Search

Abstract Aims Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD‐code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. Methods and results The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP‐HF) and non‐HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF‐related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP‐HF as cases (PPV, 0.86; sensitivity, 0.86). From the ‘HF ICD‐code universe’, we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). Conclusions These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.

Abstract Foraging behaviors often involve trade‐offs between predation risk and access to forage. Risk‐forage trade‐offs may be particularly acute for maternal female ungulates, whose nutritional needs are high and whose calves are highly vulnerable to predation. In moose, the selection of calving habitat is one way in which females can respond to these trade‐offs. Our objective was to compare among‐individual variation in selected habitat for maternal and nonmaternal female moose during the calving season. We hypothesized that, compared to nonmaternal females, maternal females would exhibit a greater range of variation among individuals, which may signal differential responses to risk‐forage trade‐offs. Meanwhile, we expected nonmaternal females to show comparatively less variation among individuals, consistent with a group primarily maximizing forage intake. To test our hypotheses, we used a path selection framework and a set of continuous remotely sensed map covariates to build predictive models and corresponding spatial predictions for maternal and nonmaternal groups. We then calculated the range of variation among individuals within each group along a relative unitless axis, which we call the “maternal difference index” and define as the divergence of predicted maternal habitat selection from nonmaternal habitat selection. We included 10,080 GPS collar locations for 24 female moose over three consecutive years. Our predictive models had high levels of accuracy (>75%) based both on independent test partitions of a nested cross‐validation and on independent very high frequency (VHF) location data, each including spatial and temporal replication. Both groups of females preferred areas where primary forage species were abundant, diverse, and within foraging height. Habitat selected by the maternal group both overlapped and was broader than habitat selected by the nonmaternal group. Based on the maternal difference index, maternal individuals were less consistent in their habitat selection than nonmaternal individuals. Given that habitat selection behaviors are one way in which animals respond to potential risk‐forage trade‐offs and that maternal individuals in our study differed along a continuum in their selection for primary forage species, we suggest that the concept of maternal trade‐offs, as it relates to habitat selection, is most useful when seen as individually determined and variable, rather than group‐determined and discrete.

Background Early detection of left and right ventricular systolic dysfunction (LVSD and RVSD respectively) in children can lead to intervention to reduce morbidity and death. Existing artificial intelligence algorithms can identify LVSD and RVSD in adults using a 12‐lead ECG; however, its efficacy in children is uncertain. We aimed to develop novel artificial intelligence–enabled ECG algorithms for LVSD and RVSD detection in pediatric patients. Methods and Results We identified 10 142 unique pediatric patients (age≤18) with a 10‐second, 12‐lead surface ECG within 14 days of a transthoracic echocardiogram, performed between 2002 and 2022. LVSD was defined quantitatively by left ventricular ejection fraction (LVEF). RVSD was defined semiquantitatively. Novel pediatric models for LVEF ≤35% and LVEF

Abstract Although bold and shy behavioral phenotypes in zebrafish (Danio rerio) have been selectively bred and maintained over multiple generations, it is unclear if they are underscored by different gut microbiota. Using the microbiota–gut–brain concept, we examined the relationship between gut microbiota and the behavioral phenotypes within this model animal system to assess possible gut microbe‐mediated effects on host behavior. To this end, we amplified and sequenced 16S rRNA gene amplicons from the guts of bold and shy zebrafish individuals using the Illumina Miseq platform. We did not record any significant differences in within‐group microbial diversity nor between‐group community composition of the two behavioral phenotypes. Interestingly, though not statistically different, we determined that the gut microbial community of the bold phenotype was dominated by Burkholderiaceae, Micropepsaceae, and Propionibacteriaceae. In contrast, the shy phenotype was dominated by Beijerinckaceae, Pirelullacaeae, Rhizobiales_Incertis_Sedis, and Rubinishaeraceae. The absence of any significant difference in gut microbiome profiles between the two phenotypes would suggest that in this species, there might exist a stable core gut microbiome, regardless of behavioral phenotypes, and possibly, a limited role for the gut microbiota in modulating this selected‐for host behavior. This study characterized the gut microbiomes of distinct innate behavioral phenotypes of the zebrafish (that are not considered dysbiotic states) and did not rely on antibiotic or probiotic treatments to induce changes in behavior. Such studies are crucial to our understanding of the modulating impacts of the gut microbiome on normative animal behavior.

ABSTRACT Objectives In ovarian and other cancers, low muscle mass and density are associated with poorer clinical outcomes. However, screening for cancer‐related sarcopenia (typically defined as low muscle mass) is not routinely conducted. The European Working Group on Sarcopenia in Older People (EWGSOP) recommends an algorithm for sarcopenia screening and diagnosis in clinical settings, with sarcopenia based on muscle strength and mass, and severity on physical performance. We explored the application of the EWGSOP2 algorithm to assess sarcopenia in six ovarian cancer patients receiving neoadjuvant chemotherapy. Methods We assessed sarcopenia risk with the SARC‐F screening questionnaire (at risk ≥4 points), muscle strength with a handgrip strength test (cut point 15 s), muscle mass by skeletal muscle index (SMI in cm2/m2 from a single computed tomography [CT] image; cut point

Background The study aimed to describe the patterns and trends of initiation, discontinuation, and adherence of oral anticoagulation (OAC) in patients with new‐onset postoperative atrial fibrillation (POAF), and compare with patients newly diagnosed with non‐POAF. Methods and Results This retrospective cohort study identified patients newly diagnosed with atrial fibrillation or flutter between 2012 and 2021 using administrative claims data from OptumLabs Data Warehouse. The POAF cohort included 118 366 patients newly diagnosed with atrial fibrillation or flutter within 30 days after surgery. The non‐POAF cohort included the remaining 315 832 patients who were newly diagnosed with atrial fibrillation or flutter but not within 30 days after a surgery. OAC initiation increased from 28.9% to 44.0% from 2012 to 2021 in POAF, and 37.8% to 59.9% in non‐POAF; 12‐month medication adherence increased from 47.0% to 61.8% in POAF, and 59.7% to 70.4% in non‐POAF. The median time to OAC discontinuation was 177 days for POAF, and 242 days for non‐POAF. Patients who saw a cardiologist within 90 days of the first atrial fibrillation or flutter diagnosis, regardless of POAF or non‐POAF, were more likely to initiate OAC (odds ratio, 2.92 [95% CI, 2.87–2.98]; P

Abstract Applying machine learning to continuous acoustic emissions, signals previously deemed noise, from laboratory faults and slowly slipping subduction‐zone faults, demonstrates hidden signatures are emitted that describe physical details, including fault displacement and friction. However, no evidence currently exists to demonstrate that similar hidden signals occur during seismogenic stick‐slip on earthquake faults—the damaging earthquakes of most societal interest. We show that continuous seismic emissions emitted during the 2018 multi‐month caldera collapse sequence at the Kı̄lauea volcano in Hawai'i contain hidden signatures characterizing the earthquake cycle. Multi‐spectral data features extracted from 30 s intervals of the continuous seismic emission are used to train a gradient boosted tree regression model to predict the GNSS‐derived contemporaneous surface displacement and time‐to‐failure of the upcoming collapse event. This striking result suggests that at least some faults emit such signals and provide a potential path to characterizing the instantaneous and future behavior of earthquake faults.

