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Abstract The rapid and repeatable characterization of individual morphology has advanced automated taxonomic classification. The most direct study of evolutionary processes is, however, not from taxonomic description, but rather of the evolution of the traits that comprise individuals and define species. Repeatable signatures of individual morphology are crucial for analysing the response to selection at scale, and thus tracking evolutionary trajectories through time and across species boundaries. Here, we introduce our 3DKMI—an open‐source MATLAB package designed for the study of morphology using three‐dimensional (3D) Krawtchouk moment invariants. The volumetric features derived from the 3D images remain stable under translation, scaling and rotation and, for an image of size 128 × 128 × 128 can be computed in less than 0.1 s. We applied our package as a case study on a collection of 300 X‐ray computed tomography scans of planktonic foraminifera specimens across five species to (1) assess the invariance of the features under different transformations and (2) analyse morphological differences among species based on the extracted characteristics. We show that 3DKMI has the capacity to efficiently and repeatedly characterize the signatures of individual morphology. In the future, we hope that the 3D feature extraction technique 3DKMI will be widely applied to digital collections to advance research in ecology and evolution.

Abstract Objective Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2‐item scale polygenic score with anxiety in MS. Methods Using a case–control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview‐diagnosed, and lifetime self‐report physician‐diagnosed. The polygenic score was computed for current anxiety symptoms using summary statistics from a previous genome‐wide association study and was tested using regression. Results A total of 71,343 individuals of European genetic ancestry were used: Canada (n = 334; 212 MS), UK Biobank (n = 70,431; 1,390 MS), and the USA (n = 578 MS). Meta‐analyses identified that in MS, each 1‐SD increase in the polygenic score was associated with ~50% increased odds of comorbid moderate anxious symptoms compared to those with less than moderate anxious symptoms (OR: 1.47, 95% CI: 1.09–1.99). We found a similar direction of effects in the other measures. MS had a similar anxiety genetic burden compared to people with anxiety as the index disease. Interpretation Higher genetic burden for anxiety was associated with significantly increased odds of moderate anxious symptoms in MS of European genetic ancestry which did not differ from those with anxiety and no comorbid immune disease. This study suggests a genetic basis for anxiety in MS.

Abstract Environmental change, particularly warming and eutrophication, can alter phenology in aquatic systems. Understanding controls on zooplankton phenology is important due to their central role in food webs. While patterns in zooplankton phenology have been well documented, we lack an understanding of how abiotic and biotic drivers influence lake zooplankton phenology during the summer. We examined the phenology of four common zooplankton taxa (Daphnia retrocurva, Skistodiaptomus oregonensis, Mesocyclops spp., Dreissenid veligers) in western Lake Erie during 1995–2022, a period with increasing eutrophication and Bythotrephes longimanus biomass. Many phenology metrics varied by 3 weeks or more from 1995 to 2022. The dominant controls of phenology were temperature and biotic factors, especially grazer‐defended phytoplankton (cyanobacteria and other colonial or filamentous taxa) and the invasive predator B. longimanus, which frequently interacted. Our results show that aspects of environmental change interact to shape zooplankton phenology, which can influence phytoplankton biomass and energy flow to higher trophic levels.

Abstract Ontogenetic changes in area use, habitat use, and trophic interactions play an important role in the ecology, demography, and ultimately population dynamics of many species. Assumed to be driven by shifting life‐history requirements, trophic niche shifts in white sharks (Carcharodon carcharias) are well documented, but the timing of the spatial niche shift that is hypothesized to occur with the trophic niche shift remains poorly understood. To document how fine‐scale area use varies as sharks age and the timing of the ontogenetic spatial shift of this top predator, we tracked individual white sharks tagged as young‐of‐the‐year or young juveniles over multiple years. Using data from juvenile white sharks detected over multiple years in a nursery habitat with a high‐density receiver array, we found no difference in area use with age. However, using a coast‐wide receiver array including nursery and adult habitat, we found the probability of detecting a juvenile white shark in nursery habitat decreased with age, with a concurrent increasing probability of detection in adult habitat. As the conservation and management of this species relies on understanding nursery habitat use and age‐related movements, data presented here address an important knowledge gap for the understudied juvenile to subadult life stages and the ontogenetic habitat shift of this species.

Abstract Hydrogels are extensively employed in healthcare due to their adaptable structures, high water content, and biocompatibility, with FDA‐approved applications ranging from spinal cord regeneration to local therapeutic delivery. However, clinical hydrogels encounter challenges related to inconsistent therapeutic exposure, unmodifiable release windows, and difficulties in subsurface polymer insertion. Addressing these issues, we engineered injectable, biocompatible hydrogels as a local therapeutic depot, utilizing poly(ethylene glycol) (PEG)‐based hydrogels functionalized with bioorthogonal SPAAC handles for network polymerization and functionalization. Our hydrogel solutions polymerize in situ in a temperature‐sensitive manner, persist in tissue, and facilitate the delivery of bioactive therapeutics in subsurface locations. Demonstrating the efficacy of our approach, recombinant anti‐CD47 monoclonal antibodies, when incorporated into subsurface‐injected hydrogel solutions, exhibited cytotoxic activity against infiltrative high‐grade glioma xenografts in the rodent brain. To enhance the gel's versatility, recombinant protein cargos can undergo site‐specific modification with hydrolysable “azidoester” adapters, allowing for user‐defined release profiles from the hydrogel. Hydrogel‐generated gradients of murine CXCL10, linked to intratumorally injected hydrogel solutions via azidoester linkers, resulted in significant recruitment of CD8+ T‐cells and the attenuation of tumor growth in a “cold” syngeneic melanoma model. This study highlights a highly customizable, hydrogel‐based delivery system for local protein therapeutic administration to meet diverse clinical needs.

