐to‐local BA4 – MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local‐to‐global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD.

Abstract The androgen receptor (AR) is an attractive target for treating prostate cancer, considering its role in the development and progression of localized and metastatic prostate cancer. The high global mortality burden of prostate cancer, despite medical treatments such as androgen deprivation or AR antagonist therapy, highlights the need to explore alternative strategies. One strategy involves the use of heterobifunctional degraders, also known as proteolysis‐targeting chimeras, which are novel small‐molecule therapeutics that inhibit amplified or mutated targets. Here, the study reports a novel cereblon‐based AR degrader, UBX‐390, and demonstrates its superior activity over established AR degraders, such as ARV‐110 or ARCC‐4, in prostate cancer cells under short‐ and long‐term treatment conditions. UBX‐390 suppresses chromatin binding and gene expression of AR and demonstrates substantial efficacy in the degradation of AR mutants in patients with treatment‐resistant prostate cancer. UBX‐390 is presented as an optimized AR degrader with remarkable potential for treating castration‐resistant prostate cancer.

Abstract Passive acoustic recorders have emerged as powerful tools for ecological monitoring. However, effective monitoring is not simply an act of recording sounds. To have meaning for conservation and management, acoustic monitoring needs to be properly planned and analyzed to yield high quality information. Here, we provide a set of considerations for the design of an effective acoustic monitoring program. We argue that such a program, has the following attributes: (1) has established appropriate partnerships with landowners, Traditional Owners, researchers, or other relevant stakeholders, (2) is based on clear objectives and questions, (3) is explicit in its target sound signals, (4) has considered in‐field sensor placement for a range of factors, including experimental design, statistical power, background noise, and potential impacts on human privacy and animal disturbance, (5) has a justified recording schedule and periodicity, (6) has methods to process sound data in line with objectives, and (7) has protocols for permanent data storage and access. Acoustic monitoring is increasingly used in large‐scale programs and will be important in addressing global biodiversity targets and new biodiversity markets. It is critical that new monitoring programs are designed to effectively and efficiently capture data that address pertinent and emerging issues in conservation.

Abstract Background A previous phase IB/II study of nab‐paclitaxel + cisplatin + gemcitabine (NABPLAGEM) in 25 patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC) demonstrated favorable results. This phase II study was conducted to further evaluate the safety, efficacy, and impact on quality of life (QOL) of NABPLAGEM in a multi‐center setting. Methods Participants were ≥18 years; had measurable PDAC; Karnofsky performance status of ≥70%; life expectancy ≥12 weeks;

Abstract The observed partitioning of poleward heat transport between atmospheric and oceanic heat transports (AHT and OHT) is compared to that in coupled climate models. Model ensemble mean poleward OHT is biased low in both hemispheres, with the largest biases in the Southern Hemisphere extratropics. Poleward AHT is biased high in the Northern Hemisphere, especially in the vicinity of the peak AHT near 40°N. The significant model biases are persistent across three model generations (CMIP3, CMIP5, CMIP6) and are insensitive to the satellite radiation and atmospheric reanalyzes products used to derive observational estimates of AHT and OHT. Model biases in heat transport partitioning are consistent with biases in the spatial structure of energy input to the ocean and atmosphere. Specifically, larger than observed model evaporation in the tropics adds excess energy to the atmosphere that drives enhanced poleward AHT at the expense of weaker OHT.

Abstract Engrailed‐1 (EN1) is a critical homeodomain transcription factor (TF) required for neuronal survival, and EN1 expression has been shown to promote aggressive forms of triple negative breast cancer. Here, it is reported that EN1 is aberrantly expressed in a subset of pancreatic ductal adenocarcinoma (PDA) patients with poor outcomes. EN1 predominantly repressed its target genes through direct binding to gene enhancers and promoters, implicating roles in the activation of MAPK pathways and the acquisition of mesenchymal cell properties. Gain‐ and loss‐of‐function experiments demonstrated that EN1 promoted PDA transformation and metastasis in vitro and in vivo. The findings nominate the targeting of EN1 and downstream pathways in aggressive PDA.

Abstract The influence of climate feedbacks on regional hydrological changes under warming is poorly understood. Here, a moist energy balance model (MEBM) with a Hadley Cell parameterization is used to isolate the influence of climate feedbacks on changes in zonal‐mean precipitation‐minus‐evaporation (P − E) under greenhouse‐gas forcing. It is shown that cloud feedbacks act to narrow bands of tropical P − E and increase P − E in the deep tropics. The surface‐albedo feedback shifts the location of maximum tropical P − E and increases P − E in the polar regions. The intermodel spread in the P − E changes associated with feedbacks arises mainly from cloud feedbacks, with the lapse‐rate and surface‐albedo feedbacks playing important roles in the polar regions. The P − E change associated with cloud feedback locking in the MEBM is similar to that of a climate model with inactive cloud feedbacks. This work highlights the unique role that climate feedbacks play in causing deviations from the “wet‐gets‐wetter, dry‐gets‐drier” paradigm.