Abstract Minimally invasive samples are often the best option for collecting genetic material from species of conservation concern, but they perform poorly in many genomic sequencing methods due to their tendency to yield low DNA quality and quantity. Genotyping‐in‐thousands by sequencing (GT‐seq) is a powerful amplicon sequencing method that can genotype large numbers of variable‐quality samples at a standardized set of single nucleotide polymorphism (SNP) loci. Here, we develop, optimize, and validate a GT‐seq panel for the federally threatened northern Idaho ground squirrel (Urocitellus brunneus) to provide a standardized approach for future genetic monitoring and assessment of recovery goals using minimally invasive samples. The optimized panel consists of 224 neutral and 81 putatively adaptive SNPs. DNA collected from buccal swabs from 2016 to 2020 had 73% genotyping success, while samples collected from hair from 2002 to 2006 had little to no DNA remaining and did not genotype successfully. We evaluated our GT‐seq panel by measuring genotype discordance rates compared to RADseq and whole‐genome sequencing. GT‐seq and other sequencing methods had similar population diversity and FST estimates, but GT‐seq consistently called more heterozygotes than expected, resulting in negative FIS values at the population level. Genetic ancestry assignment was consistent when estimated with different sequencing methods and numbers of loci. Our GT‐seq panel is an effective and efficient genotyping tool that will aid in the monitoring and recovery of this threatened species, and our results provide insights for applying GT‐seq for minimally invasive DNA sampling techniques in other rare animals.

Abstract Flatback turtles (Natator depressus) are endemic to northern Australia, but their movements at sea have remained understudied. Here, we compiled one of the world's largest single‐species satellite tracking datasets (n = 280 transmitters, deployed between 2005 and 2020) to investigate the movements and level of spatial protection afforded to five flatback genetic stocks across Western Australia during different behavioral phases (i.e., inter‐nesting, migration, and foraging). Flatbacks spent 99.5% of their time in Australian waters and are provided with a very high level of spatial protection (>98% overlap with Biologically Important Areas) during the inter‐nesting phase of their life cycle. Up to 85.6% and 59.1% overlap between marine reserves and the foraging and migratory ranges for flatback stocks, respectively, was found. However, our results identified additional foraging and migratory areas where protective measures would benefit multiple stocks at once. The detailed flatback distribution maps produced here will be key resources for managers and researchers and highlight the benefits of collaborative multi‐agency studies. Additionally, this work provides a useful analytical framework for future studies endeavoring to complete large‐scale, multi‐stock spatial distributions and overlap assessments for populations of conservation concern.

Background Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low‐density lipoprotein cholesterol (VLDL‐C) and lipid discordance could be contributors to the residual risk of ASCVD. Methods and Results Cardiovascular disease–free residents, aged ≥40 years, living in Olmsted County, Minnesota, were identified through the Rochester Epidemiology Project. Low‐density lipoprotein cholesterol (LDL‐C) and VLDL‐C were estimated from clinically ordered lipid panels using the Sampson equation. Participants were categorized into concordant and discordant lipid pairings based on clinical cut points. Rates of incident ASCVD, including percutaneous coronary intervention, coronary artery bypass grafting, stroke, or myocardial infarction, were calculated during follow‐up. The association of LDL‐C and VLDL‐C with ASCVD was assessed using Cox proportional hazards regression. Interaction between LDL‐C and VLDL‐C was assessed. The study population (n=39 098) was primarily White race (94%) and female sex (57%), with a mean age of 54 years. VLDL‐C (per 10‐mg/dL increase) was significantly associated with an increased risk of incident ASCVD (hazard ratio, 1.07 [95% CI, 1.05–1.09]; P

Abstract Introduction Invasive neuromodulation interventions such as deep brain stimulation (DBS) and vagal nerve stimulation (VNS) are important treatments for movement disorders and epilepsy, but literature focused on young patients treated with DBS and VNS is limited. This retrospective study aimed to examine naturalistic outcomes of VNS and DBS treatment of epilepsy and dystonia in children, adolescents, and young adults. Methods We retrospectively assessed patient demographic and outcome data that were obtained from electronic health records. Two researchers used the Clinical Global Impression scale to retrospectively rate the severity of neurologic and psychiatric symptoms before and after patients underwent surgery to implant DBS electrodes or a VNS device. Descriptive and inferential statistics were used to examine clinical effects. Results Data from 73 patients were evaluated. Neurologic symptoms improved for patients treated with DBS and VNS (p

Abstract Background Aspirin use has been associated with reduced ovarian cancer risk, yet the underlying biological mechanisms are not fully understood. To gain mechanistic insights, we assessed the association between prediagnosis low and regular‐dose aspirin use and gene expression profiles in ovarian tumors. Methods RNA sequencing was performed on high‐grade serous, poorly differentiated, and high‐grade endometrioid ovarian cancer tumors from the Nurses' Health Study (NHS), NHSII, and New England Case–Control Study (n = 92 cases for low, 153 cases for regular‐dose aspirin). Linear regression identified differentially expressed genes associated with aspirin use, adjusted for birth decade and cohort. False discovery rates (FDR) were used to account for multiple testing and gene set enrichment analysis was used to identify biological pathways. Results No individual genes were significantly differentially expressed in ovarian tumors in low or regular‐dose aspirin users accounting for multiple comparisons. However, current versus never use of low‐dose aspirin was associated with upregulation of immune pathways (e.g., allograft rejection, FDR = 5.8 × 10−10; interferon‐gamma response, FDR = 2.0 × 10−4) and downregulation of estrogen response pathways (e.g., estrogen response late, FDR = 4.9 × 10−8). Ovarian tumors from current regular aspirin users versus never users were also associated with upregulation in interferon pathways (FDR

Abstract Aims Specialist cardiology care is associated with a prognostic benefit in patients with heart failure (HF) with reduced ejection fraction (HFrEF) admitted with decompensated HF. However, up to one third of patients admitted with HF and normal ejection fraction (HFnEF) do not receive specialist cardiology input. Whether this has prognostic implications is unknown. Methods and results Data on patients hospitalized with HFnEF from two tertiary centres were analysed. The primary outcome measure was all‐cause mortality during follow‐up. The secondary outcome was in‐hospital mortality. A total of 1413 patients were included in the study. Of these, 23% (n = 322) did not receive in‐hospital specialist cardiology input. Patients seen by a cardiologist were less likely to have hypertension (73% vs. 79%, P = 0.03) and respiratory co‐morbidities (25% vs. 31%, P = 0.02) compared with those who did not receive specialist input. Similarly, clinical presentation was more severe for those who received specialist input (New York Heart Association III/IV 83% vs. 75% respectively, P = 0.003; moderate‐to‐severe peripheral oedema 65% vs. 54%, P

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 Pulmonary hypertension (PH) is a severe medical condition with a number of treatment options, the majority of which are introduced without consideration of the underlying mechanisms driving it within an individual and thus a lack of tailored approach to treatment. The one exception is a patient presenting with apparent pulmonary arterial hypertension and shown to have vaso‐responsive disease, whose clinical course and prognosis is significantly improved by high dose calcium channel blockers. PH is however characterized by a relative abundance of available data from patient cohorts, ranging from molecular data characterizing gene and protein expression in different tissues to physiological data at the organ level and clinical information. Integrating available data with mechanistic information at the different scales into computational models suggests an approach to a more personalized treatment of the disease using model‐based optimization of interventions for individual patients. That is, constructing digital twins of the disease, customized to a patient, promises to be a key technology for personalized medicine, with the aim of optimizing use of existing treatments and developing novel interventions, such as new drugs. This article presents a perspective on this approach in the context of a review of existing computational models for different aspects of the disease, and it lays out a roadmap for a path to realizing it.

