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Abstract Identification of the geographic origin of invasive species can be critical to effective management and amelioration of negative impacts in the introduced range. Liriomyza huidobrensis is a polyphagous leafmining fly that is a devastating pest of many vegetable and floriculture crops around the world. Considered native to South and possibly Central America, L. huidobrensis became invasive in the 1980s and has since spread to at least 30 countries on five continents. We used phylogeographic analysis of over 2 kb of mitochondrial cytochrome oxidase I and II sequence data from 403 field‐collected specimens from both native and introduced populations to investigate the geographic origins of invasive L. huidobrensis worldwide. Within South America, there was substantial genetic variation, as well as the strong phylogeographic structure typical of a native range. In contrast, leafminers from the introduced range and Central America all contained little genetic variation and shared the same small set of haplotypes. These haplotypes trace to Peru as the ultimate geographic origin of invasive populations. Central America is rejected as part of the original geographic range of L. huidobrensis. Within Peru, the primary export region of Lima shared an extremely similar pattern of reduced haplotype variation to the invasive populations. An additional 18 specimens collected at US ports of entry did not share the same haplotype profile as contemporary invasive populations, raising perplexing questions on global pathways and establishment success in this species.

Abstract ‘Early detection and rapid response’ (EDRR) is the most successful framework for preventative invasive species management, but prioritizing localized EDRR actions with limited resources is challenging. An approach that ranks individual locations, such as waterbodies, for EDRR by combining an invasive species' establishment risk with the practicality of managing it could help set reasonable priorities. Here, we worked with regional practitioners in Arkansas, USA, and the broader Southeastern USA to co‐produce a workflow for preventative aquatic invasive species management that (1) estimates establishment risk under current and future climates with a species distribution model, (2) scores waterbodies according to difficulty of eradicating an aquatic invasive species if it were introduced and (3) combines establishment risk and eradication difficulty scores to rank waterbodies according to preventative management priority. As our focal species, we used giant salvinia (Salvinia molesta), a floating aquatic fern ranked among the worst weeds in the world due to its negative socio‐ecological impacts and difficulty to eradicate once established. Current establishment risk is low for much of our study area, but under future climate scenarios (RCP 8.5), areas with >60% giant salvinia establishment risk increased from 546 km2 to 30,219 km2 between 2023 and 2040 in Arkansas. We found giant salvinia establishment risk and eradication difficulty are independent of each other (r = 0.28), and it follows that, alone, early detection tools such as species distribution models are insufficient for managers to prioritize sites for EDRR. Practical implication: We envision our approach fitting into a potential EDRR workflow that cascades from broad‐ to local‐scale. To illustrate, (1) horizon scanning and/or climate matching generates lists of high‐risk invasive species; (2) species lists are narrowed according to eradication feasibility scores; (3) for all remaining species, all waterbodies across a geography of interest receive prioritization rankings based on establishment risk and eradication difficulty scores. Given that climate change makes predicting invasive species' distributions a moving target, combining co‐produced eradication difficulty scoring with species distribution modelling will balance rigour with practicality when prioritizing locations for EDRR.

Background Type 2 diabetes is prevalent in cardiovascular disease and contributes to excess morbidity and mortality. We sought to investigate the effect of glycemia on functional cardiac improvement, morbidity, and mortality in durable left ventricular assist device (LVAD) recipients. Methods and Results Consecutive patients with an LVAD were prospectively evaluated (n=531). After excluding patients missing pre‐LVAD glycated hemoglobin (HbA1c) measurements or having inadequate post‐LVAD follow‐up, 375 patients were studied. To assess functional cardiac improvement, we used absolute left ventricular ejection fraction change (ΔLVEF: LVEF post‐LVAD−LVEF pre‐LVAD). We quantified the association of pre‐LVAD HbA1c with ΔLVEF as the primary outcome, and all‐cause mortality and LVAD‐related adverse event rates (ischemic stroke/transient ischemic attack, intracerebral hemorrhage, gastrointestinal bleeding, LVAD‐related infection, device thrombosis) as secondary outcomes. Last, we assessed HbA1c differences pre‐ and post‐LVAD. Patients with type 2 diabetes were older, more likely men suffering ischemic cardiomyopathy, and had longer heart failure duration. Pre‐LVAD HbA1c was inversely associated with ΔLVEF in patients with nonischemic cardiomyopathy but not in those with ischemic cardiomyopathy, after adjusting for age, sex, heart failure duration, and left ventricular end‐diastolic diameter. Pre‐LVAD HbA1c was not associated with all‐cause mortality, but higher pre‐LVAD HbA1c was shown to increase the risk of intracerebral hemorrhage, LVAD‐related infection, and device thrombosis by 3 years on LVAD support (P

Abstract Seismic observations show the Earth's inner core has significant and unexplained variation in seismic attenuation with position, depth and direction. Interpreting these observations is difficult without knowledge of the visco‐ or anelastic dissipation processes active in iron under inner core conditions. Here, a previously unconsidered attenuation mechanism is observed in zinc, a low pressure analog of hcp‐iron, during small strain sinusoidal deformation experiments. The experiments were performed in a deformation‐DIA combined with X‐radiography, at seismic frequencies (∼0.003–0.1 Hz), high pressure and temperatures up to ∼80% of melting temperature. Significant dissipation (0.077 ≤ Q−1(ω) ≤ 0.488) is observed along with frequency dependent softening of zinc's Young's modulus and an extremely small activation energy for creep (⩽7 kJ mol−1). In addition, during sinusoidal deformation the original microstructure is replaced by one with a reduced dislocation density and small, uniform, grain size. This combination of behavior collectively reflects a mode of deformation called “internal stress superplasticity”; this deformation mechanism is unique to anisotropic materials and activated by cyclic loading generating large internal stresses. Here we observe a new form of internal stress superplasticity, which we name as “elastic strain mismatch superplasticity.” In it the large stresses are caused by the compressional anisotropy. If this mechanism is also active in hcp‐iron and the Earth's inner‐core it will be a contributor to inner‐core observed seismic attenuation and constrain the maximum inner‐core grain‐size to ≲10 km.

Abstract Body size is a fundamental biological trait shaping ecological interactions, evolutionary processes, and our understanding of the structure and dynamics of marine communities on a global scale. Accurately defining a species' body size, despite the ease of measurement, poses significant challenges due to varied methodologies, tool usage, and subjectivity among researchers, resulting in multiple, often discrepant size estimates. These discrepancies, stemming from diverse measurement approaches and inherent variability, could substantially impact the reliability and precision of ecological and evolutionary studies reliant on body size data across extensive species datasets. This study examines the variation in reported maximum body sizes across 69,570 individual measurements of maximum size, ranging from 45 m, for 27,271 species of marine metazoans. The research aims to investigate how reported maximum size variations within species relate to organism size, taxonomy, habitat, and the presence of skeletal structures. The investigation particularly focuses on understanding why discrepancies in maximum size estimates arise and their potential implications for broader ecological and evolutionary studies relying on body size data. Variation in reported maximum sizes is zero for 38% of species, and low for most species, although it exceeds two orders of magnitude for some species. The likelihood of zero variation in maximum size decreased with more measurements and increased in larger species, though this varied across phyla and habitats. Pelagic organisms consistently had low maximum size range values, while small species with unspecified habitats had the highest variation. Variations in maximum size within a species were notably smaller than interspecific variation at higher taxonomic levels. Significant variation in maximum size estimates exists within marine species, and partially explained by organism size, taxonomic group, and habitat. Variation in maximum size could be reduced by standardized measurement protocols and improved meta‐data. Despite the variation, egregious errors in published maximum size measurements are rare, and their impact on comparative macroecological and macroevolutionary research is likely minimal.