Societal Impact Statement Cultivation of strawberry plants in urban production systems, whether in green open‐air spaces or under some form of protected horticulture such as vertical farming, has demonstrated to be challenging to new farmers and businesses. Commercial strawberry producers have an advanced understanding of strawberry plant physiology, enabling them to grow the crop successfully and profitably. Lack of knowledge exchange between commercial growers and new urban farmers seems to result in the abandonment of strawberries as crop of choice in urban systems. This review will confront the specific plant science challenges urban growers need to address to incorporate this nutritional crop into their revolutionary urban growing systems, whilst achieving good quality produce with high yields. Summary To ensure a sustainable future of farming, urban horticulture (UH) will need to be a key part of our everyday life. There are increasing demands for higher productivity and more locally produced food, even close to densely populated urban areas, to address environmental pressures and accelerate the resilience of modern food systems. UH is a broad term and can include numerous cultivation methods; rooftop gardens, public spaces, vertical walls, indoor vertical farms, as well as an array of crops including, salads, soft fruits and trees. Crops such as strawberries are expected to soon make a significant contribution to UH. Urban strawberry production promises all‐year round fruit availability, reduced reliance on imports, increased self‐sufficiency, lower food miles, a supply of high‐quality fresh fruits from hyper‐local spaces, increased employment opportunities, welfare benefits and an opportunity to promote a sense of community. Strawberry is a complex perennial crop with agronomical challenges, which requires specialist knowledge that is not always available to new urban farmers. Achieving an urban version of a strawberry field will require knowledge exchange between the commercial rural strawberry producers and the newly entered urban growers. Plant physiology, management of plant pathogens, choice of propagation material, fertigation, pollination and environmental requirements are the most common challenges for urban strawberry production. This review aims to consolidate the common bottleneck challenges of UH for new urban strawberry facilities.

Abstract The incredibly complex soil microbial communities at small scales make their analysis and identification of reasons for the observed structures challenging. Microbial community structure is mainly a result of the inoculum (dispersal), the selective advantages of those organisms under the habitat‐based environmental attributes, and the ability of those colonizers to sustain themselves over time. Since soil is protective, and its microbial inhabitants have long adapted to varied soil conditions, significant portions of the soil microbial community structure are likely stable. Hence, a substantial portion of the community will not correlate to often measured soil attributes. We suggest that the drivers be ranked on the basis of their importance to the fundamental needs of the microbes: (i) those that supply energy, i.e., organic carbon and electron acceptors; (ii) environmental effectors or stressors, i.e., pH, salt, drought, and toxic chemicals; (iii) macro‐organism associations, i.e., plants and their seasonality, animals and their fecal matter, and soil fauna; and (iv) nutrients, in order, N, P, and probably of lesser importance, other micronutrients, and metals. The relevance of drivers also varies with spatial and time scales, for example, aggregate to field to regional, and persistent to dynamic populations to transcripts, and with the extent of phylogenetic difference, hence phenotypic differences in organismal groups. We present a summary matrix to provide guidance on which drivers are important for particular studies, with special emphasis on a wide range of spatial and temporal scales, and illustrate this with genomic and population (rRNA gene) data from selected studies.

Background Intracranial hemorrhage is a critical finding on computed tomography (CT) of the head. This study compared the accuracy of an artificial intelligence (AI) model (Annalise Enterprise CTB Triage Trauma) to consensus neuroradiologist interpretations in detecting 4 hemorrhage subtypes: acute subdural/epidural hematoma, acute subarachnoid hemorrhage, intra‐axial hemorrhage, and intraventricular hemorrhage. Methods A retrospective stand‐alone performance assessment was conducted on data sets of cases of noncontrast CT of the head acquired between 2016 and 2022 at 5 hospitals in the United States for each hemorrhage subtype. The cases were obtained from patients aged ≥18 years. The positive cases were selected on the basis of the original clinical reports using natural language processing and manual confirmation. The negative cases were selected by taking the next negative case acquired from the same CT scanner after positive cases. Each case was interpreted independently by up to 3 neuroradiologists to establish consensus interpretations. Each case was then interpreted by the AI model for the presence of the relevant hemorrhage subtype. The neuroradiologists were provided with the entire CT study. The AI model separately received thin (≤1.5 mm) and thick (>1.5 and ≤5 mm) axial series as available. Results The 4 cohorts included 571 cases of acute subdural/epidural hematoma, 310 cases of acute subarachnoid hemorrhage, 926 cases of intra‐axial hemorrhage, and 199 cases of intraventricular hemorrhage. The AI model identified acute subdural/epidural hematoma with area under the curve of 0.973 (95% CI, 0.958–0.984) on thin series and 0.942 (95% CI, 0.921–0.959) on thick series; acute subarachnoid hemorrhage with area under the curve 0.993 (95% CI, 0.984–0.998) on thin series and 0.966 (95% CI, 0.945–0.983) on thick series; intraaxial hemorrhage with area under the curve of 0.969 (95% CI, 0.956–0.980) on thin series and 0.966 (95% CI, 0.953–0.976) on thick series; and intraventricular hemorrhage with area under the curve of 0.987 (95% CI, 0.969–0.997) on thin series and 0.983 (95% CI, 0.968–0.994) on thick series. Each finding had at least 1 operating point with sensitivity and specificity >80%. Conclusion The assessed AI model accurately identified intracranial hemorrhage subtypes in this CT data set. Its use could assist the clinical workflow, especially through enabling triage of abnormal CTs.

Abstract Purpose Real world evidence is crucial to understanding the diffusion of new oncologic therapies, monitoring cancer outcomes, and detecting unexpected toxicities. In practice, real world evidence is challenging to collect rapidly and comprehensively, often requiring expensive and time‐consuming manual case‐finding and annotation of clinical text. In this Review, we summarise recent developments in the use of artificial intelligence to collect and analyze real world evidence in oncology. Methods We performed a narrative review of the major current trends and recent literature in artificial intelligence applications in oncology. Results Artificial intelligence (AI) approaches are increasingly used to efficiently phenotype patients and tumors at large scale. These tools also may provide novel biological insights and improve risk prediction through multimodal integration of radiographic, pathological, and genomic datasets. Custom language processing pipelines and large language models hold great promise for clinical prediction and phenotyping. Conclusions Despite rapid advances, continued progress in computation, generalizability, interpretability, and reliability as well as prospective validation are needed to integrate AI approaches into routine clinical care and real‐time monitoring of novel therapies.

Abstract The necessity for sustainable agricultural practices has propelled a renewed interest in legumes such as faba bean (Vicia faba L.) as agents to help deliver increased diversity to cropped systems and provide an organic source of nitrogen (N). However, the increased cultivation of faba beans has proven recalcitrant worldwide as a result of low yields. So, it is hoped that increased and more stable yields would improve the commercial success of the crop and so the likelihood of cultivation. Enhancing biological N fixation (BNF) in faba beans holds promise not only to enhance and stabilize yields but also to increase residual N available to subsequent cereal crops grown on the same field. In this review, we cover recent progress in enhancing BNF in faba beans. Specifically, rhizobial inoculation and the optimization of fertilizer input and cropping systems have received the greatest attention in the literature. We also suggest directions for future research on the subject. In the short term, modification of crop management practices such as fertilizer and biochar input may offer the benefits of enhanced BNF. In the long term, natural variation in rhizobial strains and faba bean genotypes can be harnessed. Strategies must be optimized on a local scale to realize the greatest benefits. Future research must measure the most useful parameters and consider the economic cost of strategies alongside the advantages of enhanced BNF.