Background Posttraumatic stress disorder (PTSD) has been associated with ischemic heart disease in women veterans, but evidence for associations with other cardiovascular disorders remains limited in this population. This retrospective longitudinal cohort study evaluated the association of PTSD with incident stroke/transient ischemic attack (TIA) in women veterans. Methods and Results Veterans Health Administration electronic health records were used to identify women veterans aged ≥18 years engaged with Veterans Health Administration health care from January 1, 2000 to December 31, 2019. We identified women veterans with and without PTSD without a history of stroke or TIA at start of follow‐up. Propensity score matching was used to match groups on age, race or ethnicity, traditional cardiovascular risk factors, female‐specific risk factors, a range of mental and physical health conditions, and number of prior health care visits. PTSD, stroke, TIA, and risk factors used in propensity score matching were based on diagnostic codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs for associations of PTSD with an incident stroke/TIA composite. Subanalyses considered stroke and TIA separately, plus age‐ and race‐ or ethnicity‐stratified analyses were carried out. The analytic sample included 208 092 women veterans (104 046 with and 104 046 without PTSD). PTSD was associated with a greater rate of developing stroke/TIA (HR, 1.33 [95% CI, 1.25–1.42], P

Abstract Conservation funding is currently limited; cost‐effective conservation solutions are essential. We suggest that the thousands of field stations worldwide can play key roles at the frontline of biodiversity conservation and have high intrinsic value. We assessed field stations’ conservation return on investment and explored the impact of COVID‐19. We surveyed leaders of field stations across tropical regions that host primate research; 157 field stations in 56 countries responded. Respondents reported improved habitat quality and reduced hunting rates at over 80% of field stations and lower operational costs per km2 than protected areas, yet half of those surveyed have less funding now than in 2019. Spatial analyses support field station presence as reducing deforestation. These “earth observatories” provide a high return on investment; we advocate for increased support of field station programs and for governments to support their vital conservation efforts by investing accordingly.

Abstract The Chilean volcano Cerro Hudson erupted between August 8th and 15th, 1991, injecting between 1.7 and 2.9 Tg of SO2 into the upper troposphere and lower stratosphere. We simulate this injection using the Goddard Earth Observing System Earth system model with detailed sulfur chemistry and sectional aerosol microphysics, focusing on the resulting aerosols and their contribution to the 1991 Antarctic Austral Springtime ozone hole. The simulations show a column ozone deficit (12 DU) in the Southern Hemisphere vortex collar region. The majority of this effect is between 10 and 20 km and due to heterogeneous chemistry. The model shows a 26% decrease in ozone from background levels at these altitudes, compared with in‐situ observations of a 50% decrease. Above 20 km, the dynamical response to the eruption also causes lower ozone values, a novel modeling result. This experiment highlights potential interactions between proposed solar radiation management geoengineering aerosols and volcanic eruptions.

Abstract The protein kinase Mechanistic Target of Rapamycin (mTOR) in Complex 1 (mTORC1) is regulated in part by the Ras‐related GTP‐binding proteins (Rag GTPases). Rag GTPases form a heterodimeric complex consisting of either RagA or RagB associated with either RagC or RagD and act to localize mTORC1 to the lysosomal membrane. Until recently, RagA and RagB were thought to be functionally redundant, as were RagC and RagD. However, recent research suggests that the various isoforms differentially activate mTORC1. Here, the mRNA expression and protein abundance of the Rag GTPases was compared across male rat skeletal muscle, heart, liver, kidney, and brain. Whereas mRNA expression of RagA was higher than RagB in nearly all tissues studied, RagB protein abundance was higher than RagA in all tissues besides skeletal muscle. RagC mRNA expression was more abundant or equal to RagD mRNA, and RagD protein was more abundant than RagC protein in all tissues. Moreover, the proportion of RagB in the short isoform was greater than the long in liver, whereas the opposite was true in brain. These results serve to further elucidate Rag GTPase expression and offer potential explanations for the differential responses to amino acids that are observed in different tissues.

Abstract Semi‐enclosed seas are often associated with elevated local threats and distinct biogeographic patterns among marine fishes, but our understanding of how fish assemblage dynamics vary in relation to relatively small semi‐enclosed seas (e.g., the Gulf of Aqaba) remains limited. Baited remote underwater video surveys (n = 111) were conducted across ~300 km of coral reef habitats in the Gulf of Aqaba and the northern Red Sea. A total of 55 predatory fish species were detected, with less than half of all species (n = 23) observed in both basins. Relative abundance patterns between the Gulf of Aqaba and the northern Red Sea were variable among taxa, but nearly twice as many predatory fish were observed per unit of effort in the northern Red Sea. In general, assemblages in both basins were dominated by three taxa (Epinephelinae, Carangidae, and Lethrinidae). Large‐bodied and threatened species were recorded at very low abundances. Multivariate analysis revealed distinct assemblage structuring of coral reef predators between the Gulf of Aqaba and the northern Red Sea. Most of the species driving these differences were recorded in both basins, but occurred at varying levels of abundance. Environmental factors were largely unsuccessful in explaining variation in assemblage structuring. These findings indicate that biological assemblages in the Gulf of Aqaba are more distinct than previously reported and that reef fish assemblage structuring can occur even within a relatively small semi‐enclosed sea. Despite inter‐basin assemblage structuring, the overall low abundance of vulnerable fish species is suggestive of overexploitation in both the Gulf of Aqaba and the northern Red Sea of Saudi Arabia. As the region surveyed is currently undergoing large‐scale coastal development, the results presented herein aim to guide spatial management and recovery plans for these coral reef systems in relation to this development.