Abstract Objective Telehealth evaluation of hearing is rapidly evolving; however, the lack of consensus on the most accurate remote hearing test application has made hearing evaluation complicated. The objective of this study was to evaluate the correlation between the pure tone audiometry results obtained from app‐based hearing testing programs and a traditional audiogram. Methods A prospective within‐subject and between‐subject study design was used to correlate audiogram results between app‐based hearing programs and a traditional audiogram. All participants completed a traditional audiogram, 1 commercial app‐based test (ShoeBox), 2 consumer app‐based tests (EarTrumpet and Hearing Test and Ear Age Test [HTEAT]), and a Hearing Handicap Inventory screening version (HHI‐S). Testing was conducted in an acoustically controlled environment (traditional) and a quiet room (app‐based hearing tests). Results A total of 39 participants were enrolled in the study (21 with normal hearing and 18 with hearing loss). In patients with normal hearing, only the commercial hearing testing app (ShoeBox) had a statistically significant pure tone average correlation in both ears with traditional audiometry (Right ear—r = 0.7, p = .005, Left ear—r = 0.66, p = .001). Both consumer and commercial apps had statistically significant correlations with both ears in patients with hearing loss (ranging from r = 0.62 to r = 0.9). Regarding accuracy within 10 dB of the pure tone average of the traditional audiogram of all tested ears, the commercial app‐based test was accurate in 94% for all ears (normal and hearing loss), while consumer app‐based tests were between 14% and 36% for all ears. The HHI‐S indicated no hearing impairment in 95% of those with normal hearing and indicated hearing impairment in 89% of those with hearing loss. Conclusion Commercial‐grade app‐based pure tone audiometry demonstrates overall strong correlation and accuracy with traditional audiometry. The HHI‐S assessment remains a valid and useful tool to predict normal hearing and hearing impairment. Level of Evidence 2

Abstract Effective antiviral treatments for coronavirus disease 2019 (COVID‐19) are needed to reduce the morbidity and mortality associated with severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection, particularly in patients with risk factors for severe disease. Molnupiravir (MK‐4482, EIDD‐2801) is an orally administered, ribonucleoside prodrug of β‐D‐N4‐hydroxycytidine (NHC) with submicromolar potency against SARS‐CoV‐2. A population pharmacokinetic (PopPK) analysis for molnupiravir exposure was conducted using 4202 NHC plasma concentrations collected in 1207 individuals from a phase I trial in healthy participants, a phase IIa trial in non‐hospitalized participants with COVID‐19, a phase II trial in hospitalized participants with COVID‐19, and a phase II/III trial in non‐hospitalized participants with COVID‐19. Molnupiravir pharmacokinetics (PK) was best described by a two‐compartment model with a transit‐compartment absorption model and linear elimination. Molnupiravir apparent elimination clearance increased with body weight less‐than‐proportionally (power 0.412) and was estimated as 70.6 L/h in 80‐kg individuals with a moderate interindividual variability (43.4% coefficient of variation). Additionally, effects of sex and body mass index on apparent central volume and food status and formulation on the absorption mean transit time were identified as statistically significant descriptors of variability in these PK parameters. However, none of the identified covariate effects caused clinically relevant changes in the area under the NHC concentration versus time curve between doses, the exposure metric most closely related to clinical response. Overall, the PopPK model indicates that molnupiravir can be administered in adults without dose adjustment based on age, sex, body size, food, and mild‐to‐moderate renal or mild hepatic impairment.

Abstract Identifying the most important factors affecting population growth in animal life cycles is an important tool of species conservation. Delta Smelt (Hypomesus transpacificus), an annual fish endemic to the San Francisco Estuary in California (USA), has been provided legal protection since 1993 but 30 years later exists in a conservation‐reliant state on the brink of extinction. Despite considerable controversies about what factors are most responsible for the species' decline, no population growth rate sensitivity comparisons between the most important factors regulating growth have been done. Nor has anyone attempted to quantitatively identify habitat conditions needed to support positive population growth. We developed a set of stage‐structured population models to link habitat indices regulating recruitment of new generations of fish as they metamorphosed into juveniles and the subsequent survival of those fish over several seasons until they reached adulthood. These models are used to quantify drivers of growth rate variation over 30 years. Several complimentary sensitivity analyses indicated freshwater outflow to the estuary during summer had the largest potential to change population growth. Multiple habitat metrics (e.g., food availability, temperature) influencing recruitment and life stage specific survival rates across different seasons interacted in nonlinear ways to determine habitat conditions and water management targets associated with positive population growth. We discuss the implications for freshwater management, Delta Smelt conservation, and the challenges climate change poses for co‐implementation of these two societal priorities.

Background Hypertension is a stroke risk factor with known disparities in prevalence and management between Black and White patients. We sought to identify if racial differences in presenting blood pressure (BP) during acute ischemic stroke exist. Methods and Results Adults with acute ischemic stroke presenting to an emergency department within 24 hours of last known normal during study epochs 2005, 2010, and 2015 within the Greater Cincinnati/Northern Kentucky Stroke Study were included. Demographics, histories, arrival BP, National Institutes of Health Stroke Scale score, and time from last known normal were collected. Multivariable linear regression was used to determine differences in mean BP between Black and White patients, adjusting for age, sex, National Institutes of Health Stroke Scale score, history of hypertension, hyperlipidemia, smoking, stroke, body mass index, and study epoch. Of 4048 patients, 853 Black and 3195 White patients were included. In adjusted analysis, Black patients had higher presenting systolic BP (161 mm Hg [95% CI, 159–164] versus 158 mm Hg [95% CI, 157–159], P

Abstract Objectives Online educational platforms with open access have seen a growing adoption in the field of medical education. However, the extent of their global usage is still unclear. To fill this knowledge gap, our objective is to examine the usage patterns of two renowned open‐access resources in Otolaryngology. This includes identifying the most sought‐after topics and understanding the demographics of their users. Methods Retrospective study of web analytics data between 2016 and 2021 extracted from the Headmirror.com and Mayo Clinic Otolaryngology YouTube channel platforms analyzing demographic and education topic trends via descriptive, geospatial, time‐series, t‐tests, and ANOVA analyses. Results Viewership spanned 124 countries in 7 different geographic regions, with 72 countries comprising low‐ to middle‐income countries, mostly represented ages of 25–34 years old, came from high‐income countries rather than low‐income (p

Abstract Background Many dog owners alter their dog's nutritional regimen after a diagnosis of cancer. There are limited data as to specific changes made and reasons behind these changes. Hypothesis/Objectives To collect updated and detailed data on changes made by owners to their dog's diet and supplements after a cancer diagnosis. Animals Responses were collected from a survey of dog owners who brought their dogs to the UC Davis Veterinary Medical Teaching Hospital's Oncology Service for the first time after a cancer diagnosis. Dogs with recurrence or presenting for a second type of cancer were excluded. Methods Eligible owners were surveyed between December 2020 and March 2022. The survey contained 62 questions regarding diet, supplement use, and treats, and how these were altered after a cancer diagnosis. Responses were matched to medical record data. Results One hundred twenty‐eight surveys were retained for analysis, including 120 respondents that completed the survey. In response to a cancer diagnosis, 54.8% (95% CI; 45.7%‐63.8%) of owners altered diets or supplements or both. The most common informational resource for dog diets was veterinarians (53.9%). Usage of home‐prepared foods significantly increased after a cancer diagnosis (P = .03). There was no significant difference in commercial diet usage before or after a diagnosis (P = .25). Joint support products were the most common supplements given both before (37.4%) and after (35.0%) diagnosis. Conclusions and Clinical Importance Many dog owners alter their dog's nutritional intake after a cancer diagnosis. These owners should be provided information relating to commonly observed alterations, including home‐prepared foods and supplements.