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

Background The ADAPTABLE (Aspirin Dosing: A Patient‐Centric Trial Assessing Benefits and Long‐Term Effectiveness) was a large, pragmatic, randomized controlled trial that found no difference between high‐ versus low‐dose aspirin for secondary prevention of atherosclerotic cardiovascular disease. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods and Results Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). The primary effectiveness end point was a composite of death, myocardial infarction, or stroke; and the primary safety end point was major bleeding requiring blood transfusions. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non‐P2Y12 groups. Of 13 815 (91.6%) participants with available data, 3051 (22.1%) were receiving clopidogrel (2849 [93.4%]) or prasugrel (203 [6.7%]) at baseline. P2Y12 inhibitor use was associated with higher risk of the primary effectiveness end point (10.86% versus 6.31%; adjusted hazard ratio [HR], 1.40 [95% CI, 1.22–1.62]) but was not associated with bleeding (0.95% versus 0.53%; adjusted HR, 1.42 [95% CI, 0.91–2.22]). We found no interaction in the relative effectiveness and safety of high‐ versus low‐dose aspirin by P2Y12 inhibitor use. Overall, dose switching or discontinuation was more common in the high‐dose compared with low‐dose aspirin group, but the pattern was not modified by P2Y12 inhibitor use. Conclusions In this prespecified analysis of ADAPTABLE, we found that the relative effectiveness and safety of high‐ versus low‐dose aspirin was not modified by baseline P2Y12 inhibitor use. Registration https://www.clinical.trials.gov. Unique identifier: NCT02697916.

Abstract Diverse geographic, environmental, and ecological factors affect gene flow and adaptive genomic variation within species. With recent advances in landscape ecological modelling and high‐throughput DNA sequencing, it is now possible to effectively quantify and partition their relative contributions. Here, we use landscape genomics to identify determinants of genomic differentiation in the forest tent caterpillar, Malacosoma disstria, a widespread and irruptive pest of numerous deciduous tree species in North America. We collected larvae from multiple populations across Eastern Canada, where the species experiences a diversity of environmental gradients and feeds on a number of different host tree species, including trembling aspen (Populus tremuloides), sugar maple (Acer saccharum), red oak (Quercus rubra), and white birch (Betula papyrifera). Using a combination of reciprocal causal modelling (RCM) and distance‐based redundancy analyses (dbRDA), we show that differentiation of thousands of genome‐wide single nucleotide polymorphisms (SNPs) among individuals is best explained by a combination of isolation by distance, isolation by environment (spatial variation in summer temperatures and length of the growing season), and differences in host association. Configuration of suitable habitat inferred from ecological niche models was not significantly related to genomic differentiation, suggesting that M. disstria dispersal is agnostic with respect to habitat quality. Although population structure was not discretely related to host association, our modelling framework provides the first molecular evidence of host‐associated differentiation in M. disstria, congruent with previous documentation of reduced growth and survival of larvae moved between natal host species. We conclude that ecologically mediated selection is contributing to variation within M. disstria, and that divergent adaptation related to both environmental conditions and host association should be considered in ongoing research and management of this important forest pest.

Abstract Given the key role that atmospheric heat transport plays in Earth's climate system, efforts to document its changes over the satellite era are valuable. Clark et al. (2022, https://doi.org/10.1029/2022GL098822) calculated trends in atmospheric heat transport among four reanalysis data sets and found substantial disagreements between data sets. However, after accounting for the lack of mass‐conservation in reanalysis data sets, we find much smaller magnitude trends, with much better agreement among reanalyses. This highlights the importance of mass corrections when calculating atmospheric heat transport.

Abstract Background Involving service users in inpatient care and recovery planning has gained interest worldwide. Our purpose was to evaluate the process of implementation of a coproduced Recovery Guide (RG) intervention in 22 inpatient wards in Sweden, in terms of context, implementation process and mechanisms of impact over 12 months. Methods A mixed method design and a process evaluation framework were used to guide data collection and to deductively analyze perspectives and descriptive statistics of delivery from three stakeholder groups. Results Results showed that although initial contextual barriers were present (e.g., lack of resources, and interest, uncertainty in the organization, a dominant illness perspective), it was possible to implement the RG in 14 wards, where 53% of admitted service users received the intervention. Legitimacy of the intervention, engaged managers and staff, capacity of staff and ward organization, coproduction and continuous support from user organization were critical mediators. Mechanisms of impact concerned (1) a new perspective on mental health, well‐being and recovery, (2) capacity building of a recovery approach in inpatient settings and (3) a meaningful outlet for users' thoughts and feelings on recovery, sharing narratives and influencing care and goals. Conclusions The RG intervention has the potential to promote a recovery approach in inpatient mental health services (MHSs). Coproduction among stakeholders created trust and a sustainable implementation that made it possible for wards to resume implementation when contextual barriers had been resolved. Patient and Public Contribution The current study involved stakeholders including a service user organization, the public, first‐line managers and staff (including peer support workers) in inpatient and community MHS and researchers, who greatly contributed to the implementation programme, including codesign of the RG intervention as well as coproduction of the implementation in inpatient MHS. All authors have their own lived experiences of mental health problems as a service user or as a relative.