Abstract Understanding changes in the hazard component of climate risk is important to inform societal resilience planning in a changing climate. Here, we examine local changes in wind speed, rainfall, and flooding related to tropical cyclones (TCs) and compare them across statistical and dynamical modeling approaches. Our focus region is the Delaware River Basin, located in the northeastern United States. We pair event‐based downscaling with large ensemble climate model information to capture the details of extreme TC wind, rain, and flooding, and their likelihood, in a changing climate. We identify local TCs in the Community Earth System Model 2 Large Ensemble (CESM2‐LENS). We find fewer TCs in the future, but these future storms have higher wind speeds and are wetter. We also find that TCs produce heavier 3‐day precipitation distributions than all other summertime weather events, with TCs constituting a larger percentage of the upper tail of the full precipitation distribution. With this information, we identify a small collection of 200‐year return events and compare the resulting TC rain and wind across dynamical and statistical downscaling methods. We find that dynamical downscaling produces peak rain rates far higher than CESM or the statistical downscaling method. It can also produce quite different future changes in precipitation totals for the small set of events considered here. This leads to vastly different flood responses. Overall, our results highlight the need to interpret future changes of event‐based simulations in the context of downscaling method limitations.

Abstract Background Aging is associated with changes in body composition, and preventing loss of muscle mass and accumulation of excess adipose tissue in middle‐aged adults may reduce age‐related conditions at older ages. Dietary intake is one lifestyle factor shown to improve or maintain body composition. However, few studies have examined the Healthy Eating Index2015 (HEI2015), a measure of diet quality, and the association with body composition in adult men and women. Methods Participant data (n = 3017) from the Coronary Artery Risk Development in Young Adults (CARDIA) study were used to examine the associations of the HEI2015 with body composition measures at Year 25 (Y25), including (1) 25 year‐change in weight, body mass index (BMI), and waist circumference and (2) a computed tomography (CT) scan at Y25 measured muscle mass, muscle quality (better quality = less lipid within the muscle), and adipose tissue depots visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and adipose within skeletal muscle (intermuscular adipose tissue; IMAT). Dietary intake was assessed by a diet history three times over 20 years, at years 0, 7, and 20. HEI2015, averaged over three exams, was created and categorized into quintiles. Multiple regression analysis evaluated the associations of body composition stratified across quintiles of HEI2015 adjusted for demographic characteristics, energy intake, lifestyle factors, and baseline anthropometric measures as appropriate. Race–sex interaction was tested (Pinteraction > 0.30). Results Over 25 years of follow‐up, averaged HEI2015 was significantly and inversely associated with weight gain (Quintile 1 (Q1) 37.3 lb vs. 32.9 in Q5; Ptrend = 0.01), change in BMI (Q1 5.8 kg/m2 vs. 5.0 in Q5; Ptrend = 0.005), and change in waist circumference (Q1 17.5 cm vs. 15.2 cm in Q5; Ptrend

Abstract The marginal Fisher information (MFI) metric is used to design waveforms for the sake of informationally optimal adaptive‐on‐transmit radar operation. A framework for MFI waveform design is developed and the Polyphase‐Coded FM (PCFM) waveform model is utilised to produce a constant‐modulus, spectrally contained signal amenable to transmission with high‐power amplifiers. The efficacy of the MFI waveform design and minimum mean square error (MMSE) estimation is experimentally demonstrated and extended into an adaptive and dynamic sensing paradigm. The radar transmit waveform is optimised to maximise the Fisher information with respect to the range profile. Upon observing new information from radar echoes, the iterative MMSE (iMMSE) estimator then minimises the estimation error variance according to prior observations. Sequential information maximisation (via waveform design) and error minimisation (via iMMSE) tends towards the Cramér–Rao lower bound (CRLB) with additional measurements improving radar resolution and accuracy. These concepts maximise the information extracted by a radar operating in a congested spectrum where the available bandwidth is limited.

Abstract The emergence and rapid spread of antimicrobial resistance is of global public health concern. The gut microbiota harboring diverse commensal and opportunistic bacteria that can acquire resistance via horizontal and vertical gene transfers is considered an important reservoir and sink of antibiotic resistance genes (ARGs). In this review, we describe the reservoirs of gut ARGs and their dynamics in both animals and humans, use the One Health perspective to track the transmission of ARG‐containing bacteria between humans, animals, and the environment, and assess the impact of antimicrobial resistance on human health and socioeconomic development. The gut resistome can evolve in an environment subject to various selective pressures, including antibiotic administration and environmental and lifestyle factors (e.g., diet, age, gender, and living conditions), and interventions through probiotics. Strategies to reduce the abundance of clinically relevant antibiotic‐resistant bacteria and their resistance determinants in various environmental niches are needed to ensure the mitigation of acquired antibiotic resistance. With the help of effective measures taken at the national, local, personal, and intestinal management, it will also result in preventing or minimizing the spread of infectious diseases. This review aims to improve our understanding of the correlations between intestinal microbiota and antimicrobial resistance and provide a basis for the development of management strategies to mitigate the antimicrobial resistance crisis.

Abstract Energy absorption and flow through a nest is an important aspect of embryonic development in many reptile species including turtles. To date, few studies have explicitly attempted to quantify the energy flow through turtle nests, opting instead for the simplified approach offered by temperature index models. However, the quantification of the energy can provide an explicit abiotic link that can link biological models to biometeorological and ecohydrological processes and models. We investigated the energy flow through turtle nests occupying different bedrock morphologies within a Canadian Shield Rock Barren landscape, in Ontario, Canada. The taxons studied were Spotted Turtle (Clemmys guttata), Midland Painted Turtle (Chrysemys picta marginata), and Blanding's Turtle (Emydoidea blandingii). Nest temperature and soil moisture were measured in 2018 and 2019 using sensors placed in the soil adjacent to 12 turtle nest cavities. Three main rock morphologies were identified for each nest location, Crevice, Ledge, and Flat types, that are in order of decreasing bedrock percentage contact with the nest site. Ground heat flux and change in heat storage were determined using the calorimetric method for each nest, while the direction of energy flux between the atmosphere and the underlying rock was also determined. The Crevice nest morphology experienced the lowest ground heat flux on average (1.56 × 10−1 W m−2) and lowest cumulative heat storage (230 MJ) compared to the Flat (440 MJ) and Ledge (331 MJ) nests. However, over the diurnal cycle, large heat gains by Flat nests were mostly balanced out by nighttime heat losses. While Crevice nests saw the lowest daily heat storage gains, they experienced much lower heat losses over the evening period compared to the other nest types. Furthermore, we found that 59% of the energy is directed from the underlying bedrock into the Crevice nest, highlighting the importance of the bedrock in controlling thermal dynamics in the turtle nesting habitat. The lower variability in energy parameters for Crevice nest types can be attributed to higher amounts of nest‐to‐bedrock contact, compared to the flat nest types. Our results indicate that Crevice morphology may be ideal for turtles nesting at their northern limits because minimal heat loss during the evening can result in a more stable thermal incubation environment. Future conservation and habitat restoration efforts should consider the importance of bedrock morphology and prioritize the protection of Crevice nest sites. Furthermore, this work highlights important opportunities for potential interdisciplinary work between ecologists, climatologists, biologists, and hydrologists, specifically the integration of ecohydrological and biological models. This work also underscores the potential uncertainty of climate change impacts on turtle egg hatching success and nest sex ratios.