Abstract Objectives Investigate opioid usage and postoperative pain in patients undergoing head and neck free flap surgery. Methods A retrospective review of 100 consecutive patients undergoing head and neck free flap reconstruction at two academic centers was performed. Data captured included demographics, postoperative inpatient pain, pain at postoperative visits, morphine equivalent doses (MEDs) administration, medication history, and comorbidities. Data were analyzed using regression models, χ2 tests, and student's t‐tests. Results Seventy‐three percent of patients were discharged with opioid medication, with over half (53.4%) continuing to take opioids at their second postoperative visit, and over one‐third (34.2%) continuing to take them around 4‐month postoperatively. One out of every five (20.3%) opioid‐naïve patients chronically took opioids postoperatively. There was a poor association between inpatient postoperative pain scores and daily MEDs administered (R2 = 0.13, 0.17, and 0.22 in postoperative Days 3, 5, and 7, respectively). Neither preoperative radiotherapy nor postoperative complications were associated with an increase in opioid usage. Conclusions For patients undergoing head and neck free flap operations, opioid medications are commonly used for postoperative analgesia. This practice may increase the chance an opioid‐naïve patient uses opioids chronically. We found a poor association between MEDs administered and patient‐reported pain scores, which suggests that standardized protocols aimed at optimizing analgesia while reducing opioid administration may be warranted. Level of Evidence: 3 (Retrospective cohort study).

Abstract Objective Endotracheal intubation is a common procedure in the medical intensive care unit (MICU), but it carries risk of complications including, but not limited to, subglottic stenosis (SGS) and tracheal stenosis (TS). Current literature suggests identifiable risk factors for the development of airway complications. This study is a comprehensive evaluation of potential risk factors in patients who developed SGS and TS following endotracheal intubation in our MICU. Methods Patients intubated in our MICU were identified from 2013 to 2019. Diagnoses of SGS or TS within 1 year of MICU admission were identified. Data extracted included age, sex, body measurements, comorbidities, bronchoscopies, endotracheal tube size, tracheostomy, social history, and medications. Patients with prior diagnosis of airway complication, tracheostomy, or head and neck cancer were excluded. Univariate and multivariate logistic regressions were performed. Results A total of 136 patients with TS or SGS were identified out of a sample of 6603 patients intubated in the MICU. Cases were matched to controls who did not develop airway stenosis based on identical Charlson Comorbidity Index scores. Eighty six controls were identified with a complete record of endotracheal/tracheostomy tube size, airway procedures, sociodemographic data, and medical diagnosis. Regression analysis showed that SGS or TS were associated with tracheostomy, bronchoscopy, chronic obstructive pulmonary disease, current tobacco use, gastroesophageal reflux disease, systemic lupus erythematosus, pneumonia, bronchitis, and numerous medication classes. Conclusion Various conditions, procedures, and medications are associated with an increased risk of developing SGS or TS. Level of evidence 4.

Abstract Molnupiravir is an oral prodrug of the broadly active, antiviral ribonucleoside analog N‐hydroxycytidine (NHC). The primary circulating metabolite NHC is taken up into cells and phosphorylated to NHC‐triphosphate (NHC‐TP). NHC‐TP serves as a competitive substrate for viral RNA‐dependent RNA polymerase (RdRp), which results in an accumulation of errors in the viral genome, rendering virus replication incompetent. Molnupiravir has demonstrated activity against SARS‐CoV‐2 both clinically and preclinically and has a high barrier to development of viral resistance. Little to no molnupiravir is observed in plasma due to rapid hydrolysis to NHC. Maximum concentrations of NHC are reached at 1.5 h following administration in a fasted state. The effective half‐life of NHC is 3.3 h, reflecting minimal accumulation in the plasma following twice‐daily (Q12H) dosing. The terminal half‐life of NHC is 20.6 h. NHC‐TP exhibits a flatter profile with a lower peak‐to‐trough ratio compared with NHC, which supports Q12H dosing. Renal and hepatic pathways are not major routes of elimination, as NHC is primarily cleared by metabolism to uridine and cytidine, which then mix with the endogenous nucleotide pools. In a phase III study of nonhospitalized patients with COVID‐19 (MOVe‐OUT), 5 days of treatment with 800 mg molnupiravir Q12H significantly reduced the incidence of hospitalization or death compared with placebo. Patients treated with molnupiravir also had a greater reduction in SARS‐CoV‐2 viral load and improved clinical outcomes, compared with those receiving placebo. The clinical effectiveness of molnupiravir has been further demonstrated in several real‐world evidence studies. Molnupiravir is currently authorized or approved in more than 25 countries.

Abstract Adaptive divergence in response to environmental clines are expected to be common in species occupying heterogeneous environments. Despite numerous advances in techniques appropriate for non‐model species, gene–environment association studies in elasmobranchs are still scarce. The bronze whaler or copper shark (Carcharhinus brachyurus) is a large coastal shark with a wide distribution and one of the most exploited elasmobranchs in southern Africa. Here, we assessed the distribution of neutral and adaptive genomic diversity in C. brachyurus across a highly heterogeneous environment in southern Africa based on genome‐wide SNPs obtained through a restriction site‐associated DNA method (3RAD). A combination of differentiation‐based genome‐scan (outflank) and genotype–environment analyses (redundancy analysis, latent factor mixed models) identified a total of 234 differentiation‐based outlier and candidate SNPs associated with bioclimatic variables. Analysis of 26,299 putatively neutral SNPs revealed moderate and evenly distributed levels of genomic diversity across sites from the east coast of South Africa to Angola. Multivariate and clustering analyses demonstrated a high degree of gene flow with no significant population structuring among or within ocean basins. In contrast, the putatively adaptive SNPs demonstrated the presence of two clusters and deep divergence between Angola and all other individuals from Namibia and South Africa. These results provide evidence for adaptive divergence in response to a heterogeneous seascape in a large, mobile shark despite high levels of gene flow. These results are expected to inform management strategies and policy at the national and regional level for conservation of C. brachyurus populations.

Background Marijuana leaf vaporizers, which heat plant material and sublimate Δ‐9‐tetrahydrocannabinol without combustion, are popular alternatives to smoking cannabis that are generally perceived to be less harmful. We have shown that smoke from tobacco and marijuana, as well as aerosol from e‐cigarettes and heated tobacco products, impair vascular endothelial function in rats measured as arterial flow‐mediated dilation (FMD). Methods and Results We exposed 8 rats per group to aerosol generated by 2 vaporizer systems (Volcano and handheld Yocan) using marijuana with varying Δ‐9‐tetrahydrocannabinol levels, in a single pulsatile exposure session of 2 s/min over 5 minutes, and measured changes in FMD. To model secondhand exposure, we exposed rats for 1 minute to diluted aerosol approximating release of uninhaled Volcano aerosol into typical residential rooms. Exposure to aerosol from marijuana with and without cannabinoids impaired FMD by ≈50%. FMD was similarly impaired by aerosols from Yocan (237 °C), and from Volcano at both its standard temperature (185 °C) and the minimum sublimation temperature of Δ‐9‐tetrahydrocannabinol (157 °C), although the low‐temperature aerosol condition did not effectively deliver Δ‐9‐tetrahydrocannabinol to the circulation. Modeled secondhand exposure based on diluted Volcano aerosol also impaired FMD. FMD was not affected in rats exposed to clean air or water vapor passed through the Volcano system. Conclusions Acute direct exposure and modeled secondhand exposure to marijuana leaf vaporizer aerosol, regardless of cannabinoid concentration or aerosol generation temperature, impair endothelial function in rats comparably to marijuana smoke. Our findings indicate that use of leaf vaporizers is unlikely to reduce the vascular risk burden of smoking marijuana.