Background Little is known about hospital pricing for coronary artery bypass grafting (CABG). Using new price transparency data, we assessed variation in CABG prices across US hospitals and the association between higher prices and hospital characteristics, including quality of care. Methods and Results Prices for diagnosis related group code 236 were obtained from the Turquoise database and linked by Medicare Facility ID to publicly available hospital characteristics. Univariate and multivariable analyses were performed to assess factors predictive of higher prices. Across 544 hospitals, median commercial and self‐pay rates were 2.01 and 2.64 times the Medicare rate ($57 240 and $75 047, respectively, versus $28 398). Within hospitals, the 90th percentile insurer‐negotiated price was 1.83 times the 10th percentile price. Across hospitals, the 90th percentile commercial rate was 2.91 times the 10th percentile hospital rate. Regional median hospital prices ranged from $35 624 in the East South Central to $84 080 in the Pacific. In univariate analysis, higher inpatient revenue, greater annual discharges, and major teaching status were significantly associated with higher prices. In multivariable analysis, major teaching and investor‐owned status were associated with significantly higher prices (+$8653 and +$12 200, respectively). CABG prices were not related to death, readmissions, patient ratings, or overall Centers for Medicare and Medicaid Services hospital rating. Conclusions There is significant variation in CABG pricing, with certain characteristics associated with higher rates, including major teaching status and investor ownership. Notably, higher CABG prices were not associated with better‐quality care, suggesting a need for further investigation into drivers of pricing variation and the implications for health care spending and access.

Abstract Molecular tools are increasingly applied for assessing and monitoring biodiversity and informing conservation action. While recent developments in genetic and genomic methods provide greater sensitivity in analysis and the capacity to address new questions, they are not equally available to all practitioners: There is considerable bias across institutions and countries in access to technologies, funding, and training. Consequently, in many cases, more accessible traditional genetic data (e.g., microsatellites) are still utilized for making conservation decisions. Conservation approaches need to be pragmatic by tackling clearly defined management questions and using the most appropriate methods available, while maximizing the use of limited resources. Here we present some key questions to consider when applying the molecular toolbox for accessible and actionable conservation management. Finally, we highlight a number of important steps to be addressed in a collaborative way, which can facilitate the broad integration of molecular data into conservation.

Abstract Infectious diseases are a major threat for biodiversity conservation and can exert strong influence on wildlife population dynamics. Understanding the mechanisms driving infection rates and epidemic outcomes requires empirical data on the evolutionary trajectory of pathogens and host selective processes. Phylodynamics is a robust framework to understand the interaction of pathogen evolutionary processes with epidemiological dynamics, providing a powerful tool to evaluate disease control strategies. Tasmanian devils have been threatened by a fatal transmissible cancer, devil facial tumour disease (DFTD), for more than two decades. Here we employ a phylodynamic approach using tumour mitochondrial genomes to assess the role of tumour genetic diversity in epidemiological and population dynamics in a devil population subject to 12 years of intensive monitoring, since the beginning of the epidemic outbreak. DFTD molecular clock estimates of disease introduction mirrored observed estimates in the field, and DFTD genetic diversity was positively correlated with estimates of devil population size. However, prevalence and force of infection were the lowest when devil population size and tumour genetic diversity was the highest. This could be due to either differential virulence or transmissibility in tumour lineages or the development of host defence strategies against infection. Our results support the view that evolutionary processes and epidemiological trade‐offs can drive host‐pathogen coexistence, even when disease‐induced mortality is extremely high. We highlight the importance of integrating pathogen and population evolutionary interactions to better understand long‐term epidemic dynamics and evaluating disease control strategies.

Abstract Fat accumulation during liver steatosis precedes inflammation and fibrosis in fatty liver diseases, and is associated with disease progression. Despite a large body of evidence that liver mechanics play a major role in liver disease progression, the effect of fat accumulation by itself on liver mechanics remains unclear. Thus, we conducted ex vivo studies of liver mechanics in rodent models of simple steatosis to isolate and examine the mechanical effects of intrahepatic fat accumulation, and found that fat accumulation softens the liver. Using a novel adaptation of microindentation to permit association of local mechanics with microarchitectural features, we found evidence that the softening of fatty liver results from local softening of fatty regions rather than uniform softening of the liver. These results suggest that fat accumulation itself exerts a softening effect on liver tissue. This, along with the localized heterogeneity of softening within the liver, has implications in what mechanical mechanisms are involved in the progression of liver steatosis to more severe pathologies and disease. Finally, the ability to examine and associate local mechanics with microarchitectural features is potentially applicable to the study of the role of heterogeneous mechanical microenvironments in both other liver pathologies and other organ systems.

Abstract Background Poor comprehenders are traditionally identified as having below‐average reading comprehension, average‐range word reading, and a discrepancy between the two. While oral language tends to be low in poor comprehenders, reading is a complex trait and heterogeneity may go undetected by group‐level comparisons. Methods We took a preregistered data‐driven approach to identify poor comprehenders and examine whether multiple distinct cognitive profiles underlie their difficulties. Latent mixture modelling identified reading profiles in 6846 children from the Avon Longitudinal Study of Parents and Children, based on reading and listening comprehension assessments at 8–9 years. A second mixture model examined variation in the cognitive profiles of weak comprehenders, using measures of reading, language, working memory, nonverbal ability, and inattention. Results A poor comprehender profile was not identified by the preregistered model. However, by additionally controlling for overall ability, a 6‐class model emerged that incorporated a profile with relatively weak comprehension (N = 947, 13.83%). Most of these children had weak reading comprehension in the context of good passage reading, accompanied by weaknesses in vocabulary and nonverbal ability. A small subgroup showed more severe comprehension difficulties in the context of additional cognitive impairments. Conclusions Isolated impairments in specific components of reading are rare, yet a data‐driven approach can be used to identify children with relatively weak comprehension. Vocabulary and nonverbal ability were most consistently weak within this group, with broader cognitive difficulties also apparent for a subset of children. These findings suggest that poor comprehension is best characterised along a continuum, and considered in light of multiple risks that influence severity.

Key Clinical Message Inherited retinal dystrophies typically affect vision in early childhood; however, this case highlights a late onset retinal dystrophy presenting in midlife and the need for extended visual electrophysiology testing to determine the etiology. Abstract A 53‐year‐old female was referred for visual electrophysiology following a routine optometric eye examination in which yellow flecks were noted in both fundi and the patient had reported a recent near accident whilst driving at night. There was no reported family history of eye disease. Retinal examination identified bilateral yellow punctate and irregularly shaped lesions throughout the posterior poles sparing the macula region. Fundus autofluorescence showed coinciding hyperfluorescence with the lesions and bilateral hypofluorescent crescents superior to the macular with corresponding retinal thinning. Visual fields and color vision were normal. ISCEV standard 20 min and extended 60‐min dark adapted electroretinograms were recorded. Recovery to normal b‐wave amplitudes was noted in the DA0.01 flash but reduced a‐wave amplitudes were noted in the DA3 and DA10 flash following both dark adapted periods. Cone function was reduced but within normal limits. Genetic screening revealed a previously unreported variant of unknown significance in the gene PLA2G5:c.40 + 5del (rs1364254561) which is a member of the phospholipase A2 family and is associated with familial benign flecked retina.