Abstract Stratospheric Aerosol Injection (SAI) is a proposed method of climate intervention aiming to reduce the impacts of human‐induced global warming by reflecting a portion of incoming solar radiation. Many studies have demonstrated that SAI would successfully reduce global‐mean surface air temperatures; however the vast array of model scenarios and strategies result in a diverse range of climate impacts. Here we compare two SAI strategies—a quasi‐ equatorial injection and a multi‐latitude off‐equatorial injection—simulated with the UK Earth System Model (UKESM1), both aiming to reduce the global‐mean surface temperature from that of a high‐end emissions scenario to that of a moderate emissions scenario. We compare changes in the surface and stratospheric climate under each strategy to determine how the climate response depends on the injection location. In agreement with previous studies, an equatorial injection results in a tropospheric overcooling in the tropics and a residual warming in the polar regions, with substantial changes to stratospheric temperatures, water vapor and circulation. Previous comparisons of equatorial versus off‐equatorial injection strategies are limited to two studies using different versions of the Community Earth System Model. Our study evaluates how the climate responds in UKESM1 under these injection strategies. Our results are broadly consistent with previous findings, concluding that an off‐equatorial injection strategy can minimize regional surface temperature and precipitation changes relative to the target. We also present more in‐depth analysis of the associated changes in Hadley Circulation and regional temperature changes, and call for a new series of inter‐model SAI comparisons using an off‐equatorial strategy.

Cardiogenic shock continues to carry a high mortality rate despite contemporary care, with no breakthrough therapies shown to improve survival over the past few decades. It is a time‐sensitive condition that commonly results in cardiovascular complications and multisystem organ failure, necessitating multidisciplinary expertise. Managing patients with cardiogenic shock remains challenging even in well‐resourced settings, and an important subgroup of patients may require cardiac replacement therapy. As a result, the idea of leveraging the collective cognitive and procedural proficiencies of multiple providers in a collaborative, team‐based approach to care (the “shock team”) has been advocated by professional societies and implemented at select high‐volume clinical centers. A slowly maturing evidence base has suggested that cardiogenic shock teams may improve patient outcomes. Although several registries exist that are beginning to inform care, particularly around therapeutic strategies of pharmacologic and mechanical circulatory support, none of these are currently focused on the shock team approach, multispecialty partnership, education, or process improvement. We propose the creation of a Cardiogenic Shock Team Collaborative—akin to the successful Pulmonary Embolism Response Team Consortium—with a goal to promote sharing of care protocols, education of stakeholders, and discovery of how process and performance may influence patient outcomes, quality, resource consumption, and costs of care.

Abstract Landscape modification is a major threat to carnivores worldwide, but modified landscapes can also provide important habitat for these species, as protected areas alone are insufficient. Understanding how carnivores use modified landscapes, such as production forests, can inform management strategies to improve the value of these landscapes to carnivores. Little is known about habitat selection by marsupial carnivores in production forests, where they occupy a similar ecological niche to their more well‐studied eutherian counterparts. We used GPS tracking, Hidden Markov Models, and Manly's selection ratios to identify the habitat selected in three behavioral states by the largest marsupial carnivore, the Tasmanian devil (Sarcophilus harrisii), in a timber plantation‐dominated landscape. Behavioral states were approximated as: state 1, resting or feeding at a carcass; state 2, foraging; and state 3, travel. Devils did not show preferences for any of native forest, native grassland, and plantation in any behavioral state. Within plantations, devils preferred a plantation age of 4–7 years (selection ratio [wi] = 1.52). Devils preferred roads (state 1: wi = 2.71, state 2: wi = 2.48, state 3: wi = 2.97) and plantation edges (state 1: wi = 2.38, state 2: wi = 2.24, state 3: wi = 2.78) in all behavioral states, and moved faster on roads and edges than away from them. Together, our results indicate devils use road and edges for foraging (scavenging and hunting) and travel. No measured habitat variables influenced devil home range size. To support devils in plantation landscapes, we recommend maintaining a heterogeneous landscape of different plantation ages and native remnants and reducing the risk of vehicle collisions by minimizing forestry traffic at night. Tasmanian devils share similar adaptable traits to generalist eutherian carnivore species in their use of modified landscapes. Plantations can provide valuable habitat for this and other threatened predator species.

Abstract Background A treatment of chronic kidney disease (CKD)‐associated anemia in cats is needed. SB‐001 is an adeno‐associated virus‐vectored (AAV)‐based gene therapeutic agent that is administered intramuscularly, causing the expression of feline erythropoietin. Hypothesis/Objective We hypothesized that SB‐001 injection would lead to a sustained increase in PCV in cats with CKD‐associated anemia. Animals Twenty‐three cats with International Renal Interest Society (IRIS) Stage 2 to 4 CKD‐associated anemia were enrolled at 4 veterinary clinics. Methods In a prospective clinical trial, cats were treated with 1 of 3 regimens of SB‐001 (Lo 1.2 × 109 genome copies [GCs] on Day 0; Lo ± Hi [supplemental 2nd dose of 3.65 × 109 GC on Day 42]; Hi 3.65 × 109 GC IM on Day 0) and followed for 70 days. Results A response to SB‐001 at any time between Day 28 and Day 70 was seen in 86% (95% confidence interval 65, 97%) of all cats. There was a significant (P