Abstract Effective management of protected species requires information on appropriate evolutionary and geographic population boundaries and knowledge of how the physical environment and life‐history traits combine to shape the population structure and connectivity. Saltwater crocodiles (Crocodylus porosus) are the largest and most widely distributed of living crocodilians, extending from Sri Lanka to Southeast Asia and down to northern Australia. Given the long‐distance movement capabilities reported for C. porosus, management units are hypothesised to be highly connected by migration. However, the magnitude, scale, and consistency of connection across managed populations are not fully understood. Here we used an efficient genotyping method that combines DArTseq and sequence capture to survey ≈3000 high‐quality genome‐wide single nucleotide polymorphisms from 1176 C. porosus sampled across nearly the entire range of the species in Queensland, Australia. We investigated historical and present‐day connectivity patterns using fixation and diversity indices coupled with clustering methods and the spatial distribution of kin pairs. We inferred kinship using forward simulation coupled with a kinship estimation method that is robust to unspecified population structure. The results demonstrated that the C. porosus population has substantial genetic structure with six broad populations correlated with geographical location. The rate of gene flow was highly correlated with spatial distance, with greater differentiation along the east coast compared to the west. Kinship analyses revealed evidence of reproductive philopatry and limited dispersal, with approximately 90% of reported first and second‐degree relatives showing a pairwise distance of

Abstract Tidal marshes and mangroves are threatened by relative sea level rise (RSLR) in certain regions on Earth. Elsewhere, these coastal wetlands can adapt through sediment accretion and resulting surface elevation gain. Studies identifying drivers of the global variability in coastal wetland adaptability to RSLR ignored the role of the tidal pattern, varying from semi‐diurnal to diurnal globally. Here, we present a meta‐analysis, including 394 marsh and mangrove sites worldwide, and demonstrate that the tidal pattern explains ~ 25% of the variability in wetland elevation response to RSLR. Using a numerical model, we illustrate that less frequent, diurnal tides trigger lower sediment accretion rates, hence higher wetland vulnerability to RSLR, for various values of RSLR rates, tidal range and sediment supply. Our findings reveal a previously overlooked but relevant driver of coastal wetland adaptability to RSLR and call for new research as tidal patterns may affect other wetland ecosystem functions and services.

Abstract Mating systems in angiosperms range from obligate outcrossing to highly self‐fertilizing. The belief that obligate selfing does not exist is contradicted by genetic evidence in several populations of L. inflata, in which selfing is enforced by the anthers enclosing the style. However, whether the mating systems of these populations are typical, or an extreme across the species range is unknown. Such trends are hypothesized to result from selection for reproductive assurance under mate limitation at range margins. Here, we use ~7500 iNaturalist community science images, in which stylar exsertion can be observed, to test this hypothesis in L. inflata and, for comparison, in four typical congeneric Lobelias that express a staminate, then a pistillate phase (protandry). Specifically, we analyzed the effects of latitude and range marginality on the frequency of stylar exsertion and number of exserted flowers. Outcrossing capacity in L. inflata increased at low latitudes and near the overall range center, supporting our hypothesis, with exsertion frequencies significantly lower than in congenerics. Interestingly, in outcrossing capable individuals, the number of style‐exserted flowers was consistent across the species range and among species, indicating outcrossing capable L. inflata individuals resemble congenerics. These findings suggest that variation in stylar exsertion is expressed among individuals rather than by all individuals within populations. However, whether this is a result of differences in exsertion allele frequencies or of differentiation in the induction of a threshold trait requires further study. Moreover, the trends in outcrossing capability revealed here imply the potential for geographic variation in L. inflata mating system.

Abstract Pollinators are declining globally, and this loss can reduce plant reproduction, erode critical ecosystem services and resilience, and drive economic losses. Monitoring pollinator biodiversity trends is essential for adaptive conservation and management, but conventional surveys are often costly, time‐consuming, and requires considerable taxonomic expertise. Environmental DNA (eDNA) metabarcoding surveys are booming due to their rapidity, nondestructiveness, and cost efficiency. Microfluidic technology allows multiple primer sets from different markers to be used in eDNA metabarcoding for more comprehensive inventories, minimizing associated primer bias. We evaluated microfluidic eDNA metabarcoding for pollinator community monitoring in both controlled greenhouse and natural field settings. Using a variety of sampling, preservation, and extraction methods, we assessed pollinator communities with a number of markers using microfluidic metabarcoding. In greenhouse experiments, microfluidic eDNA metabarcoding detected the target bumblebee in two of four focal flower species as well as greenhouse insects in all focal flower species. In the field, numerous common regional arthropods, including some directly observed, were detected. Pollinator detection was maximized using whole flower heads preserved in ATL buffer and extracted with a modified Qiagen® DNeasy protocol for amplification with COI primers. eDNA surveillance could enhance pollinator assessment by detecting protected and endangered species and being more applicable to remote, inaccessible locations, whilst reducing survey time, effort, and expense. Microfluidic eDNA metabarcoding requires optimization to address remaining efficacy concerns, but this approach shows potential in revealing complex networks underpinning critical ecosystem functions and services, enabling more accurate assessments of ecosystem resilience.

Abstract Objective To characterize normative adult ranges for cochlear promontory thickness relevant to the development of subendosteal and transpromontory electrodes to rehabilitate various neurotologic disorders. Patients Adults (≥18 years). Intervention In vivo radiologic assessment using a 192‐slice CT scanner (Force‐192; Siemens Healthcare) with ultrahigh‐resolution scan mode combined and iterative reconstruction. Main Outcome Measure Cochlear promontory thickness. Results Among 48 included patients (96 ears), the mean (SD) age was 56 (18) years (range 25–94) and included 25 (52%) women. Of that 12 patients (25%) had osteopenia (n = 6) or osteoporosis (n = 6). The mean (SD) body mass index was 28 (5) kg/m2. The mean (SD) promontory thickness for the 96 temporal bones under study was 1.22 (0.24) mm (range 0.55–1.85). There was not a statistically significant association between age and promontory thickness (correlation coefficient .08; p = .44). Promontory thickness was significantly greater for men than women (mean 1.28 vs. 1.17 mm; p = .03) and increased with increasing body mass index (correlation coefficient .30; p = .004). Last, promontory thickness was significantly less for patients with osteopenia or osteoporosis compared with those without these conditions (mean 1.09 vs. 1.27 mm; p = .002). Conclusions Cochlear promontory thickness can vary by almost 1.5 mm across patients and is significantly associated with patient sex, body mass index, and comorbid osteopenia/osteoporosis. Subendosteal and transpromontory electrode placement techniques must account for this degree of variability. Level of Evidence IV

Abstract In practice, the capacitance from the electrochemical double layer formation on porous carbon‐based electrodes is still below preferred values, limiting their use in electrochemical capacitors. The current drive is to innovate ways that generate additional capacitance in the electrochemical double layer capacitive nature of carbon nanomaterials towards both a high specific energy density (Es) and power density (Ps). Herein we report the use of metal‐organic chemical vapor deposition (MOCVD) to coat multiwalled carbon nanotubes (MWCNTs) with anatase titanium dioxide (TiO2) to induce pseudocapacitive charge storage characteristics on a carbon‐based electrode. The study shows that MWCNTs were coated in bundles, and targeted TiO2 loadings were successfully attained, though the TiO2 agglomerates also increased with TiO2 wt.%. The 10 wt.% TiO2 TiO2‐MWCNT material displayed the best capacitive behavior with associated specific discharge capacitance (Cd), Es, and Ps values of 907 F kg−1, 55.56 Wh kg−1, and 2.78 W kg−1 at 0.1 A g−1, respectively, due to the synergistic effect of the two components of the composite. Additionally, the integral capacitance (Cs) of the 20 wt.% TiO2 material was enhanced more than 5000‐fold relative to that of the 5 wt.% TiO2 TiO2‐MWCNT composite at higher scan speeds of 100 and 200 mV s−1. Electrochemical measurements further demonstrated the possible positive tuning of capacitive characteristics (charge/discharge rates, Cd and Cs) with TiO2 wt.% control. The MOCVD synthesis method imparted the TiO2‐MWCNT composites with suitable traits that showed high potential in improving physicochemical processes favorable in electrical energy storage.