Abstract Human‐assisted movement has allowed the Asian longhorned beetle (ALB, Anoplophora glabripennis (Motschulsky)) to spread beyond its native range and become a globally regulated invasive pest. Within its native range of China and the Korean peninsula, human‐mediated dispersal has also caused cryptic translocation of insects, resulting in population structure complexity. Previous studies used genetic methods to detangle this complexity but were unable to clearly delimit native populations which is needed to develop downstream biosurveillance tools. We used genome‐wide markers to define historical population structure in native ALB populations and contemporary movement between regions. We used genotyping‐by‐sequencing to generate 6102 single‐nucleotide polymorphisms (SNPs) and amplicon sequencing to genotype 53 microsatellites. In total, we genotyped 712 individuals from ALB’s native distribution. We observed six distinct population clusters among native ALB populations, with a clear delineation between northern and southern groups. Most of the individuals from South Korea were distinct from populations in China. Our results also indicate historical divergence among populations and suggest limited large‐scale admixture, but we did identify a restricted number of cases of contemporary movement between regions. We identified SNPs under selection and describe a clinal allele frequency pattern in a missense variant associated with glycerol kinase, an important enzyme in the utilization of an insect cryoprotectant. We further demonstrate that small numbers of SNPs can assign individuals to geographic regions with high probability, paving the way for novel ALB biosurveillance tools.

Abstract The UK government is considering legislation to prohibit the importation of hunting trophies. We examine documented social, ecological, and political outcomes of two previous such bans. We find that the UK government's proposal shares the shortcomings of existing bans that have (1) failed to address, or have even amplified, key threats to hunted species, (2) imposed costs on citizens of other countries, and (3) delegitimized the Convention on International Trade in Endangered Species (CITES). Trophy import bans are blunt policy instruments that can cause more problems than they solve.

Abstract Objectives Cerebral palsy (CP) is the most common childhood motor disability, yet its link to single‐gene disorders is under‐characterized. To explore the genetic landscape of CP, we conducted whole exome sequencing (WES) in a cohort of patients with CP. Methods We performed comprehensive phenotyping and WES on a prospective cohort of individuals with cryptogenic CP (who meet criteria for CP; have no risk factors), non‐cryptogenic CP (who meet criteria for CP; have at least one risk factor), and CP masqueraders (who could be diagnosed with CP, but have regression/progressive symptoms). We characterized motor phenotypes, ascertained medical comorbidities, and classified brain MRIs. We analyzed WES data using an institutional pipeline. Results We included 50 probands in this analysis (20 females, 30 males). Twenty‐four had cryptogenic CP, 20 had non‐cryptogenic CP, five had CP masquerader classification, and one had unknown classification. Hypotonic‐ataxic subtype showed a difference in prevalence across the classification groups (p = 0.01). Twenty‐six percent of participants (13/50) had a pathogenic/likely pathogenic variant in 13 unique genes (ECHS1, SATB2, ZMYM2, ADAT3, COL4A1, THOC2, SLC16A2, SPAST, POLR2A, GNAO1, PDHX, ACADM, ATL1), including one patient with two genetic disorders (ACADM, PDHX) and two patients with a SPAST‐related disorder. The CP masquerader category had the highest diagnostic yield (n = 3/5, 60%), followed by the cryptogenic CP category (n = 7/24, 29%). Fifteen percent of patients with non‐cryptogenic CP (n = 3/20) had a Mendelian disorder on WES. Interpretation WES demonstrated a significant prevalence of Mendelian disorders in individuals clinically diagnosed with CP, including in individuals with known CP risk factors.

Abstract Neuromorphic engineering has emerged as a promising research field that can enable efficient and sophisticated signal transmission by mimicking the biological nervous system. This paper presents an artificial nervous system capable of facile self‐regulation via multiplexed complementary signals. Based on the tunable nature of the Schottky barrier of a complementary signal integration circuit, a pair of complementary signals is successfully integrated to realize efficient signal transmission. As a proof of concept, a feedback‐based blood glucose level control system is constructed by incorporating a glucose/insulin sensor, a complementary signal integration circuit, an artificial synapse, and an artificial neuron circuit. Certain amounts of glucose and insulin in the initial state are detected by each sensor and reflected as positive and negative amplitudes of the multiplexed presynaptic pulses, respectively. Subsequently, the pulses are converted to postsynaptic current, which triggered the injection of glucose or insulin in a way that confined the glucose level to a desirable range. The proposed artificial nervous system demonstrates the notable potential of practical advances in complementary control engineering.