Abstract Background Since 2005, highly pathogenic avian influenza A H5N1 viruses have spread from Asia worldwide, infecting poultry, humans and wild birds. Subsequently, global interest in avian influenza (AI) surveillance increased. Objectives Mongolia presents an opportunity to study viruses in wild birds because the country has very low densities of domestic poultry and supports large concentrations of migratory water birds. Methods We conducted AI surveillance in Mongolia over two time periods, 2009–2013 and 2016–2018, utilizing environmental fecal sampling. Fresh fecal samples were collected from water bird congregation sites. Hemagglutinin (HA) and neuraminidase (NA) subtypes of positive samples were identified through viral isolation or molecular assays, with pathogenicity determined by HA subtype or sequencing the HA cleavage site. Results A total of 10,222 samples were collected. Of these, 7,025 fecal samples were collected from 2009 to 2013, and 3,197 fecal samples were collected from 2016 to 2018. Testing revealed 175 (1.7%) positive samples for low‐pathogenicity influenza A, including 118 samples from 2009 to 2013 (1.7%) and 57 samples from 2016 to 2018 (1.8%). HA and NA subtyping of all positives identified 11 subtypes of HA and nine subtypes of NA in 29 different combinations. Within periods, viruses were detected more frequently during the fall season than in the early summer. Conclusion Mongolia's critical wild bird habitat is positioned as a crossroad of multiple migratory flyways. Our work demonstrates the feasibility of using an affordable environmental fecal sampling approach for AI surveillance and contributes to understanding the prevalence and ecology of low‐pathogenicity avian influenza viruses in this important location, where birds from multiple flyways mix.

Societal Impact Statement Given the rapidly increasing drought and temperature stresses associated with climate change, innovative approaches for food security are imperative. One understudied opportunity is using feral crops—plants that have escaped and persisted without cultivation—as a source of genetic diversity, which could build resilience in domesticated conspecifics. In some cases, however, feral plants vigorously compete with crops as weeds, challenging food security. By bridging historically siloed ecological, agronomic, and evolutionary lines of inquiry into feral crops, there is the opportunity to improve food security and understand this relatively understudied anthropogenic phenomenon. Summary The phenomenon of feral crops, that is, free‐living populations that have established outside cultivation, is understudied. Some researchers focus on the negative consequences of domestication, whereas others assert that feral populations may serve as useful pools of genetic diversity for future crop improvement. Although research on feral crops and the process of feralization has advanced rapidly in the last two decades, generalizable insights have been limited by a lack of comparative research across crop species and other factors. To improve international coordination of research on this topic, we summarize the current state of feralization research and chart a course for future study by consolidating outstanding questions in the field. These questions, which emerged from the colloquium “Darwins' reversals: What we now know about Feralization and Crop Wild Relatives” at the BOTANY 2021 conference, fall into seven categories that span both basic and applied research: (1) definitions and drivers of ferality, (2) genetic architecture and pathway, (3) evolutionary history and biogeography, (4) agronomy and breeding, (5) fundamental and applied ecology, (6) collecting and conservation, and (7) taxonomy and best practices. These questions serve as a basis for ferality researchers to coordinate research in these areas, potentially resulting in major contributions to food security in the face of climate change.

Abstract Aim The aim of study was to investigate whether depression and anxiety symptoms and illness perception prior to hematopoietic stem cell transplantation (HSCT) predict health related quality of life (HRQOL) at Day 100 and 1 year following HSCT. Methods A total of 205 patients who underwent HSCT (N = 127 autologous transplants, N = 78 allogeneic transplants) were included in this prospective study. Baseline assessment was assessed prior to transplantation and post HSCT data were collected at Day 100 and 1 year. At baseline we assessed depressive symptoms (Patient Health Questionnaire‐9), anxiety symptoms (Generalized Anxiety Disorder‐7), illness perception (Brief Illness Perception Questionnaire), and HRQOL (Functional Assessment of Cancer Therapy‐BMT). Results Patients who expressed a greater level of concern about the severity, course, and ability to exert control over one's illness (i.e., illness perception) and who reported a greater level of depression and anxiety symptoms prior to HSCT reported lower HRQOL at both Day 100 and 1 year posttransplant, with a similar degree of association observed at the two follow‐up time points. Conclusions Our findings suggest that pretransplant perceptions about their illness and negative mood are significant predictors of HRQOL following HSCT. Illness perception, depression, and anxiety are potentially modifiable risk factors for less than optimal outcome after HCSCT and intervention strategies should be explored.

Abstract Objective Intranasal medications have been proposed as adjuncts to out‐of‐hospital cardiac arrest (OHCA) care. We sought to quantify the effects of intranasal medication administration (INMA) in OHCA workflows. Methods We conducted separate randomized OHCA simulation trials with lay rescuers (LRs) and first responders (FRs). Participants were randomized to groups performing hands‐only cardiopulmonary resuscitation (CPR)/automated external defibrillator with or without INMA during the second analysis phase. Time to compression following the second shock (CPR2) was the primary outcome and compression quality (chest compression rate (CCR) and fraction (CCF)) was the secondary outcome. We fit linear regression models adjusted for CPR training in the LR group and service years in the FR group. Results Among LRs, INMA was associated with a significant increase in CPR2 (mean diff. 44.1 s, 95% CI: 14.9, 73.3), which persisted after adjustment (p = 0.005). We observed a significant decrease in CCR (INMA 95.1 compressions per min (cpm) vs control 104.2 cpm, mean diff. −9.1 cpm, 95% CI −16.6, −1.6) and CCF (INMA 62.4% vs control 69.8%, mean diff. −7.5%, 95% CI −12.0, −2.9). Among FRs, we found no significant CPR2 delays (mean diff. −2.1 s, 95% CI −15.9, 11.7), which persisted after adjustment (p = 0.704), or difference in quality (CCR INMA 115.5 cpm vs control 120.8 cpm, mean diff. −5.3 cpm, 95% CI −12.6, 2.0; CCF INMA 79.6% vs control 81.2% mean diff. −1.6%, 95% CI −7.4, 4.3%) Conclusions INMA in LR resuscitation was associated with diminished resuscitation performance. INMA by FR did not impede key times or quality.

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.

Background Every year the American Heart Association's Resuscitation Science Symposium (ReSS) brings together a community of international resuscitation science researchers focused on advancing cardiac arrest care. Methods and Results The American Heart Association's ReSS was held in Chicago, Illinois from November 4th to 6th, 2022. This annual narrative review summarizes ReSS programming, including awards, special sessions and scientific content organized by theme and plenary session. Conclusions By exploring both the science of resuscitation and important related topics including survivorship, disparities, and community‐focused programs, this meeting provided important resuscitation updates.