Abstract Objective Although 911 calls for acute shortness of breath are common, the role of emergency medical services (EMS) in acute asthma care is unclear. We sought to characterize the demographics, course, and outcomes of adult emergency department (ED) patients with asthma in the United States receiving initial EMS care. Methods We analyzed data from the 2016–2019 National Hospital Ambulatory Medical Care Survey (NHAMCS). We included patients aged ≥18 years with an ED visit diagnosis of asthma, stratifying the cases according to initial EMS care. Accounting for the survey design of NHAMCS, we generated nationalized estimates of the number of EMS and non‐EMS asthma visits. Using logistic regression, we determined the associations between initial EMS care and patient demographics (age, sex, race, and insurance type), ED course (initial vital signs, triage category, testing, medications), and outcomes (hospital admission, ED length of stay). Results Of 435 million adult ED visits during 2016–2019, there were ≈5.3 million related to asthma (1.3 million annually, 1.2%; 95% confidence interval [CI], 1.1%–1.4%). A total of 602,569 (150,642 annually, 11.3%; 95% CI, 8.6%–14.8%) ED patients with asthma received initial EMS care. Compared with non‐EMS asthma patients, EMS asthma patients were more likely to present with an “urgent” ED triage category (odds ratio [OR], 22.2; 95% CI, 6.6–74.9) and to undergo laboratory (OR, 2.78; 95% CI, 1.41–5.46) or imaging tests (OR, 2.42; 95% CI, 1.21–4.83). ED patients with asthma receiving initial EMS care were almost 3 times more likely to be admitted to the hospital (OR, 2.81; 95% CI, 1.27–6.25). There were no differences in demographics, ED use of β‐agonists or corticosteroids, or ED length of stay between EMS and non‐EMS asthma patients. Conclusions Approximately 1 in 10 adult ED patients with asthma receive initial care by EMS. EMS asthma patients present to the ED with higher acuity, undergo more diagnostic testing in the ED, and are more likely to be admitted. Although limited in information regarding the prehospital course, these findings highlight the more severe illness of asthma patients transported by EMS and underscore the importance of EMS in emergency asthma care.

Abstract Objectives/hypothesis To identify sociodemographic factors associated with the development of airway stenosis (AS) among intubated medical intensive care unit (MICU) patients. Study design Retrospective cohort study. Methods A retrospective review of adult MICU intubated patients from 2013 to 2019 at a single academic institution was performed. Univariate and multivariate analysis with logistic regression examined associations between the development of AS and subsite abnormalities such as posterior glottic stenosis (PGS), subglottic stenosis (SGS), tracheal stenosis (TS), vocal fold immobility (VFI), and posterior glottic granuloma (PGG) with age, body mass index (BMI), height, weight, race, ethnicity, sex, rurality, Appalachian status, length of admission, distance to hospital, and median household income. Results Of an overall sample of 6603 MICU patients, 449 intubated patients were included in the study, and 204 patients were found to have AS. AS was statistically associated with decreased driving distance to the hospital and increases in BMI. PGS was statistically associated with increases in age. TS was statistically associated with increases in admission duration and not having residence status in Appalachia. VFI was statistically associated with decreases in driving distance to the hospital and not having residence status in Appalachia. Additionally, black patients had a higher odds of developing VFI compared to Caucasian patients. Conclusion AS is associated with sociodemographic factors such as age, BMI, shorter distance to hospital, admission duration, and no Appalachian status. These data demonstrate the need to further investigate the impact of social determinants of health on airway pathology and outcomes. Level of evidence 4.

Abstract Sea level rise (SLR) and saltwater intrusion are driving inland shifts in coastal ecosystems. Here, we make high‐resolution (1 m) predictions of land conversion under future SLR scenarios in 81 watersheds surrounding Chesapeake Bay, United States, a hotspot for accelerated SLR and saltwater intrusion. We find that 1050–3748 km2 of marsh could be created by 2100, largely at the expense of forested wetlands. Predicted marsh migration exceeds total current tidal marsh area and is ~ 4× greater than historical observations. Anthropogenic land use in marsh migration areas is concentrated within a few watersheds and minimally impacts calculated metrics of marsh resilience. Despite regional marsh area maintenance, local ecosystem service replacement within vulnerable watersheds remains uncertain. However, our work suggests that topography rather than land use drives spatial variability in wetland vulnerability regionally, and that rural land conversion is needed to compensate for extensive areal losses on heavily developed coasts globally.

Abstract Objective To comprehensively review the recent published literature to characterize current trends of burnout and well‐being among otolaryngology trainees. Methods Study design: systematic review and meta‐analysis. A comprehensive literature review from 2000 to 2021 of studies related to otolaryngology resident burnout and well‐being, as well as the general topic of well‐being among surgical residents was completed. All included studies were summarized qualitatively. For the quantitative analysis, only articles reporting a Maslach burnout inventory (MBI), modified MBI or Mini‐Z‐ Burnout assessment were included. Results Twenty‐five articles were included in the qualitative summary and nine articles in the quantitative analysis. In the qualitative summary, trainees were reported to have increased levels of distress and emotional hardening compared to attending otolaryngologists. Total hours worked per week and female gender were associated with worsened well‐being. Residency program strategies to improve trainee well‐being include program‐sponsored wellness activities, dedicated wellness champions, and assistance with clerical burden. Implementation of protected nonclinical time has been shown to decrease burnout and increase well‐being among trainees. Moreover, formal trainee mentorship programs have also been shown to reduce trainee burnout and stress. In the quantitative analysis, rates of trainee burnout ranged from 29.7% to 86% with an overall trend towards reduced rates of burnout from 2006 to 2021. Utilizing a weighted average, the overall burnout among otolaryngology residents was 58.6%. Conclusions Rates of burnout remain high among otolaryngology trainees. Implementing formal mentorship programs and providing protected time during regular work hours appear to be effective tools to improve resident well‐being.

Abstract Tidal marsh survival in the face of sea level rise (SLR) and declining sediment supply often depends on the ability of marshes to build soil vertically. However, numerical models typically predict survival under rates of SLR that far exceed field‐based measurements of vertical accretion. Here, we combine novel measurements from seven U.S. Atlantic Coast marshes and data from 70 additional marshes from around the world to illustrate that—over continental scales—70% of variability in marsh accretion rates can be explained by suspended sediment concentratin (SSC) and spring tidal range (TR). Apparent discrepancies between models and measurements can be explained by differing responses in high marshes and low marshes, the latter of which accretes faster for a given SSC and TR. Together these results help bridge the gap between models and measurements, and reinforce the paradigm that sediment supply is the key determinant of wetland vulnerability at continental scales.

Abstract Objective Describe the presentation and management strategy for patients with symptomatic foramen of Huschke (FH). Patients Adults with persistent FH confirmed on imaging. Interventions Diagnosis and management of symptomatic persistent FH. Main outcome measure Resolution of otologic symptoms. Results A total of four patients with symptomatic, radiographically‐confirmed persistent FH were included. The majority of patients endorsed otalgia (n = 4) and otorrhea (n = 3), and only one patient was noted to have a conductive hearing loss. All patients were noted to have dynamic movement of an external auditory canal mass with mandible manipulation on examination, and all patients had an identifiable fistula on imaging. Patients underwent surgical intervention, including both preauricular (n = 2) and transcanal (n = 2) approaches, and all endorsed symptomatic resolution after convalescence. Conclusions Persistent FH remains an uncommon and potentially underrecognized cause of otologic symptoms. Diagnosis requires a high index of suspicion, and one must rely on both key examination findings and imaging to confirm this diagnosis. In appropriately selected patients, surgical intervention can provide durable symptomatic resolution. Level of evidence IV

Abstract In the phase III RESTORE‐IMI 2 study (ClinicalTrials.gov: NCT02493764), the combination antibacterial agent imipenem/cilastatin/relebactam (IMI/REL) demonstrated noninferiority to piperacillin/tazobactam for the end points of all‐cause mortality at day 28 and favorable clinical response at the early follow‐up visit in adult participants with gram‐negative hospital‐acquired bacterial pneumonia/ventilator‐associated bacterial pneumonia (HABP/VABP). Existing population pharmacokinetic models for imipenem (IPM) and REL were updated using data from patients with HABP/VABP from RESTORE‐IMI 2. Creatinine clearance (CrCl), body weight, infection type, and ventilation status were significant covariates in the updated model. The following simulations were performed to calculate the pharmacokinetic/pharmacodynamic joint probability of target attainment among patients with HABP/VABP and varying degrees of renal function: augmented renal clearance (CrCl ≥150 ml/min), normal renal function (CrCl ≥90 to