Abstract Fauna surveys are traditionally manual, and hence limited in scale, expensive and labour‐intensive. Low‐cost hardware and storage mean that acoustic recording now has the potential to efficiently build scale in terrestrial fauna surveys, both spatially and temporally. With this aim, we have constructed the Australian Acoustic Observatory. It provides a direct and permanent record of terrestrial soundscapes through continuous recording across Australian ecoregions, including those periodically subject to fire and flood, when manual surveys are dangerous or impossible. The observatory comprises 360 permanent listening stations deployed across Australia. Groups of four sensors are deployed at each of 90 sites, placed strategically across ecoregions, to provide representative datasets of soundscapes. Each station continuously records sound, resulting in year‐round data collection. All data are made freely available under an open access licence. The Australian Acoustic Observatory is the world's first terrestrial acoustic observatory of this size. It provides continental‐scale environmental monitoring of unparalleled spatial extent, temporal resolution and archival stability. It enables new approaches to understanding ecosystems, long‐term environmental change, data visualization and acoustic science that will only increase in scientific value over time, particularly as others replicate the design in other parts of the world.

Abstract Wild meat alternatives projects addressing unsustainable hunting by providing alternative foods to wild meat are commonplace across many parts of the Global South. However, understanding their possible conservation and social outcomes prior to implementation is vital, to ensure that they are well designed, that scarce funds are correctly directed, and that the intended outcomes of the project are achievable. We used scenario‐based interviews to explore the potential effects of six hypothetical wild meat alternatives projects in Cameroon on household rates of hunting and consumption over five years. We conducted 171 interviews across four rural villages around the Dja Faunal Reserve in Cameroon, and investigated how the alternative food offered, the addition of income‐generating opportunities, and the scale at which the project was implemented would affect people's willingness and ability to participate. Predicted household rates of hunting and consumption reduced the most under wild meat alternatives projects that offered both food and income‐generating activities. However, this depends on the project being offered at the household, rather than the community, level. Community‐level wild meat alternatives projects only resulted in marginal reductions in hunting and consumption compared to the current baseline and, as such, in this study area community‐level projects are unlikely to achieve their intended conservation goals. These results illustrate the importance of effective dialogue with communities to explore not only their preferences, but also the characteristics of preferred and successful wild meat alternatives projects, before the project design is finalized and implemented. Our findings provide an understanding of the characteristics of wild meat alternatives projects preferred by communities around the Dja Faunal Reserve, using a generalisable approach. We identify factors that may undermine the success of wild meat alternatives projects in rural areas, and provide guidance to conservation practitioners seeking to develop similar projects in future.

Abstract Projects providing alternative foods to wild meat in rural areas are commonplace across West and Central Africa to try and curb unsustainable hunting, regarded as a major concern for conservation and local food security. However, there lacks locally specific research on the preferences and drivers of wild meat consumption in rural areas—essential information for guiding such interventions. We carry out semi‐structured interviews with 542 people in four rural villages around the Dja Faunal Reserve in Cameroon, to understand the importance of wild meat, explore people's food choices, identify the drivers of wild meat consumption, and explore variation in the drivers and barriers to eating wild meat and its alternatives. We found that wild meat is preferred to meat from domestic livestock or wild caught fish. Many of the most commonly preferred wild meat species (porcupine and blue duiker) are relatively abundant, with the exception of pangolin which is globally endangered but which people reportedly prefer because of its good taste. Good taste, perceived health benefits, and easy accessibility are the key drivers of consumption, while taboos, an off‐putting appearance, and health concerns play a strong role in species avoidance, particularly for great apes and large ungulates. Village‐level differences in the drivers of consumption were observed, possibly influenced by their proximity to the reserve, to markets, participation in alternatives projects, and to law enforcement. That people in rural Cameroon care about health and taste in their choices, rather than simply availability or cost, challenges the assumptions that underpin many alternative meat projects. Our findings provide an understanding of consumer drivers to help to guide wild meat alternative interventions in rural areas. We urge wild meat alternatives designers to account for the heterogeneity of preferences and drivers within communities, to help ensure that projects reach both their conservation and social objectives.