Abstract Cancer therapy continues to be plagued by modest therapeutic advances. This is particularly evident in glioblastoma multiforme (GBM) wherein treatment failures are attributed to intratumoral heterogeneity (ITH), a dynamic process of cell state transitions or plasticity. To address ITH, we introduce the concept of cell state‐directed (CSD) therapy through a quantitative systems pharmacology model of temozolomide (TMZ), a cornerstone of GBM drug therapy. The model consisting of multiple modules incorporated an epigenetic‐based gene transcription‐translation module that enabled CSD therapy. Numerous model simulations were conducted to demonstrate the potential impact of CSD therapy on TMZ activity. The simulations included those based on global sensitivity analyses to identify fragile nodes – MDM2 and XIAP – in the network, and also how an epigenetic modifier (birabresib) could overcome a mechanism of TMZ resistance. The positive results of CSD therapy on TMZ activity supports continued efforts to develop CSD therapy as a new anticancer approach.

Introduction Previous studies did not show a difference in terms of safety and efficacy among first‐line stent retriever (SR), contact aspiration (CA), or combined techniques for proximal large vessel occlusion strokes. However, the optimal reperfusion therapy in patients with primary distal medium vessel occlusion (DMVO) strokes is uncertain. We aimed to compare the clinical and procedural outcomes among first‐line SR, CA and combined techniques in patients with primary DMVO. Methods This is a retrospective analysis of a prospectively maintained database from 14 comprehensive stroke centers in the US and Europe. Patients were included if they had a primary DMVO stroke due to MCA‐M3/M4, ACA‐A1/A2‐3, or PCA‐P1/P2‐3 and underwent mechanical thrombectomy with first‐line SR, CA, or combined technique. The primary outcome was FPE defined as eTICI 2c/3 on the first pass. Secondary outcomes included mFPE defined as eTICI 2b/3 on the first pass, successful reperfusion defined as eTICI 2b/3 at the end of the procedure. Clinical outcomes included 90‐day mRS0‐1 and 90‐day mRS0‐2. Safety measures included procedural complications, symptomatic intracranial hemorrhage (sICH), and 90‐day mortality. The secondary analysis aimed to identify the procedural and clinical outcomes in 3 matched cohorts: (SR vs. CA), (SR vs. combined technique), and (CA vs. combined technique). Results A total of 365 patients were eligible for analysis; 38.1% were female, with a mean age of 69.3 years and a median NIHSS score of 11 [7‐18]. The first‐line SR group consisted of n=74 (20.3%), CA group n=142 (38.9%), and combined technique group n=149 (40.8%). Patients with first‐line SR or combined technique had a lower median NIHSS score, less frequent MCA‐M3 segment occlusion, and less usage of the rescue strategy compared to those with first‐line CA, P

Abstract Climate change increases the frequency and intensity of extreme precipitation, which in combination with rising population enhances exposure to major floods. An improved understanding of the atmospheric processes that cause extreme precipitation events would help to advance predictions and projections of such events. To date, such analyses have typically been performed rather unsystematically and over limited areas (e.g., the U.S.) which has resulted in contradictory findings. Here we present the Multi‐Object Analysis of Atmospheric Phenomenon algorithm that uses a set of 12 common atmospheric variables to identify and track tropical and extra‐tropical cyclones, cut‐off lows, frontal zones, anticyclones, atmospheric rivers (ARs), jets, mesoscale convective systems (MCSs), and equatorial waves. We apply the algorithm to global historical data between 2001–2020 and associate phenomena with hourly and daily satellite‐derived extreme precipitation estimates in major climate regions. We find that MCSs produce the vast majority of extreme precipitation in the tropics and some mid‐latitude land regions, while extreme precipitation in mid and high‐latitude ocean and coastal regions are dominated by cyclones and ARs. Importantly, most extreme precipitation events are associated with phenomena interacting across scales that intensify precipitation. These interactions are a function of the intensity (i.e., rarity) of extreme events. The presented methodology and results could have wide‐ranging applications including training of machine learning methods, Lagrangian‐based evaluation of climate models, and process‐based understanding of extreme precipitation in a changing climate.

Key Clinical Message Reconceptualising acute Musculoskeletal (MSK) injuries with both stress‐ and tissue‐ based factors is required to consider prior influences of mental health disorders on acute persistent MSK pain presentations. This report describes repeated emergency presentations of an individual with acute persistent MSK pain in their twenties living with mental health. Their mental health diagnoses included depression, mood disorders, and anorexia nervosa. This person also had mental health related inpatient admissions that were not captured under the retrospective record review for a large district hospital emergency department using the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT) classification system. This case report attempts to demonstrate that improving the understanding of preexisting vulnerabilities and mental health diagnoses may assist with informing healthcare design to develop specialised care pathways for acute injury presentations within triage settings.

Abstract Introduction People with a low or high haemoglobin glycation index (HGI) have lower or higher HbA1c than other people with the same FPG. This study compared the prevalence of prediabetes based on FPG, 2hOGTT and HbA1c in people with low, moderate or high HGI. Methods Prediabetes was diagnosed based on ADA cutpoints in 10,488 NHANES participants without self‐reported diabetes. HGI was calculated as the difference between a participant's observed HbA1c and a predicted HbA1c where predicted HbA1c = 0.024 FPG + 3.1. Participants were divided into low (HGI +0.15%) HGI subgroups. Results The prevalence of prediabetes was 42.4% based on FPG, 27.2% based on HbA1c and 17.2% based on 2hOGTT. FPG and HbA1c thus overdiagnosed prediabetes by 25.2% and 10.0%, respectively, compared to the OGTT gold standard. Prevalence was (1) similar in low, moderate and high HGI participants based on 2hOGTT, (2) highest in low HGI participants based on FPG, and (3) highest in high HGI participants based on HbA1c. Among participants with mismatched FPG and HbA1c, OGTT was normal in (1) 79.5% of participants with normal FPG but prediabetic HbA1c (mean HGI = +0.53%), and (2) 75.2% of participants with normal HbA1c but prediabetic FPG (mean HGI = −0.30%). Conclusions FPG overdiagnosed prediabetes in people with low HGI. HbA1c overdiagnosed prediabetes in people with high HGI. Clinical use of HGI could improve prediabetes diagnosis and help health care providers avoid inappropriate or delayed treatment of people with extremes of HGI.