ABSTRACT Perennial grass energy crop production is necessary for the successful and sustainable expansion of bioenergy in North America. Numerous environmental advantages are associated with perennial grass cropping systems, including their potential to promote soil carbon accrual. Despite growing research interest in the abiotic and biotic factors driving soil carbon cycling within perennial grass cropping systems, soil fauna remain a critical yet largely unexplored component of these ecosystems. By regulating microbial activity and organic matter decomposition dynamics, soil fauna influence soil carbon stability with potentially significant implications for soil carbon accrual. We begin by reviewing the diverse, predominantly indirect effects of soil fauna on soil carbon dynamics in the context of perennial grass cropping systems. Since the impacts of perennial grass energy crop production on soil fauna will mediate their potential contributions to soil carbon accrual, we then discuss how perennial grass energy crop traits, diversity, and management influence soil fauna community structure and activity. We assert that continued research into the interactions of soil fauna, microbes, and organic matter will be important for advancing our understanding of soil carbon dynamics in perennial grass cropping systems. Furthermore, explicit consideration of soil faunal effects on soil carbon can improve our ability to predict changes in soil carbon following perennial grass cropping system establishment. We conclude by addressing the major knowledge gaps that should be prioritized to better understand and model the complex connections between perennial grass bioenergy systems, soil fauna, and carbon accrual.

Abstract Background In humans, washing stored blood products before transfusion reduces storage lesions and incidence of transfusion reactions, but the effectiveness of washing canine blood is unknown. Objectives The objective was to determine if manually washing units of stored blood would reduce storage lesions without adversely affecting erythrocytes. We hypothesized that washing stored units would reduce concentrations of storage lesions and cause minimal erythrocyte damage. Animals Eight healthy research dogs. Methods Repeated measure cohort study. Units of whole blood were stored for 28 days and washed 3 times with 0.9% NaCl. Blood samples were collected before and after storage, after each wash, and after being held at a simulated transfusion temperature. Variables measured included CBC variables, blood gas analysis, erythrocyte morphology, mean corpuscular fragility (MCF), and eicosanoid concentrations. A Friedman's test was used to evaluate changes in variables (P < .05 was considered significant). Results After the first wash, compared to values after storage, there was a significant decrease in potassium (4.3 mmol/L [4.0‐4.7] to 1.2 mmol/L [1‐1.6]; P < .0001, median [range]), lactate (1.45 mmol/L [1.07‐1.79] to 0.69 mmol/L [0.39‐0.93]; P = .002), and partial pressure carbon dioxide (102 mm Hg [80.2‐119.2] to 33.7 mm Hg [24.5‐44.5]; P < .0001), and increase in MCV (69.3 fL [65.7‐72.3] to 74 fL [69.6‐79.5]; P = .0003), and MCF (0.444 fL [0.279‐0.527] to 0.491 fL [0.43‐0.616]; P = .0006). Conclusions and Clinical Importance A single wash of stored whole blood significantly reduces most extracellular storage lesions, and additional washing might cause hemolysis.

Abstract Synthesis research in ecology and environmental science improves understanding, advances theory, identifies research priorities, and supports management strategies by linking data, ideas, and tools. Accelerating environmental challenges increases the need to focus synthesis science on the most pressing questions. To leverage input from the broader research community, we convened a virtual workshop with participants from many countries and disciplines to examine how and where synthesis can address key questions and themes in ecology and environmental science in the coming decade. Seven priority research topics emerged: (1) diversity, equity, inclusion, and justice (DEIJ), (2) human and natural systems, (3) actionable and use‐inspired science, (4) scale, (5) generality, (6) complexity and resilience, and (7) predictability. Additionally, two issues regarding the general practice of synthesis emerged: the need for increased participant diversity and inclusive research practices; and increased and improved data flow, access, and skill‐building. These topics and practices provide a strategic vision for future synthesis in ecology and environmental science.

Abstract Objective Otolaryngology residency is highly competitive, and applicant academic metrics are scrutinized. The predictive value of preresidency academic metrics on applicants’ future research productivity and career aspirations remains largely undefined. Study Design Retrospective cohort study Setting Academic otolaryngology department, 2014 to 2015. Methods Applicant demographics, publication history, and United States Medical Licensing Examination (USMLE) scores were downloaded from Electronic Residency Application Service archives. Publications during residency were tallied from all PubMed articles indexed between July 1, 2015 and June 30, 2020. Postresidency career paths were examined by 2 investigators (D.J.C. and L.X.Y.) using Google searches with an emphasis on program websites, Doximity, and LinkedIn profiles. Associations with publication potential and postresidency positions were evaluated with Spearman rank correlation coefficients and Kruskal‐Wallis, Wilcoxon rank sum, and χ2 tests. Results Of 321 applicants, 226 (70%) matched, and 205 (64%) completed residency by June 2020. Matched residents published a median of 4 (range: 0‐41) manuscripts during residency. USMLE scores, Alpha Omega Alpha status, and the number of preresidency publications did not significantly correlate with publication potential during residency. The number of research experiences had a significant positive correlation with publications during residency (p

Abstract Bespoke (custom‐built) Raspberry Pi cameras are increasingly popular research tools in the fields of behavioral ecology and conservation, because of their comparative flexibility in programmable settings, ability to be paired with other sensors, and because they are typically cheaper than commercially built models. Here, we describe a novel, Raspberry Pi‐based camera system that is fully portable and yet weatherproof—especially to humidity and salt spray. The camera was paired with a passive infrared sensor, to create a movement‐triggered camera capable of recording videos over a 24‐hr period. We describe an example deployment involving “retro‐fitting” these cameras into artificial nest boxes on Praia Islet, Azores archipelago, Portugal, to monitor the behaviors and interspecific interactions of two sympatric species of storm‐petrel (Monteiro's storm‐petrel Hydrobates monteiroi and Madeiran storm‐petrel Hydrobates castro) during their respective breeding seasons. Of the 138 deployments, 70% of all deployments were deemed to be “Successful” (Successful was defined as continuous footage being recorded for more than one hour without an interruption), which equated to 87% of the individual 30‐s videos. The bespoke cameras proved to be easily portable between 54 different nests and reasonably weatherproof (~14% of deployments classed as “Partial” or “Failure” deployments were specifically due to the weather/humidity), and we make further trouble‐shooting suggestions to mitigate additional weather‐related failures. Here, we have shown that this system is fully portable and capable of coping with salt spray and humidity, and consequently, the camera‐build methods and scripts could be applied easily to many different species that also utilize cavities, burrows, and artificial nests, and can potentially be adapted for other wildlife monitoring situations to provide novel insights into species‐specific daily cycles of behaviors and interspecies interactions.