Abstract Water infiltration into fractures is ubiquitous in crustal rocks. However, little is known about how such a progressive wetting process affects fracture stiffness and seismic wave propagation, which are highly relevant for characterizing fracture systems in situ. We study the acousto‐mechanical behavior of a free‐standing fractured granite subjected to gradual water infiltration with a downward‐moving wetting front over 12 days. We observe significant differences (i.e., by an order of magnitude) in wave amplitudes across the fractured granite compared to an intact granite, with both cases showing a strong correlation between wave amplitudes and wetting front movement. Effects of water infiltration into the fracture and surrounding matrix on seismic attenuation are captured by a numerical model with parameters constrained by experimental data. Back‐calculated fracture stiffness decreases exponentially with the wetting front migration along the fracture. We propose that moisture‐induced matrix expansion around the fracture increases asperity mismatch, leading to reduced fracture stiffness.

Abstract Background and Aims Modern health care faces a plethora of challenges including the delivery of quality and cost‐efficient care. Physicians are first‐hand observers of clinical problems but may lack the requisite training and education to develop innovations that improve patient care. Few medical education programs address innovation, leadership, and transdisciplinary collaboration despite being highlighted by national medical and education organizations including the American Medical Association. The University of Minnesota has implemented the Augustine program over the last 10‐years to produce physicians that are leaders in medical innovation. Methods As a novel joint engineering‐medical school curriculum to educate medical students, residents, and fellows, the Augustine program incorporates engineering coursework, biomedical research, and a multidisciplinary design and business development experience to produce physicians capable of designing and marketing “disruptive technologies.” The Augustine program takes 1‐year to complete in addition to the 4‐year medical education and provides a Master of Biomedical Engineering upon completion. Results Augustine program graduates (n = 6) have reported significant contributions related to the joint engineering‐medical education including peer‐reviewed publications (Median: 13), deployable assets (Median: 2), and intellectual property (Median: 1). Most surveyed graduates (n = 5, 83%) continue to be active contributors to medical innovation and all (n = 6, 100%) utilize their transdisciplinary education to improve patient care. Conclusion Augustine program graduates impact the entire spectrum of innovation and continue to improve patient care. The program will seek to emphasize the inclusion of physician residents and fellows with position expansion. The addition of a multi‐week medical innovation clerkship will provide a more focused experience for students unable to dedicate an entire year to a transdisciplinary experience.

Abstract Aims Secondary mitral regurgitation (SMR) is frequent in patients with heart failure with reduced ejection fraction (HFrEF) and portends detrimental prognosis. Despite interventions addressing the mitral valve (MV) have been proven effective to improve survival, an important knowledge gap exists regarding the role of medical therapy (MT) in this context. Thus, we aimed at investigating the role of MT optimization in patients with SMR and HFrEF. Methods and results A total of 435 patients with SMR and HFrEF were retrospectively evaluated. Of those, 158 with severe SMR were finally included, with 63 (40%) managed with MT alone and 96 (60%) with MV intervention plus MT. Echocardiography was performed after 30 days of MT optimization or MV intervention. Responders were patients with a final mitral regurgitation (MR) grade of ≤2+. Survival data were gathered through the National Database Index and patient chart review. MR severity improved in 131 patients (100% MV intervention; 57% MT) but stayed the same or worsened in 27 patients. Responders and non‐responders were similar for baseline characteristics. Overall, long‐term survival of responders was significantly higher than non‐responders [hazard ratio (HR) 0.55, 95% confidence interval (CI) (0.32–0.96), P = 0.032]. No difference in survival was observed when evaluated by intervention type in the overall population (MT alone, n = 63; MV intervention plus MT, n = 95) [HR 0.77, 95% CI (0.48–1.26), P = 0.3], nor within responder group (MT alone, n = 36; MV intervention plus MT, n = 95) [HR 1.03, 95% CI (0.56–1.89), P = 0.94]. Conclusions MT reduces SMR severity in 57% of the patients with severe SMR. A final SMR grade of ≤2+ is linked to improved survival, independently of the type of treatment they receive.

Abstract Aims The long‐term outcome in patients with heart failure (HF) after hospitalization may vary substantially depending on their age and left ventricular ejection fraction (LVEF). We aimed to assess the relative rates of cardiovascular death (CVD) and non‐CVD based on the age and how the rates differ under the updated LVEF classification system. Methods and results Consecutively registered hospitalized patients with HF (N = 3558; 39.7% women with a mean age of 73.9 ± 13.3 years) were followed for a median of 2 (interquartile range, 0.8–3.1) years. The CVDs and non‐CVDs were evaluated based on age [young (

Abstract Diffuse large B‐cell lymphoma (DLBCL) arising in the spleen, also known as primary splenic DLBCL (PS‐DLBCL), is a rare form of malignant lymphoma. It is defined as a lymphoma confined to the spleen or involving splenic hilar lymph nodes. Here we report a case of PS‐DLBCL with CD30. The patient was a 62‐year‐old who presented with 2 weeks of left flank pain, chills, and abdominal distension. Computed tomography identified an 8‐cm splenic mass with central necrosis interpreted as an abscess. A drain was placed, yielding purulent necrotic material; cytologically, only neutrophils were identified. However, purulent drainage continued for 28 days without resolution, prompting splenectomy. Pathological dissection revealed a multinodular mass with central necrosis. Microscopic examination revealed extensive karyorrhexis, abundant ghosts of large cells, and scattered large cells with pleomorphic, multilobated, and vesicular nuclei with moderately abundant cytoplasm. Immunohistochemical staining revealed large, atypical cells positive for CD20, CD30, CD45, PAX5, MYC (>40%), MUM1 (>30%), and p53 (focally). The large cells were negative for CD3 (polyclonal), CD4, CD5, CD8, CD10, CD15, CD34, BCL2, BCL6, AE1/AE3, S100, HHV8, and ALK. The Ki‐67 proliferation rate was approximately 80% in large cells. Notably, this PS‐DLBCL was positive for CD30, an unusual finding among non‐Hodgkin B‐cell lymphomas, which, coupled with the Reed‐Sternberg‐like morphology, raised the possibility of classic Hodgkin lymphoma. Therefore, we reviewed the literature to confirm the unique features of this large B‐cell lymphoma, its abscess‐like appearance, and its expression of CD30.