Abstract Background Acute exacerbations of asthma are common in children. Multiple asthma severity scores exist, but current emergency department (ED) use of severity scores is not known. Methods A systematic review was undertaken to identify the parameters collected in pediatric asthma severity scores. A survey of Paediatric Emergency Research in the United Kingdom and Ireland (PERUKI) sites was undertaken to ascertain routinely collected asthma data and information about severity scores. Included studies examined severity of asthma exacerbation in children 5–18 years of age with extractable severity parameters. Results Sixteen articles were eligible, containing 17 asthma severity scores. The severity scores assessed combinations of 15 different parameters (median, 6; range, 2–8). The most common parameters considered were expiratory wheeze (15/17), inspiratory wheeze (13/17), respiratory rate (10/17), and general accessory muscle use (9/17). Fifty‐nine PERUKI centers responded to the questionnaire. Twenty centers (33.1%) currently assess severity, but few use a published score. The most commonly recorded routine data required for severity scores were oxygen saturations (59/59, 100%), heart rate, and respiratory rate (58/59, 98.3% for both). Among well‐validated scores like the Pulmonary Index Score (PIS), Pediatric Asthma Severity Score (PASS), Childhood Asthma Score (CAS), and the Pediatric Respiratory Assessment Measure (PRAM), only 6/59 (10.2%), 3/59 (5.1%), 1/59 (1.7%), and 0 (0%) of units respectively routinely collect the data required to calculate them. Conclusion Standardized published pediatric asthma severity scores are infrequently used. Improved routine data collection focusing on the key parameters common to multiple scores could improve this, facilitating research and audit of pediatric acute asthma.

Abstract In recent years, passive acoustic monitoring has emerged as a reliable method for monitoring soniferous fauna, with numerous studies finding estimates of species richness and community composition are comparable with estimates derived from conventional field surveys. Most of these studies compare point counts of forest bird communities with contemporaneous short‐duration acoustic recordings, but several questions remain. How do these two methods compare in more open, arid ecosystems, how does applying methods optimally influence comparisons, and how do patterns in acoustically detectable species compare with overall patterns? Here we demonstrate techniques for improving sampling of acoustic data and conduct acoustic surveys to estimate species richness from ephemeral creek‐lines in the Australian arid zone using a long‐term passively derived acoustic dataset. We examine these results in the context of long‐term observer‐based transect surveys conducted along the same creek‐lines to define species within the avian assemblage that are acoustically detectable or acoustically undetectable/cryptic. Our data suggest that some species were consistently missed by acoustic surveys, but most belonged to groups that are typically excluded from inventories prior to analysis including rare species, raptors, waterbirds, swallows and nocturnal birds. Further, the relative diversities of sites were well estimated by acoustic surveys, with variations between sites reflecting those estimated by observer‐based field surveys. This suggests that in our study system, acoustically detectable species are reliable indicators of overall species richness. Field‐based surveys will remain an important component of sampling in arid ecosystems and we highlight the value of applying acoustic and conventional field‐based surveys in a complementary manner. This approach allows large, publishable datasets to be generated by exploiting the temporal reach of acoustic sensors, while also maximizing detections of acoustically cryptic species via field‐based surveys. We argue that acoustic monitoring has the potential to facilitate greater research effort in largely research‐deficient arid ecosystems.

Abstract We have initiated a single center phase I study in patients with hematologic malignancies progressively substituting day +4 posttransplant cyclophosphamide (PT‐CY) with bendamustine (PT‐BEN) following myeloablative conditioning (MAC) and T‐cell replete haploidentical bone marrow transplantation (haplo‐BMT). We report herein our interim analysis of our first three cohorts PT‐CY (mg/kg)/PT‐BEN (mg/m2): 40/20, 20/60, and 0/90. All patients have tolerated PT‐CY/BEN well with no dose limiting toxicities. Compared to contemporaneous controls undergoing haplo‐BMT with the same MAC regimens but only PT‐CY, we have observed earlier trilineage engraftment (P = .002 neutrophils, P = .014 platelets) and a lower incidence of cytomegalovirus reactivation (P = .016) in the PT‐CY/BEN cohorts. After substituting day +4 PT‐CY with PT‐BEN, the registered trial (www.clinicaltrials.gov; NCT02996773) is proceeding to replace day +3 PT‐CY with PT‐BEN with a view to identifying further evidence on the potential advantages of PT‐BEN.

Abstract North American freshwater mussel species have experienced substantial range fragmentation and population reductions. These impacts have the potential to reduce genetic connectivity among populations and increase the risk of losing genetic diversity. Thirteen microsatellite loci and an 883 bp fragment of the mitochondrial ND1 gene were used to assess genetic diversity, population structure, contemporary migration rates, and population size changes across the range of the Sheepnose mussel (Plethobasus cyphyus). Population structure analyses reveal five populations, three in the Upper Mississippi River Basin and two in the Ohio River Basin. Sampling locations exhibit a high degree of genetic diversity and contemporary migration estimates indicate that migration within river basins is occurring, although at low rates, but there is no migration is occurring between the Ohio and Mississippi river basins. No evidence of bottlenecks was detected, and almost all locations exhibited the signature of population expansion. Our results indicate that although anthropogenic activity has altered the landscape across the range of the Sheepnose, these activities have yet to be reflected in losses of genetic diversity. Efforts to conserve Sheepnose populations should focus on maintaining existing habitats and fostering genetic connectivity between extant demes to conserve remaining genetic diversity for future viable populations.