Abstract Thousands of colonoscopies were canceled during the initial surge of the COVID‐19 pandemic. As facilities resumed services, some patients were hesitant to reschedule. The purpose of this study was to determine whether a decision aid plus telephone coaching would increase colorectal cancer (CRC) screening and improve patient reports of shared decision making (SDM). A randomized controlled trial assigned adults aged 45–75 without prior history of CRC who had a colonoscopy canceled from March to May 2020 to intervention (n = 400) or usual care control (n = 400) arms. The intervention arm received three‐page decision aid and call from decision coach from September 2020 through November 2020. Screening rates were collected at 6 months. A subset (n = 250) in each arm was surveyed 8 weeks after randomization to assess SDM (scores range 0–4, higher scores indicating more SDM), decisional conflict, and screening preference. The sample was on average, 60 years old, 53% female, 74% White, non‐Hispanic, and 11% Spanish speaking. More intervention arm patients were screened within 6 months (35% intervention vs 23% control, p

Abstract Background Prevention and early intervention can improve survival and quality of life across all cancers. Patient understanding of risk factors and associated actionable lifestyle changes and screening programs is not well understood by clinicians Methods An Internet‐based tool, Reduce My Risk, was created in 2009 and made available on oncolink.org. Users voluntarily completed a survey regarding demographics and cancer risk factors, and received information about their cancer risk Results Twenty eight thousand and one surveys were completed from 2009 to 2019. Median age was 26 years (18–101); 60% were females, 87% lived in North America, and 37% had at least a bachelor's degree. Users reported on behavioral/ modifiable risk factors: 13% were current smokers, 52% were current consumers of alcohol, and 8% of those had ≥14 drinks/week. Body mass index (BMI) was ≥30 in 19%; 74% of all surveys reported dietary risks and 36% reported infrequent exercise. Excess UV exposure was reported by 19%. Among women, 36% reported performing breast self‐examinations monthly, and 50% reported receiving clinician breast examinations at least once every 3 years. Sixty seven percent of men 55–75 years reported screening prostate specific antigen testing, with 50% receiving annual digital rectal examinations. Nonmodifiable risk factors included family cancer history (64%), genetic syndrome (3%), and cancer‐predisposing health conditions (26%) Conclusions Ninety‐seven percent of users reported modifiable risk factors, and 60% reported ≥4 of these risk factors. Understanding detailed characteristics of a large number of respondents has the potential to improve educational interventions to reduce cancer risk through behavioral modification and cancer screening across the general public.

Abstract Soil microbial community's responses to climate warming alter the global carbon cycle. In temperate ecosystems, soil microbial communities function along seasonal cycles. However, little is known about how the responses of soil microbial communities to warming vary when the season changes. In this study, we investigated the seasonal dynamics of soil bacterial community under experimental warming in a temperate tall‐grass prairie ecosystem. Our results showed that warming significantly (p = 0.001) shifted community structure, such that the differences of microbial communities between warming and control plots increased nonlinearly (R2 = 0.578, p = 0.021) from spring to winter. Also, warming significantly (p

Abstract Background Serum symmetric dimethylarginine (SDMA) concentrations are considered a biomarker for renal dysfunction in dogs and humans with acute kidney injury (AKI). No studies have assessed SDMA in cats with AKI. Hypothesis/Objectives SDMA correctly identifies cats with azotemic AKI. Animals Fifteen control cats, 22 with novel AKI, 13 with acute on chronic‐AKI (AoC) and 19 with chronic kidney disease (CKD). Methods Retrospective study. Cats with azotemia (serum creatinine concentrations >1.7 mg/dL) were defined as having AKI or CKD based on history, clinical signs, clinicopathological findings and diagnostic imaging, and classified using the International Renal Interest Society (IRIS) grading/staging systems. Serum SDMA concentrations were compared between groups with nonparametric methods, and correlations assessed using Spearman's correlation coefficient. Data are presented as median [range]. Results SDMA concentrations were 11 (8‐21) μg/dL, 36 (9‐170)μg/dL, 33 (22‐75) μg/dL and 25 (12‐69) μg/dL in control, novel AKI, AoC and CKD cats. SDMA concentrations were significantly higher in cats with novel AKI (P

Abstract Introduction We aimed to streamline the NIDA Phenotyping Assessment Battery (PhAB), a package of self‐report scales and neurobehavioral tasks used in substance use disorder (SUD) clinical trials, for clinical administration ease. Tailoring the PhAB to shorten administration time for a treatment setting is critical to expanding its acceptability in SUD clinical trials. This study's primary objectives were to develop a brief version of PhAB (PhAB‐B) and assess its operational feasibility and acceptability in a female clinical treatment sample. Methods Assessments of the original PhAB were evaluated along several criteria to identify a subset for the PhAB‐B. Non‐pregnant females (N=55) between ages 18–65, stabilized on buprenorphine for opioid use disorder (OUD) at an outpatient addiction clinic, completed this abbreviated battery remotely or after a provider visit in clinic. Participant satisfaction questions were administered. REDCap recorded the time to complete PhAB‐B measures. Results The PhAB‐B included 11 measures that probed reward, cognition, negative emotionality, interoception, metacognition, and sleep. Participants who completed the PhAB‐B (N =55) were 36.1 ± 8.9 years of age, White (54.5%), Black (34.5%), and non‐Latinx (96.0%). Most participants completed the PhAB‐B remotely (n = 42, 76.4%). Some participants completed it in‐person (n = 13, 23.6%). PhAB‐B mean completion time was 23.0 ± 12.0 min. Participant experiences were positive, and 96% of whom reported that they would participate in the study again. Conclusion Our findings support the clinical feasibility and acceptability of the PhAB‐B among a female opioid use disorder outpatient addiction treatment sample. Future studies should assess the PhAB‐B psychometric properties among broader treatment samples.

Background Clinical risk factors, a single blood pressure (BP) measurement, current biomarkers, and biophysical parameters can effectively identify risk of early‐onset preeclampsia but have limited ability to predict later‐onset preeclampsia and gestational hypertension. Clinical BP patterns hold promise to improve early risk stratification for hypertensive disorders of pregnancy. Methods and Results After excluding preexisting hypertension, heart, kidney, or liver disease, or prior preeclampsia, the retrospective cohort (n=249 892) all had systolic BP