Abstract An essential goal in conservation biology is delineating population units that maximize the probability of species persisting into the future and adapting to future environmental change. However, future‐facing conservation concerns are often addressed using retrospective patterns that could be irrelevant. We recommend a novel landscape genomics framework for delineating future “Geminate Evolutionary Units” (GEUs) in a focal species: (1) identify loci under environmental selection, (2) model and map adaptive conservation units that may spawn future lineages, (3) forecast relative selection pressures on each future lineage, and (4) estimate their fitness and likelihood of persistence using geo‐genomic simulations. Using this process, we delineated conservation units for the Yosemite toad (Anaxyrus canorus), a U.S. federally threatened species that is highly vulnerable to climate change. We used a genome‐wide dataset, redundancy analysis, and Bayesian association methods to identify 24 candidate loci responding to climatic selection (R2 ranging from 0.09 to 0.52), after controlling for demographic structure. Candidate loci included genes such as MAP3K5, involved in cellular response to environmental change. We then forecasted future genomic response to climate change using the multivariate machine learning algorithm Gradient Forests. Based on all available evidence, we found three GEUs in Yosemite National Park, reflecting contrasting adaptive optima: YF‐North (high winter snowpack with moderate summer rainfall), YF‐East (low to moderate snowpack with high summer rainfall), and YF‐Low‐Elevation (low snowpack and rainfall). Simulations under the RCP 8.5 climate change scenario suggest that the species will decline by 29% over 90 years, but the highly diverse YF‐East lineage will be least impacted for two reasons: (1) geographically it will be sheltered from the largest climatic selection pressures, and (2) its standing genetic diversity will promote a faster adaptive response. Our approach provides a comprehensive strategy for protecting imperiled non‐model species with genomic data alone and has wide applicability to other declining species.

Abstract Evolutionary theory predicts that the process of range expansion will lead to differences in life‐history and dispersal traits between the core and edge of a population. At the edge, selection and genetic drift can have opposing effects on reproductive ability, while spatial sorting by dispersal ability can increase dispersal. However, the context that individuals experience, including population density and mating status, also impacts dispersal behavior. We seek to understand the shifts in traits of populations expanding across natural, heterogenous environments, and the evolutionary and behavioral factors that may drive those shifts. We evaluated theoretical predictions for evolution of reproductive life‐history and dispersal traits using the range expansion of a biological control agent, Diorhabda carinulata, or northern tamarisk beetle. We find that individuals from the edge had increased fecundity and female body mass, and reduced age at first reproduction, indicating that genetic load is low and suggesting that selection has acted at the edge. We also find that density of conspecifics during rearing and mating status influence dispersal of males and that dispersal increases at the edge of the range under certain conditions, particularly when males were unmated and reared at low density. The restricted conditions in which dispersal has increased suggest that spatial sorting has exerted weak effects relative to other potential processes. Our results support most theoretical predictions about evolution during range expansion, even across a heterogeneous environment, especially when the ecological context is considered.

Background There is a need to develop electronic health record–based predictive models for worsening heart failure (WHF) events across clinical settings and across the spectrum of left ventricular ejection fraction (LVEF). Methods and Results We studied adults with heart failure (HF) from 2011 to 2019 within an integrated health care delivery system. WHF encounters were ascertained using natural language processing and structured data. We conducted boosted decision tree ensemble models to predict 1‐year hospitalizations, emergency department visits/observation stays, and outpatient encounters for WHF and all‐cause death within each LVEF category: HF with reduced ejection fraction (EF) (LVEF

Abstract The impacts of stratospheric ozone recovery on Southern Ocean surface and interior temperature, heat content, heat uptake, and heat transport are investigated by contrasting two ensemble chemistry‐climate model simulations in 2005–2099: one with fixed ozone depleting substances (ODSs) and another with decreasing ODSs. In our simulations ozone recovery significantly affects Southern Ocean temperature, with large latitudinal and vertical variations. Ozone recovery causes a dipole change of the full‐depth ocean heat content (OHC) with an increase south of 60°S and a decrease between 45°S and 60°S. Integrated over latitudes south of 40°S, OHC decreases in response to ozone recovery. This ocean heat loss is shown to be driven by weakened poleward ocean heat transport (OHT) across 40°S, which is partly canceled by enhanced heat uptake. The weakening of poleward OHT into the Southern Ocean is caused by the ozone‐induced equatorward shift of the meridional overturning circulation.

Abstract Sorghum is an essential crop for resilient and adaptive responses to climate change. The root systems of crop plants significantly contribute to the tolerance of abiotic stresses. There is little information on sorghum genotypes' root systems and plasticity to external P supply. In this paper, we investigated the variations in root systems, as well as the responses, trait relationships, and plasticity of two sorghum genotypes (Naga Red and Naga White), popularly grown in Ghana, to five external P concentrations ([P]ext): 0, 100, 200, 300, and 400 mg P kg−1 soil. Sorghum plants were grown in greenhouse pots and harvested for root trait measurements at the five‐leaf and growing point differentiation (GPD) developmental stages. The plants were responsive to [P]ext and formed rhizosheaths. The two genotypes showed similar characteristics for most of the traits measured but differed significantly in total and lateral root lengths in favor of the red genotype. For example, at the five‐leaf growth stage, the lateral root length of the red and white genotypes was 22.8 and 16.2 cm, respectively, but 124 and 88.9 cm, at the GPD stage. The responses and plasticity of the root system traits, including rhizosheath, to [P]ext were more prominent, positive, and linear at the five‐leaf stage than at the GPD growth stage. At the five‐leaf growth stage, total root length increased by about 2.5‐fold with increasing [P]ext compared to the unamended soil. At the GPD stage, however, total root length decreased by about 1.83‐fold as [P]ext increased compared to the unamended soil. Specific rhizosheath weight correlated with RHD, albeit weakly, and together explained up to 59% of the variation in tissue P. Root hair density was more responsive to P supply than root hair length and showed a similar total and lateral root length pattern. Most desirable responses to P occurred at a rate of 200–300 mg P kg−1 soil. It is concluded that sorghum would form rhizosheath, and [P]ext could be critical for the early vigorous growth of sorghum's responsive root and shoot traits. Beyond the early days of development, additional P application might be necessary to sustain the responses and plasticity observed during the early growth period, but this requires further investigation, potentially under field conditions.

Abstract Within clinical, biomedical, and translational science, an increasing number of projects are adopting graphs for knowledge representation. Graph‐based data models elucidate the interconnectedness among core biomedical concepts, enable data structures to be easily updated, and support intuitive queries, visualizations, and inference algorithms. However, knowledge discovery across these “knowledge graphs” (KGs) has remained difficult. Data set heterogeneity and complexity; the proliferation of ad hoc data formats; poor compliance with guidelines on findability, accessibility, interoperability, and reusability; and, in particular, the lack of a universally accepted, open‐access model for standardization across biomedical KGs has left the task of reconciling data sources to downstream consumers. Biolink Model is an open‐source data model that can be used to formalize the relationships between data structures in translational science. It incorporates object‐oriented classification and graph‐oriented features. The core of the model is a set of hierarchical, interconnected classes (or categories) and relationships between them (or predicates) representing biomedical entities such as gene, disease, chemical, anatomic structure, and phenotype. The model provides class and edge attributes and associations that guide how entities should relate to one another. Here, we highlight the need for a standardized data model for KGs, describe Biolink Model, and compare it with other models. We demonstrate the utility of Biolink Model in various initiatives, including the Biomedical Data Translator Consortium and the Monarch Initiative, and show how it has supported easier integration and interoperability of biomedical KGs, bringing together knowledge from multiple sources and helping to realize the goals of translational science.