Background Unlike patients with low ejection fraction after an acute coronary syndrome (ACS), little is known about the long‐term incidence and influence of cardiovascular events before sudden death among stabilized patients after ACS. Methods and Results A total of 18 144 patients stabilized within 10 days after ACS in IMPROVE‐IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) were studied. Cumulative incidence rates (IRs) and IRs per 100 patient‐years of sudden death were calculated. Using Cox proportional hazards, the association of ≥1 additional postrandomization cardiovascular events (myocardial infarction, stroke, and hospitalization for unstable angina or heart failure) with sudden death was examined. Early (≤1 year after ACS) and late sudden deaths (>1 year) were compared. Of 2446 total deaths, 402 (16%) were sudden. The median time to sudden death was 2.7 years, with 109 early and 293 late sudden deaths. The cumulative IR was 2.47% (95% CI, 2.23%–2.73%) at 7 years of follow‐up. The risk of sudden death following a postrandomization cardiovascular event (150/402 [37%] sudden deaths; median 1.4 years) was greater (IR/100 patient‐years, 1.45 [95% CI, 1.23–1.69]) than the risk with no postrandomization cardiovascular event (IR/100 patient‐years, 0.27 [95% CI, 0.24–0.30]). Postrandomization myocardial infarction (hazard ratio [HR], 3.64 [95% CI, 2.85–4.66]) and heart failure (HR, 4.55 [95% CI, 3.33–6.22]) significantly increased future risk of sudden death. Conclusions Patients stabilized within 10 days of an ACS remain at long‐term risk of sudden death with the greatest risk in those with an additional cardiovascular event. These results refine the long‐term risk and risk effectors of sudden death, which may help clinicians identify opportunities to improve care. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00202878.

Background. Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic variants of the GLA gene. Heterozygous female patients may show much more variability in clinical manifestations, ranging from asymptomatic to full-blown disease. Because of this heterogeneous clinical picture in women, the diagnosis of FD has typically been delayed for more than a decade, and the optimal time to initiate treatment remains controversial. Case Presentation. Here, we present two unrelated female patients diagnosed with FD harbouring the same pathogenic GLA variant. We discuss the implications of initiating specific therapy at different stages of the disease, with and without organ involvement (early versus late therapeutic intervention). Conclusions. These clinical cases suggest that initiating specific treatment at an earlier age in women with FD may prevent organ involvement and associated clinical events.

Abstract The world's forests face unprecedented threats from invasive insects and pathogens that can cause large irreversible damage to the ecosystems. This threatens the world's capacity to provide long‐term fiber supply and ecosystem services that range from carbon storage, nutrient cycling, and water and air purification, to soil preservation and maintenance of wildlife habitat. Reducing the threat of forest invasive alien species requires vigilant biosurveillance, the process of gathering, integrating, interpreting, and communicating essential information about pest and pathogen threats to achieve early detection and warning and to enable better decision‐making. This process is challenging due to the diversity of invasive pests and pathogens that need to be identified, the diverse pathways of introduction, and the difficulty in assessing the risk of establishment. Genomics can provide powerful new solutions to biosurveillance. The process of invasion is a story written in four chapters: transport, introduction, establishment, and spread. The series of processes that lead to a successful invasion can leave behind a DNA signature that tells the story of an invasion. This signature can help us understand the dynamic, multistep process of invasion and inform management of current and future introductions. This review describes current and future application of genomic tools and pipelines that will provide accurate identification of pests and pathogens, assign outbreak or survey samples to putative sources to identify pathways of spread, and assess risk based on traits that impact the outbreak outcome.