Abstract The importance of thermal refuges in a rapidly warming world is particularly evident for migratory species, where individuals encounter a wide range of conditions throughout their lives. In this study, we used a spatially explicit, individual‐based simulation model to evaluate the buffering potential of cold‐water thermal refuges for anadromous salmon and trout (Oncorhynchus spp.) migrating upstream through a warm river corridor that can expose individuals to physiologically stressful temperatures. We considered upstream migration in relation to migratory phenotypes that were defined in terms of migration timing, spawn timing, swim speed, and use of cold‐water thermal refuges. Individuals with different migratory phenotypes migrated upstream through riverine corridors with variable availability of cold‐water thermal refuges and mainstem temperatures. Use of cold‐water refuges (CWRs) decreased accumulated sublethal exposures to physiologically stressful temperatures when measured in degree‐days above 20, 21, and 22°C. The availability of CWRs was an order of magnitude more effective in lowering accumulated sublethal exposures under current and future mainstem temperatures for summer steelhead than fall Chinook Salmon. We considered two emergent model outcomes, survival and percent of available energy used, in relation to thermal heterogeneity and migratory phenotype. Mean percent energy loss attributed to future warmer mainstem temperatures was at least two times larger than the difference in energy used in simulations without CWRs for steelhead and salmon. We also found that loss of CWRs reduced the diversity of energy‐conserving migratory phenotypes when we examined the variability in entry timing and travel time outside of CWRs in relation to energy loss. Energy‐conserving phenotypic space contracted by 7%–23% when CWRs were unavailable under the current thermal regime. Our simulations suggest that, while CWRs do not entirely mitigate for stressful thermal exposures in mainstem rivers, these features are important for maintaining a diversity of migration phenotypes. Our study suggests that the maintenance of diverse portfolios of migratory phenotypes and cool‐ and cold‐water refuges might be added to the suite of policies and management actions presently being deployed to improve the likelihood of Pacific salmonid persistence into a future characterized by climate change.

Abstract Predator–prey systems face intensifying pressure from human exploitation and a warming climate with implications for where and how natural resource management can successfully intervene. We hypothesized young salmon migrating to the Pacific Ocean face a seasonally intensifying predator gauntlet when warming water temperature intensifies a multiple predator effect (MPE) from Striped Bass Morone saxatilis and Largemouth Bass Micropterus salmoides. We evaluated this hypothesis using data synthesis and simulation modeling. Contemporary studies based on acoustically tagged fish reaffirmed older observations that Chinook Salmon smolts must transit the Delta before water temperature reaches 20°C or mortality will be nearly 100%. Striped Bass attack rates on tethered smolts were insensitive to distance from shore and water temperature, whereas Largemouth Bass attack rates were highest near shorelines in warm water, supporting the temporal aspect of the hypothesis. Whether the combined effects of the two predators produce an MPE remains unconfirmed due to limitations on quantifying salmon behavior. We used multiple simulation models to try to reconstruct the empirical relationship between smolt survival and water temperature. Simulations reinforced attack rate results, but could not recreate the temperature dependence in smolt survival except at higher than observed temperatures. We propose three hypotheses for why and recommend discerning among them should be a focus of research. We found significant linear relationships between monthly mean inflow to the Delta from each of its two largest tributaries and monthly mean water temperatures along associated salmon migration routes, but these relationships can be nonlinear, with most of the correlation occurring at low inflows when water temperature is largely controlled by air temperature and day length. As the global climate warms, changed circumstances in predator–prey relationships may present important challenges when managing species vulnerable to extinction in addition to presently more abundant species.

The epigenomic regulation of transcriptional programs in metastatic prostate cancer is poorly understood. We studied the epigenomic landscape of prostate cancer drivers using transcriptional profiling and ChIP‐seq in four clonal metastatic tumors derived from a single prostate cancer patient. Our epigenomic analyses focused on androgen receptor (AR), which is a key oncogenic driver in prostate cancer, the AR pioneer factor FOXA1, chromatin insulator CCCTC‐Binding Factor, as well as for modified histones H3K27ac and H3K27me3. The vast majority of AR binding sites were shared among healthy prostate, primary prostate cancer, and metastatic tumor samples, signifying core AR‐driven transcriptional regulation within the prostate cell lineage. Genes associated with core AR‐binding events were significantly enriched for essential genes in prostate cancer cell proliferation. Remarkably, the metastasis‐specific active AR binding sites showed no differential transcriptional output, indicating a robust transcriptional program across metastatic samples. Combined, our data reveal a core transcriptional program in clonal metastatic prostate cancer, despite epigenomic differences in the AR cistrome.

Abstract Uprifosbuvir is a uridine nucleoside monophosphate prodrug inhibitor of the hepatitis C virus NS5B RNA polymerase. To quantitatively elucidate key metabolic pathways, assess the link between unmeasurable effect site concentrations and viral load reduction, and evaluate the influence of intrinsic and extrinsic factors on pharmacokinetics and pharmacodynamics, a model‐informed drug development (MIDD) framework was initiated at an early stage. Originally scoped as a modeling effort focused on minimal physiologically based pharmacokinetic and covariate analyses, this project turned into a collaborative effort focused on gaining a deeper understanding of the data from drug metabolism, biopharmaceutics, pharmacometrics, and clinical pharmacology perspectives. This article presents an example of the practical execution of a MIDD‐based, cooperative multidisciplinary modeling approach, creating a model that grows along with the team's integrated knowledge. Insights gained from this process could be used in forming optimal collaborations between disciplines in drug development for other investigative compounds.

Abstract Biodiversity is in crisis, and insects are no exception. To understand insect population and community trends globally, it is necessary to identify and synthesize diverse datasets representing different taxa, regions, and habitats. The relevant literature is, however, vast and challenging to aggregate. The Entomological Global Evidence Map (EntoGEM) project is a systematic effort to search for and catalogue studies with long‐term data that can be used to understand changes in insect abundance and diversity. Here, we present the overall EntoGEM framework and results of the first completed subproject of the systematic map, which compiled sources of information about changes in dragonfly and damselfly (Odonata) occurrence, abundance, biomass, distribution, and diversity. We identified 45 multi‐year odonate datasets, including 10 studies with data that span more than 10 years. If data from each study could be gathered or extracted, these studies could contribute to analyses of long‐term population trends of this important group of indicator insects. The methods developed to support the EntoGEM project, and its framework for synthesizing a vast literature, have the potential to be applied not only to other broad topics in ecology and conservation, but also to other areas of research where data are widely distributed.

Abstract Symbioses between Geosmithia fungi and wood‐boring and bark beetles seldom result in disease induction within the plant host. Yet, exceptions exist such as Geosmithia morbida, the causal agent of Thousand Cankers Disease (TCD) of walnuts and wingnuts, and Geosmithia sp. 41, the causal agent of Foamy Bark Canker disease of oaks. Isolates of G. obscura were recovered from black walnut trees in eastern Tennessee and at least one isolate induced cankers following artificial inoculation. Due to the putative pathogenicity and lack of recovery of G. obscura from natural lesions, a molecular diagnostic screening tool was developed using microsatellite markers mined from the G. obscura genome. A total of 3256 candidate microsatellite markers were identified (2236, 789, 137 di‐, tri‐, and tetranucleotide motifs, respectively), with 2011, 703, 101 di‐, tri‐, and tetranucleotide motifs, respectively, containing markers with primers. From these, 75 microsatellite markers were randomly selected, screened, and optimized, resulting in 28 polymorphic markers that yielded single, consistently recovered bands, which were used in downstream analyses. Five of these microsatellite markers were found to be specific to G. obscura and did not cross‐amplify into other, closely related species. Although the remaining tested markers could be useful, they cross‐amplified within different Geosmithia species, making them not reliable for G. obscura detection. Five novel microsatellite markers (GOBS9, GOBS10, GOBS41, GOBS43, and GOBS50) were developed based on the G. obscura genome. These species‐specific microsatellite markers are available as a tool for use in molecular diagnostics and can assist future surveillance studies.

Abstract Stocking of fish is an important tool for maintaining fisheries but can also significantly alter population genetic structure and erode the portfolio of within‐species diversity that is important for promoting resilience and adaptability. Walleye (Sander vitreus) are a highly valued sportfish in the midwestern United States, a region characterized by postglacial recolonization from multiple lineages and an extensive history of stocking. We leveraged genomic data and recently developed analytical approaches to explore the population structure of walleye from two midwestern states, Minnesota and Wisconsin. We genotyped 954 walleye from 23 populations at ~20,000 loci using genotyping by sequencing and tested for patterns of population structure with single‐SNP and microhaplotype data. Populations from Minnesota and Wisconsin were highly differentiated from each other, with additional substructure found in each state. Population structure did not consistently adhere to drainage boundaries, as cases of high intra‐drainage and low inter‐drainage differentiation were observed. Low genetic structure was observed between populations from the upper Wisconsin and upper Chippewa river watersheds, which are found as few as 50 km apart and were likely homogenized through historical stocking. Nevertheless, we were able to differentiate these populations using microhaplotype‐based co‐ancestry analysis, providing increased resolution over previous microsatellite studies and our other single SNP‐based analyses. Although our results illustrate that walleye population structure has been influenced by past stocking practices, native ancestry still exists in most populations and walleye populations may be able to purge non‐native alleles and haplotypes in the absence of stocking. Our study is one of the first to use genomic tools to investigate the influence of stocking on population structure in a nonsalmonid fish and outlines a workflow leveraging recently developed analytical methods to improve resolution of complex population structure that will be highly applicable in many species and systems.