Abstract Madagascar exhibits exceptionally high levels of biodiversity and endemism. Models to explain the diversification and distribution of species in Madagascar stress the importance of historical variability in climate conditions which may have led to the formation of geographic barriers by changing water and habitat availability. The relative importance of these models for the diversification of the various forest‐adapted taxa of Madagascar has yet to be understood. Here, we reconstructed the phylogeographic history of Gerp's mouse lemur (Microcebus gerpi) to identify relevant mechanisms and drivers of diversification in Madagascar's humid rainforests. We used restriction site associated DNA (RAD) markers and applied population genomic and coalescent‐based techniques to estimate genetic diversity, population structure, gene flow and divergence times among M. gerpi populations and its two sister species M. jollyae and M. marohita. Genomic results were complemented with ecological niche models to better understand the relative barrier function of rivers and altitude. We show that M. gerpi diversified during the late Pleistocene. The inferred ecological niche, patterns of gene flow and genetic differentiation in M. gerpi suggest that the potential for rivers to act as biogeographic barriers depended on both size and elevation of headwaters. Populations on opposite sides of the largest river in the area with headwaters that extend far into the highlands show particularly high genetic differentiation, whereas rivers with lower elevation headwaters have weaker barrier functions, indicated by higher migration rates and admixture. We conclude that M. gerpi likely diversified through repeated cycles of dispersal punctuated by isolation to refugia as a result of paleoclimatic fluctuations during the Pleistocene. We argue that this diversification scenario serves as a model of diversification for other rainforest taxa that are similarly limited by geographic factors. In addition, we highlight conservation implications for this critically endangered species, which faces extreme habitat loss and fragmentation.

Abstract An analysis is made of geophysical records of the 24 March 1940, magnetic storm and related reports of interference on long‐line communication and power systems across the contiguous United States and, to a lesser extent, Canada. Most long‐line system interference occurred during local daytime, after the second of two storm sudden commencements and during the early part of the storm's main phase. The high degree of system interference experienced during this storm is inferred to have been due to unusually large‐amplitude and unusually rapid geomagnetic field variation, possibly driven by interacting interplanetary coronal‐mass ejections. Geomagnetic field variation, in turn, induced geoelectric fields in the electrically conducting solid Earth, establishing large potential differences (voltages) between grounding points at communication depots and transformer substations connected by long transmission lines. It is shown that March 1940 storm‐time communication‐ and power‐system interference was primarily experienced over regions of high electromagnetic surface impedance, mainly in the upper Midwest and eastern United States. Potential differences measured on several grounded long lines during the storm exceeded 1‐min resolution voltages that would have been induced by the March 1989 storm. In some places, voltages exceeded American electric‐power‐industry benchmarks. It is concluded that the March 1940 magnetic storm was unusually effective at inducing geoelectric fields. Although modern communication systems are now much less dependent on long electrically conducting transmission lines, modern electric‐power‐transmission systems are more dependent on such lines, and they, thus, might experience interference with the future occurrence of a storm as effective as that of March 1940.

Abstract Evaporation is controlled by soil moisture (SM) availability when conditions are not extremely wet. In such a moisture‐limited regime, land‐atmosphere coupling is active, and a chain of linked processes allow land surface anomalies to affect weather and climate. How frequently any location is in a moisture‐limited regime largely determines the intensity of land feedbacks on climate. Conventionally this has been quantified by shifting probability distributions of SM, but the boundary between moisture‐limited and energy‐limited regimes, called the critical soil moisture (CSM) value, can also change. CSM is an emergent property of the land‐atmosphere system, determined by the balance of radiative, thermal and kinetic energy factors. We propose a novel framework to separate the contributions of these separate effects on the likelihood that SM lies in the moisture‐limited regime. We confirm that global warming leads to a more moisture‐limited world. This is attributed to reduced SM in most regions: the moisture effect. CSM changes mainly due to shifts in the surface energy budget, significantly affecting 27.7% of the globe in analyzed climate change simulations. However, consistency among Earth system models regarding CSM change is low. The poor agreement hints that variability of CSM in models and the factors that determine CSM are not well represented. The fidelity of CSM in Earth system models has been overlooked as a factor in water cycle projections. Careful assessment of CSM in nature and for model development should be a priority, with potential benefits for multiple research fields including meteorology, hydrology, and ecology.

Abstract Background and Aims Adequate postoperative analgesia and prevention of post‐op nausea and vomiting (PONV) are core components of modern day anaesthesia and peri‐operative care. As well as contributing to overall morbidity, postoperative pain and PONV are frequently cited as one of the most unpleasant and distressing aspects of surgery for patients. Variation in healthcare delivery is known to exist but has often been poorly described. A first step to understanding the consequences of variation is to describe the extent of variation. We aimed to assess variation in pharmacological strategies to prevent postoperative pain, nausea and vomiting in patients undergoing elective major abdominal surgery at a tertiary hospital in Perth, Western Australia, over a three‐month period. Methods Retrospective cross‐sectional study. Results We observed considerable variation in prescribing of postoperative analgesia and PONV prophylaxis and suggest that despite adequate evidence based guidelines, they are often overlooked in practice. Conclusion Measurement of the consequences of variation requires randomised clinical trials that evaluate differences in outcome and cost, associated with the strategies that exist within the spectrum of variation.

Recent advances in wearable technology through convenient and cuffless systems will enable continuous, noninvasive monitoring of blood pressure (BP), heart rate, and heart rhythm on both longitudinal 24‐hour measurement scales and high‐frequency beat‐to‐beat BP variability and synchronous heart rate variability and changes in underlying heart rhythm. Clinically, BP variability is classified into 4 main types on the basis of the duration of monitoring time: very‐short‐term (beat to beat), short‐term (within 24 hours), medium‐term (within days), and long‐term (over months and years). BP variability is a strong risk factor for cardiovascular diseases, chronic kidney disease, cognitive decline, and mental illness. The diagnostic and therapeutic value of measuring and controlling BP variability may offer critical targets in addition to lowering mean BP in hypertensive populations.

Abstract This research assesses the influences of Atlantic Multidecadal Variability (AMV) on global tropical cyclones (TCs) using two large ensembles of idealized global climate model simulations with opposite signs of AMV forcings superimposed (i.e., AMV+ and AMV–). We first detect TCs and then compare TC activity by basin in the two AMV experiments. We find contrasting responses of Atlantic and Pacific TC frequency to the AMV anomalies. Compared to AMV–, AMV+ significantly increases TC frequency in the North Atlantic, including those making landfalls. The increase is explained by warmer sea surface temperature, higher relative humidity, increased relative vorticity, and weaker vertical wind shear under AMV+. By contrast, AMV+ decreases TC occurrence over the western North Pacific and South Pacific, which is tied to stronger vertical wind shear and lower relative humidity. The opposite responses of TC activity to AMV+ are attributed to strengthened Walker Circulation between the Atlantic and Pacific.