Abstract 6β‐Hydroxy‐21‐desacetyl deflazacort (6β‐OH‐21‐desDFZ) is a major circulating but not biologically active metabolite of deflazacort (DFZ). In vitro studies were performed to evaluate cytochrome P450 (CYP)‐ and transporter‐mediated drug interaction potentials of 6β‐OH‐21‐desDFZ. Up to 50 µM, the highest soluble concentration in the test system, 6β‐OH‐21‐desDFZ weakly inhibited (IC50 > 50 µM) the enzyme activity of CYPs 1A2, 2B6, 2C8, 2C9, and 2D6, while moderately inhibiting CYP2C19 and CYP3A4 with IC50 values of approximately 50 and 35 μM, respectively. The inhibition was neither time‐dependent nor metabolism‐based. Incubation of up to 50 µM 6β‐OH‐21‐desDFZ with plated cryopreserved human hepatocytes for 48 h resulted in no meaningful concentration‐dependent induction of either mRNA levels or enzyme activity of CYP1A2, CYP2B6, or CYP3A4. In transporter inhibition assays, 6β‐OH‐21‐desDFZ, up to 50 µM, did not show interaction with human OAT1, OAT3, and OCT2 transporters. It weakly inhibited (IC50 > 50 µM) human MATE1, MATE2‐K, and OCT1 transporter activity, and moderately inhibited human MDR1, OATP1B1, and OATP1B3 transporter activity with IC50 values of 19.81 μM, 37.62 μM, and 42.22 μM, respectively. 14C‐6β‐OH‐21‐desDFZ was biosynthesized using bacterial biotransformation and the subsequent study showed that 6β‐OH‐21‐desDFZ was not a substrate for human BCRP, MDR1, MATE1, MATE2‐K, OAT1, OATP1B1, OATP1B3, and OCT2 transporters, but appeared to be an in vitro substrate for the human OAT3 uptake transporter. At plasma concentrations of 6β‐OH‐21‐desDFZ seen in the clinic, CYP‐ and transporter‐mediated drug–drug interactions are not expected following administration of a therapeutic dose of DFZ in Duchenne muscular dystrophy (DMD) patients.

Abstract Turtles are in decline worldwide, and the magnitude and recent acceleration of population declines requires immediate action to inform conservation and management plans. Long‐term studies of population trends and characteristics covering multiple populations across a range of environmental contexts are needed to guide the most effective management decisions, yet such studies are uncommon. Eastern box turtle (Terrapene carolina carolina) populations have declined and require conservation action throughout much of their range. We assessed sources of variation and temporal trends in T. c. carolina population characteristics from 39 sites spanning four ecoregions in North Carolina using capture–mark–recapture. Surprisingly, there was no evidence of population decline at any site over a ten‐year period (2008–2017). Population densities ranged from 0.2 to 6.0 turtles per hectare, decreasing with more urban development and increasing with more wetland habitats in the surrounding landscape. Populations varied in demographic structure but had similar sex ratios and more adults than immature turtles in each ecoregion even after adjusting for variation in encounter probability among groups and body sizes. Survivorship was similar among life stages and sexes and only weakly related to body size. After adjusting for emigration, annual survival probability ranged from 90.7% to 96.8% for the various demographic groups and body sizes. Growth rates decreased with increasing body size, with rates ranging from approximately 15‐mm carapace length per year in the smallest individuals to near zero in the largest individuals. No aspect of population demographic structure or vital rates was related to surrounding landscape context. Population trends and characteristics were consistent among ecoregions, suggesting no need for region‐specific conservation or management with respect to the population characteristics examined. However, given the high site‐specific variability in nearly all estimated parameters, managers would benefit from targeting local threats such as urban land development and wetland destruction to ensure local population viability. The population characteristics reported here can serve as a useful baseline to compare population trends at these sites as monitoring continues. Our approach could be a useful model for other regions to follow in developing monitoring programs for this and other imperiled turtles.

Background Coronary artery disease (CAD) is increasing among young adults. We aimed to describe the cardiovascular risk factors and long‐term prognosis of premature CAD. Methods and Results Using the Duke Databank for Cardiovascular Disease, we evaluated 3655 patients admitted between 1995 and 2013 with a first diagnosis of obstructive CAD before the age of 50 years. Major adverse cardiovascular events (MACEs), defined as the composite of death, myocardial infarction, stroke, or revascularization, were ascertained for up to 10 years. Cox proportional hazard regression models were used to assess associations with the rate of first recurrent event, and negative binomial log‐linear regression was used for rate of multiple event recurrences. Past or current smoking was the most frequent cardiovascular factor (60.8%), followed by hypertension (52.8%) and family history of CAD (39.8%). Within a 10‐year follow‐up, 52.9% of patients had at least 1 MACE, 18.6% had at least 2 recurrent MACEs, and 7.9% had at least 3 recurrent MACEs, with death occurring in 20.9% of patients. Across follow‐up, 31.7% to 37.2% of patients continued smoking, 81.7% to 89.3% had low‐density lipoprotein cholesterol levels beyond the goal of 70 mg/dL, and 16% had new‐onset diabetes mellitus. Female sex, diabetes mellitus, chronic kidney disease, multivessel disease, and chronic inflammatory disease were factors associated with recurrent MACEs. Conclusions Premature CAD is an aggressive disease with frequent ischemic recurrences and premature death. Individuals with premature CAD have a high proportion of modifiable cardiovascular risk factors, but failure to control them is frequently observed.