Abstract Global climate models (GCMs) are essential for investigating climate change, but their coarse scale limits their efficacy for climate adaptation planning at the regional scales where climate impacts manifest. Dynamical downscaling of GCM outputs better resolves regional climate and thus provides improved guidance for climate policy at regional scales. Being expensive to run, downscaling uses a subset of GCMs, necessitating careful GCM selection. This evaluation identifies a suitable subset of CMIP6 GCMs for downscaling over Australia by assessing individual GCMs against three criteria: (a) performance simulating daily climate variable distributions, climate means, extremes, and modes; (b) model independence; and (c) climate change signal diversity. Over Australia, GCMs are generally biased cold (warm) for maximum (minimum) temperature, with larger biases for minimum temperature. GCMs are generally wet biased, especially over the monsoonal north, but dry biased over eastern regions. Most GCMs show larger biases for temperature and precipitation over geographically complex, heavily populated eastern regions, relative to other regions. Evaluations identify a distinct group of 11 GCMs that perform consistently poorly across climate variables, statistics, and timescales with widespread, statistically significant biases, versus 13 GCMs that show consistent adequate‐to‐good performance with substantially reduced errors. Assessment of model independence highlights the lack of independence between several high‐performing GCMs, particularly from allied modeling groups, demonstrating the importance of careful ensemble selection when making selective samples of climate space. Once GCM climate signal diversity is considered, 6–8 mid‐to‐high‐performing, independent GCMs occupy the full range of the future climate space and, thus, are suitable for dynamical downscaling over CORDEX‐Australasia.

Abstract Study objective Triage quickly identifies critically ill patients, facilitating timely interventions. Many emergency departments (EDs) use emergency severity index (ESI) or abnormal vital sign triggers to guide triage. However, both use fixed thresholds, and false activations are costly. Prior approaches using machinelearning have relied on information that is often unavailable during the triage process. We examined whether deep‐learning approaches could identify critically ill patients only using data immediately available at triage. Methods We conducted a retrospective, cross‐sectional study at an urban tertiary care center, from January 1, 2012–January 1, 2020. De‐identified triage information included structured (age, sex, initial vital signs) and textual (chief complaint) data, with critical illness (mortality or ICU admission within 24 hours) as the outcome. Four progressively complex deep‐learning models were trained and applied to triage information from all patients. We compared the accuracy of the models against ESI as the standard diagnostic test, using area under the receiver‐operator curve (AUC). Results A total of 445,925 patients were included, with 60,901 (13.7%) critically ill. Vital sign thresholds identified critically ill patients with AUC 0.521 (95% confidence interval [CI] = 0.519–0.522), and ESI

Abstract Objective The current standard of care for initial neuroimaging in injured pediatric patients suspected of having traumatic brain injury is computed tomography (CT) that carries risks associated with radiation exposure. The primary objective of this trial was to evaluate the ability of a QuickBrain MRI (qbMRI) protocol to detect clinically important traumatic brain injuries in the emergency department (ED). The secondary objective of this trial was to compare qbMRI to CT in identifying radiographic traumatic brain injury. Methods This was a prospective study of trauma patients less than 15 years of age with suspected traumatic brain injury at a level 1 pediatric trauma center in Portland, Oregon between August 2017 and March 2019. All patients in whom a head CT was deemed clinically necessary were approached for enrollment to also obtain a qbMRI in the acute setting. Clinically important traumatic brain injury was defined as the need for neurological surgery procedure, intubation, pediatric intensive care unit stay greater than 24 hours, a total hospital length of stay greater than 48 hours, or death. Results A total of 73 patients underwent both CT and qbMRI. The median age was 4 years (interquartile range [IQR] = 1–10 years). Twenty‐two patients (30%) of patients had a clinically important traumatic brain injury, and of those, there were 2 deaths (9.1%). QbMRI acquisition time had a median of 4 minutes and 52 seconds (IQR = 3 minutes 49 seconds–5 minutes 47 seconds). QbMRI had sensitivity for detecting clinically important traumatic brain injury of 95% (95% confidence interval [CI] = 77%–99%). For any radiographic injury, qbMRI had a sensitivity of 89% (95% CI = 78%–94%). Conclusion Our results suggest that qbMRI has good sensitivity to detect clinically important traumatic brain injuries. Further multi‐institutional, prospective trials are warranted to either support or refute these findings.

Abstract Uncertainty in risks posed by emerging stressors such as synthetic hormones impedes conservation efforts for threatened vertebrate populations. Synthetic hormones often induce sex‐biased perturbations in exposed animals by disrupting gonad development and early life‐history stage transitions, potentially diminishing per capita reproductive output of depleted populations and, in turn, being manifest as Allee effects. We use a spatially explicit biophysical model to evaluate how sex‐biased perturbation in life‐history traits of individuals (maternal investment in egg production and male‐skewed sex allocation in offspring) modulates density feedback control of year‐class strength and recovery trajectories of a long‐lived, migratory fish—shovelnose sturgeon (Scaphirhynchus platorynchus)—under spatially and temporally dynamic synthetic androgen exposure and habitat conditions. Simulations show that reduced efficiency of maternal investment in gonad development prolonged maturation time, increased the probability of skipped spawning, and, in turn, shrunk spawner abundance, weakening year‐class strength. However, positive density feedback disappeared (no Allee effect) once the exposure ceased. By contrast, responses to the demographic perturbation manifested as strong positive density feedback; an abrupt shift in year‐class strength and spawner abundance followed after more than two decades owing to persistent negative population growth (a strong Allee effect), reaching an alternative state without any sign of recovery. When combined with the energetic perturbation, positive density feedback of the demographic perturbation was dampened as extended maturation time reduced the frequency of producing male‐biased offspring, allowing the population to maintain positive growth rate (a weak Allee effect) and gradually recover. The emergent patterns in long‐term population projections illustrate that sex‐biased perturbation in life‐history traits can interactively regulate the strength of density feedback in depleted populations such as Scaphirhynchus sturgeon to further diminish reproductive capacity and abundance, posing increasingly greater conservation challenges in chemically altered riverscapes.

Abstract Modern metabolomic approaches that generate more comprehensive phytochemical profiles than were previously available are providing new opportunities for understanding plant‐animal interactions. Specifically, we can characterize the phytochemical landscape by asking how a larger number of individual compounds affect herbivores and how compounds covary among plants. Here we use the recent colonization of alfalfa (Medicago sativa) by the Melissa blue butterfly (Lycaeides melissa) to investigate the effects of indivdiual compounds and suites of covarying phytochemicals on caterpillar performance. We find that survival, development time, and adult weight are all associated with variation in nutrition and toxicity, including biomolecules associated with plant cell function as well as putative anti‐herbivore action. The plant‐insect interface is complex, with clusters of covarying compounds in many cases encompassing divergent effects on different aspects of caterpillar performance. Individual compounds with the strongest associations are largely specialized metabolites, including alkaloids, phenolic glycosides, and saponins. The saponins are represented in our data by more than 25 individual compounds with beneficial and detrimental effects on L. melissa caterpillars, which highlights the value of metabolomic data as opposed to approaches that rely on total concentrations within broad defensive classes.