Abstract Background Skeletomuscular diseases result in significant muscle loss and decreased performance, paralleled by a loss in mitochondrial and oxidative capacity. Insulin and insulin‐like growth factor‐1 (IGF‐1) are two potent anabolic hormones that activate a host of signalling intermediates including the serine/threonine kinase AKT to influence skeletal muscle physiology. Defective AKT signalling is associated with muscle pathology, including cachexia, sarcopenia, and disuse; however, the mechanistic underpinnings remain unresolved. Methods To elucidate the role of AKT signalling in muscle mass and physiology, we generated both congenital and inducible mouse models of skeletal muscle‐specific AKT deficiency. To understand the downstream mechanisms mediating AKT's effects on muscle biology, we generated mice lacking AKT1/2 and FOXO1 (M‐AKTFOXO1TKO and M‐indAKTFOXO1TKO) to inhibit downstream FOXO1 signalling, AKT1/2 and TSC1 (M‐AKTTSCTKO and M‐indAKTTSCTKO) to activate mTORC1, and AKT1/2, FOXO1, and TSC1 (M‐QKO and M‐indQKO) to simultaneously activate mTORC1 and inhibit FOXO1 in AKT‐deficient skeletal muscle. Muscle proteostasis and physiology were assessed using multiple assays including metabolic labelling, mitochondrial function, fibre typing, ex vivo physiology, and exercise performance. Results Here, we show that genetic ablation of skeletal muscle AKT signalling resulted in decreased muscle mass and a loss of oxidative metabolism and muscle performance. Specifically, deletion of muscle AKT activity during development or in adult mice resulted in a significant reduction in muscle growth by 30–40% (P

Background Larger within‐patient variability of lipid levels has been associated with increased risk of cardiovascular disease (CVD); however, measures of lipid variability require ≥3 measurements and are not currently used clinically. We investigated the feasibility of calculating lipid variability within a large electronic health record–based population cohort and assessed associations with incident CVD. Methods and Results We identified all individuals ≥40 years of age who resided in Olmsted County, MN, on January 1, 2006 (index date), without prior CVD, defined as myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention, or CVD death. Patients with ≥3 measurements of total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, or triglycerides during the 5 years before the index date were retained. Lipid variability was calculated using variability independent of the mean. Patients were followed through December 31, 2020 for incident CVD. We identified 19 652 individuals (mean age 61 years; 55% female), who were CVD‐free and had variability independent of the mean calculated for at least 1 lipid type. After adjustment, those with highest total cholesterol variability had a 20% increased risk of CVD (Q5 versus Q1 hazard ratio, 1.20 [95% CI, 1.06–1.37]). Results were similar for low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol. Conclusions In a large electronic health record–based population cohort, high variability in total cholesterol, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol was associated with an increased risk of CVD, independent of traditional risk factors, suggesting it may be a possible risk marker and target for intervention. Lipid variability can be calculated in the electronic health record environment, but more research is needed to determine its clinical utility.

Background Oral anticoagulation reduces stroke and disability in atrial fibrillation (AF) but is underused. We evaluated the effects of a novel patient‐clinician shared decision‐making (SDM) tool in reducing oral anticoagulation patient's decisional conflict as compared with usual care. Methods and Results We designed and evaluated a new digital decision aid in a multicenter, randomized, comparative effectiveness trial, ENHANCE‐AF (Engaging Patients to Help Achieve Increased Patient Choice and Engagement for AF Stroke Prevention). The digital AF shared decision‐making toolkit was developed using patient‐centered design with clear health communication principles (eg, meaningful images, limited text). Available in English and Spanish, the toolkit included the following: (1) a brief animated video; (2) interactive questions with answers; (3) a quiz to check on understanding; (4) a worksheet to be used by the patient during the encounter; and (5) an online guide for clinicians. The study population included English or Spanish speakers with nonvalvular AF and a CHA2DS2‐VASc stroke score ≥1 for men or ≥2 for women. Participants were randomized in a 1:1 ratio to either usual care or the shared decision‐making toolkit. The primary end point was the validated 16‐item Decision Conflict Scale at 1 month. Secondary outcomes included Decision Conflict Scale at 6 months and the 10‐item Decision Regret Scale at 1 and 6 months as well as a weighted average of Mann–Whitney U‐statistics for both the Decision Conflict Scale and the Decision Regret Scale. A total of 1001 participants were enrolled and followed at 5 different sites in the United States between December 18, 2019, and August 17, 2022. The mean patient age was 69±10 years (40% women, 16.9% Black, 4.5% Hispanic, 3.6% Asian), and 50% of participants had CHA2DS2‐VASc scores ≥3 (men) or ≥4 (women). The primary end point at 1 month showed a clinically meaningful reduction in decisional conflict: a 7‐point difference in median scores between the 2 arms (16.4 versus 9.4; Mann–Whitney U‐statistics=0.550; P=0.007). For the secondary end point of 1‐month Decision Regret Scale, the difference in median scores between arms was 5 points in the direction of less decisional regret (P=0.078). The treatment effects lessened over time: at 6 months the difference in medians was 4.7 points for Decision Conflict Scale (P=0.060) and 0 points for Decision Regret Scale (P=0.35). Conclusions Implementation of a novel shared decision‐making toolkit (afibguide.com; afibguide.com/clinician) achieved significantly lower decisional conflict compared with usual care in patients with AF. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096781.

Abstract Liriomyza sativae, the vegetable leafminer, is an important agricultural pest originally from the Americas, which has now colonized all continents except Antarctica. In 2015, L. sativae arrived on the Australian mainland and established on the Cape York Peninsula in the northeast of the country near the Torres Strait, which provides a possible pathway for pests to enter Australia and evade biosecurity efforts. Here, we assessed genetic variation in L. sativae based on genome‐wide single nucleotide polymorphisms (SNPs) generated by double digest restriction‐site‐associated DNA sequencing (ddRAD‐seq), aiming to uncover the potential origin(s) of this pest in Australia and contribute to reconstructing its global invasion history. Our fineRADstructure results and principal component analysis suggest Australian mainland populations were genetically close to populations from the Torres Strait, whereas populations from Asia, Africa, and Papua New Guinea (PNG) were more distantly related. Hawaiian populations were genetically distinct from all other populations of L. sativae included in our study. Admixture analyses further revealed that L. sativae from the Torres Strait may have genetic variation originating from multiple sources including Indonesia and PNG, and which has now spread to the Australian mainland. The L. sativae lineages from Asia and Africa appear closely related. Isolation‐by‐distance (IBD) was found at a broad global scale, but not within small regions, suggesting that human‐mediated factors likely contribute to the local spread of this pest. Overall, our findings suggest that an exotic Liriomyza pest invaded Australia through the Indo‐Papuan conduit, highlighting the importance of biosecurity programs aimed at restricting the movement of pests and diseases through this corridor.

Abstract Similar to other causes of acute respiratory distress syndrome, coronavirus disease 2019 (COVID‐19) is characterized by the aberrant expression of vascular injury biomarkers. We present the first report that circulating plasma bone morphogenetic proteins (BMPs), BMP9 and pBMP10, involved in vascular protection, are reduced in hospitalized patients with COVID‐19.