Abstract Despite its increasing application to estimate magma decompression rates for explosive eruptions, the embayment speedometer has long awaited critical experimental evaluation. We present the first experimental results on the fidelity of natural quartz‐hosted embayments in rhyolitic systems as recorders of magma decompression. We conducted two high pressure‐temperature isobaric equilibrium experiments and 13 constant‐rate, continuous isothermal decompression experiments in a cold‐seal pressure vessel where we imposed rates from 0.005 to 0.05 MPa s−1 in both H2O‐saturated and mixed‐volatile (H2O + CO2)‐saturated systems. In both equilibrium experiments, we successfully re‐equilibrated embayment melt to new fluid compositions at 780°C and 150 MPa, confirming the ability of embayments to respond to and record changing environmental conditions. Of the 32 glassy embayments recovered, seven met the criteria previously established for successful geospeedometry and were thus analyzed for their volatile (H2O ± CO2) concentrations, with each producing a good model fit and recovering close to the imposed decompression rate. In one H2O‐saturated experiment, modeling H2O concentration gradients in embayments from three separate crystals resulted in best‐fit decompression rates ranging from 0.012 to 0.021 MPa s−1, in close agreement with the imposed rate (0.015 MPa s−1) and attesting to the reproducibility of the technique. For mixed‐volatile experiments, we found that a slightly variable starting fluid composition (2.4–3.5 wt.% H2O at 150 MPa) resulted in good fits to both H2O + CO2 profiles. Overall our experiments provide confidence that the embayment is a robust recorder of constant‐rate, continuous decompression, with the model successfully extracting experimental conditions from profiles representing nearly an order of magnitude variation (0.008–0.05 MPa s−1) in decompression rate.

Abstract Objective To characterize the burden of illness associated with oral factor Xa (FXa) inhibitor‐related bleeding in the US Medicare population. Methods This retrospective cohort study used the full 20% Medicare random sample claims database to identify patients who experienced their first hospitalization for an FXa inhibitor‐related major bleed between October 2013 and September 2017. Bleeding types were classified as intracranial hemorrhage (ICH), gastrointestinal (GI), and other. Associations between risk factors and outcomes (in‐hospital and 30‐day mortality, 30‐day readmission, and discharge to a location other than home) adjusted for patient demographic characteristics, baseline clinical conditions, index event characteristics, treatment with hemostatic/factor replacement agents or transfusion (ie, usual care prereversal agent availability), multicompartment ICH and neurosurgical procedures (ICH cohort), and endoscopy (GI cohort) were assessed using multivariable regression and reported as crude incidences and adjusted odds ratios (ORs) stratified by bleed type. Results Of the 11,593 patients identified, 2737 (23.6%) had ICH, 8169 (70.5%) had GI bleeds, and 687 (5.9%) had other bleeds. The incidences of in‐hospital mortality, 30‐day mortality, need for postdischarge out‐of‐home care, and 30‐day readmission were 15.7%, 29.1%, 78.3%, and 20.3% in the single‐compartment ICH cohort, respectively; and 1.7%, 6.8%, 41.3%, and 18.8% in the GI bleeds cohort, respectively. Increased odds of both in‐hospital mortality and 30‐day mortality were significantly associated with: multicompartment ICH (reference, single compartment ICH; OR = 3.35 [95% confidence interval (CI): 2.41–4.66]; 2.18 [95% CI: 1.63–2.91]), loss of consciousness during index hospitalization (yes vs no; OR = 2.03 [95% CI: 1.38–2.97]; 1.49 [95% CI: 1.11–2.02]), receiving usual care (yes vs no; OR = 1.55 [95% CI: 1.22–1.98]; 1.33 [95% CI: 1.09–1.63]) during index hospitalization, and increasing number of Elixhauser comorbidities at baseline (OR = 1.07 [95% CI: 1.03–1.10]; 1.09 [95% CI: 1.06–1.12]) in the ICH cohort; intensive care unit admission (yes vs no; OR = 1.88 [95% CI: 1.32–2.67]; 1.51 [95% CI: 1.26–1.81]), increasing number of Elixhauser comorbidities at baseline (OR = 1.12 [95% CI: 1.07–1.18]; 1.15 [1.12–1.18]), and increasing age on index date (OR = 1.04 [95% CI: 1.02–1.07]; 1.05 [95% CI: 1.04–1.07]) in the GI bleeds cohort. Conclusions In this large sample of Medicare patients, FXa inhibitor‐related major bleeding was associated with substantial burden in terms of adverse clinical outcomes and health care resource use. Incidence of ICH was lower than GI bleeds; however, burden of illness was notably higher with ICH.

Abstract Climate warming and eutrophication are leading drivers of environmental change, and both are likely to alter the role of freshwaters in the global carbon cycle. Recent studies demonstrate that warming of streams can increase freshwater contributions of CO2 to the atmosphere, yet little is known about how such contributions are modulated by the identity or supply of limiting nutrients. We quantified responses of ecosystem metabolism and metabolic balance to whole‐stream enrichments of either nitrogen or phosphorus across a 5°C range of ambient temperature. We show that nutrient enrichment drove large reductions in net ecosystem production, and interactions with temperature amplified these effects in warm N‐enriched streams. Partitioning of autotrophic and heterotrophic respiration revealed that these responses were driven by increased respiration of microbial heterotrophs. Our study provides direct experimental evidence that warming‐induced increases in CO2 emissions to the atmosphere are likely intensified in stream ecosystems subject to eutrophication.

Abstract A greater understanding of eDNA behavior in the environment is needed before it can be employed for ecosystem monitoring applications. The objectives of this study were to use autonomous sampling to conduct long‐term, high‐frequency monitoring of the eDNA of native salmonid species in a Californian coastal stream, describe temporal variation of eDNA on multiple scales and identify environmental factors that drive this variation, and evaluate the ability of the eDNA datasets to detect rare species and represent organismal abundance. Using high‐throughput autonomous environmental sample processors (ESPs) and qPCR, we enumerated eDNA concentrations from 674 water samples collected at subdaily intervals over 360 days at a single site. We detected eDNA from two imperiled salmonids (coho salmon Oncorhynchus kisutch and steelhead/rainbow trout O. mykiss) in most samples; O. kisutch eDNA was generally in lower concentration and more variable than O. mykiss eDNA. High‐frequency (i.e., subdaily and daily) variability in salmonid eDNA concentrations showed occasional patchiness (i.e., large differences between consecutive samples), while seasonal differences were observed consistent with the ecology of the species at this site. Salmonid eDNA concentrations were significantly associated with creek discharge, photoperiod, and whether the creek mouth was open or closed by a seasonal sandbar. The release of hatchery‐origin O. kisutch parr into the stream was associated with a significant increase in eDNA concentration for the remainder of the study. We compared eDNA signals with fish abundance data collected from traps located at the site. Fish were detected more often by eDNA than from trapping. Significant positive associations between fish abundance and eDNA concentrations were observed for O. mykiss; however, no such associations were observed for O. kisutch. This study adds to our knowledge on the occurrence and behavior of fish eDNA in lotic systems and informs future biomonitoring efforts using automated sampling technology.