Abstract Wildlife crime in protected areas remains a major challenge to conservation. However, little is known about the role of local communities in providing information on illegal activities to help improve law enforcement efforts in protected areas. As an initial exploration of this complex topic, we aimed to understand the perceptions of law enforcement authorities working directly with local communities on the conditions under which local people provide information to park rangers, using Murchison Falls Protected Area in Uganda as a case study. We used semi‐structured interviews and questionnaires to understand the perceptions of staff from the Uganda Wildlife Authority and nongovernmental organizations. There was consensus among participants that people who provide information are those who have trusted relationships with rangers; interact regularly with community outreach rangers (either formally through community programs or informal socializing); and believe that the protected area benefits them and their community. All respondents believed that information provided by local people can enable the success of wildlife crime investigations, but that associated ethical issues must be addressed. This study indicates that engaging communities in protected area conservation is crucial for law enforcement efforts to be effective in addressing wildlife crime.

Abstract It has been previously reported that ursodeoxycholic acid (UDCA), a therapeutic bile acid, reduced risk for advanced colorectal adenoma in men but not women. Interactions between the gut microbiome and fecal bile acid composition as a factor in colorectal cancer neoplasia have been postulated but evidence is limited to small cohorts and animal studies. Using banked stool samples collected as part of a phase III randomized clinical trial of UDCA for the prevention of colorectal adenomatous polyps, we compared change in the microbiome composition after a 3‐year intervention in a subset of participants randomized to oral UDCA at 8‐10 mg/kg of body weight per day (n = 198) or placebo (n = 203). Study participants randomized to UDCA experienced compositional changes in their microbiome that were statistically more similar to other individuals in the UDCA arm than to those in the placebo arm. This reflected a UDCA‐associated shift in microbial community composition (P 0.05). These UDCA‐associated shifts in microbial community distance metrics from baseline to end‐of‐study were not associated with risk of any or advanced adenoma (all P > 0.05) in men or women. Separate analyses of microbial networks revealed an overrepresentation of Faecalibacterium prausnitzii in the post‐UDCA arm and an inverse relationship between F prausnitzii and Ruminococcus gnavus. In men who received UDCA, the overrepresentation of F prausnitzii and underrepresentation of R gnavus were more prominent in those with no adenoma recurrence at follow‐up compared to men with recurrence. This relationship was not observed in women. Daily UDCA use modestly influences the relative abundance of microbial species in stool and affects the microbial network composition with suggestive evidence for sex‐specific effects of UDCA on stool microbial community composition as a modifier of colorectal adenoma risk.

Abstract Loss of habitats or ecosystems arising from development projects (e.g., infrastructure, resource extraction, urban expansion) are frequently addressed through biodiversity offsetting. As currently implemented, offsetting typically requires an outcome of “no net loss” of biodiversity, but only relative to a baseline trajectory of biodiversity decline. This type of “relative” no net loss entrenches ongoing biodiversity loss, and is misaligned with biodiversity targets that require “absolute” no net loss or “net gain.” Here, we review the limitations of biodiversity offsetting, and in response, propose a new framework for compensating for biodiversity losses from development in a way that is aligned explicitly with jurisdictional biodiversity targets. In the framework, targets for particular biodiversity features are achieved via one of three pathways: Net Gain, No Net Loss, or (rarely) Managed Net Loss. We outline how to set the type (“Maintenance” or “Improvement”) and amount of ecological compensation that is appropriate for proportionately contributing to the achievement of different targets. This framework advances ecological compensation beyond a reactive, ad‐hoc response, to ensuring alignment between actions addressing residual biodiversity losses and achievement of overarching targets for biodiversity conservation.

Summary Objective The Diet Satisfaction Questionnaire was developed to fill the need for a validated measure to evaluate satisfaction with weight‐management diets. This paper further develops the questionnaire, examining the factor structure of the original questionnaire, cross‐validating a revised version in a second sample and relating diet satisfaction to weight loss during a 1‐year trial. Methods The 45‐item Diet Satisfaction Questionnaire (DSat‐45) uses seven scales to assess characteristics that influence diet satisfaction: Healthy Lifestyle, Convenience, Cost, Family Dynamics, Preoccupation with Food, Negative Aspects, and Planning and Preparation. It was administered five times during a 1‐year weight‐loss trial (n = 186 women) and once as an online survey in a separate sample (n = 510 adults). Confirmatory factor analysis was used to assess and refine the DSat‐45 structure, and reliability and validity data were examined in both samples for the revised questionnaire, the DSat‐28. Associations were examined between both DSat questionnaires and weight loss in the trial. Results Internal consistency (reliability) was moderate for the DSat‐45. Confirmatory factor analysis showed improved fit for a five‐factor structure, resulting in the DSat‐28 that retained four of the original scales and a shortened fifth scale. This revised questionnaire was reliable in both samples. Weight loss across the year‐long trial was positively related to satisfaction with Healthy Lifestyle, Preoccupation with Food, and Planning and Preparation in both versions of the questionnaire. Conclusions Measures of reliability and validity were improved in the more concise DSat‐28 compared to the DSat‐45. This shorter measure should be used in future work to evaluate satisfaction with weight‐management diets.