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Abstract It is difficult to model changes in the likelihood of tropical cyclones under climate change to date. We do this, for the first time, by a applying a stochastic tropical cyclone event set generated by the Imperial College Storm Model to attribute the contribution of climate change to the case of Typhoon Haiyan in 2013. Compared to a pre‐industrial baseline, we estimate that a typhoon with a landfall maximum wind speed like Haiyan was larger by +3.5 m/s. This is in good agreement with previous full physics numerical model estimates. A Haiyan type of event has a current return period of 850 years, and the fractional attributable risk due to climate change is 98%. Without climate change, this event was very unlikely. The type of information available from the IRIS model could inform subsidizing of catastrophe bond yield in the context of the loss and damage fund.

Abstract Melatonin is a multifunctional biomolecule with demonstrated stimulatory, inhibitory, and antioxidant effects, including both receptor‐mediated and receptor‐independent mechanisms of action. One of its more perplexing effects is the disruption of regeneration in planaria. Head regeneration in planaria is a remarkable phenomenon in which stem cells (neoblasts) migrate to the wound site, proliferate, then differentiate into all functional tissue types within days of injury. We investigated how both the timing and duration of melatonin exposure affect head regeneration in the planaria Phagocata gracilis (Haldeman). Our results demonstrate that P. gracilis is capable of recovery from the melatonin‐induced delay of regeneration and reveal the time required to recover to control levels. Further, we found evidence of regenerative stage‐specific responses to discontinuous melatonin exposure, including non‐inhibitory effects. Further exploration of melatonin's effects on regeneration can be targeted to specific regenerative processes, and the possibility of multiple mechanisms of action should be recognized.

Abstract A major intent of scientific research is the replication of the behaviour observed in natural spaces. In robotics, these can be through biomimetic movements in devices and inspiration from diverse actions in nature, also known as bioinspired features. An interesting pathway enabling both features is the fabrication of soft actuators. Specifically, 3D‐printing has been explored as a potential approach for the development of biomimetic and bioinspired soft actuators. The extent of this method is highlighted through the large array of applications and techniques used to create these devices, as applications from the movement of fern trees to contraction in organs are explored. In this review, different 3D‐printing fabrication methods, materials, and types of soft actuators, and their respective applications are discussed in depth. Finally, the extent of their use for present operations and future technological advances are discussed.

Objective RheumMadness is an online learning collaborative that seeks to actively engage the rheumatology community. The objective of this manuscript is to analyze the educational experience of RheumMadness over two years. Methods Direct measures of participant engagement were obtained using web‐based analytics. An electronic survey was created after the tournament to capture self‐reported engagement and educational experience using the Community of Inquiry framework. Data were analyzed according to the following objectives: (1) compare demographics, engagement, and educational experience of participants between 2021 and 2022; (2) describe the educational experience of those who created scouting reports; (3) explore the impact of RheumMadness on early learners (medical students and residents). Results Compared with 2021, the 2022 tournament had more participants who submitted a bracket, more early learners, and more scouting report creators. Self‐reported engagement and educational experience was high in both years of the tournament among all participants. Over 85% of scouting report creators reported that making a report was a fun and valuable learning experience. Early learners reported significantly higher levels of knowledge integration, sense of belonging in the rheumatology community, social connection, and overall learning experience compared with more advanced participants. Eighty‐five percent of early learners reported that RheumMadness increased their interest in rheumatology. Conclusion RheumMadness expanded from 2021 to 2022, engaging more participants in collaborative learning. Our results demonstrate that RheumMadness is particularly impactful among medical students and residents by helping them explore rheumatology topics and connect with the rheumatology community.

Abstract Cities are concentrators of complex, multi‐sectoral interactions. As keystones in the interconnected human‐Earth system, cities have an outsized impact on the Earth system. We describe a multi‐lens framework for organizing our understanding of the complexity of urban systems and scientific research on urban systems, which may be useful for natural system scientists exploring the ways their work can be made more actionable. We then describe four critical dimensions along which improvements are needed to advance the urban research that addresses urgent climate challenges: (a) solutions‐oriented research, (b) equity‐centered assessments which rely on fine‐scale human and ecological data, (c) co‐production of knowledge, and (d) better integration of human and natural systems occurring through theory, observation, and modeling.

Abstract The gradual accumulation of phosphorus from historical fertilization can contribute to the eutrophication of surface waters by increasing the potential for subsurface leaching losses. Grazing lands areas are a priority for concern, and phytoremediation efforts in grazing lands have prioritized grasses that may be used as forage for cattle. This study investigated the influence of three different forage species—Paspalum notatum, Hemarthria altissima, and Cynodon nlemfuensis—on the loss of phosphorus in leachate from surface soils. The experiment used a nested pot mesocosm design that allowed us to monitor leachate volume and concentration biweekly over the course of 3 months. Pots containing P. notatum plants leached significantly more phosphorus than pots containing C. nlemfuensis or empty pots with no plants growing in them, despite losing an equivalent amount of water. H. altissima lost equivalent amounts of phosphorus in leachate water, but each H. altissima plant removed approximately 33.6 mg of phosphorus, approximately 2.5× that removed by P. notatum (13.4 mg). C. nlemfuensis had lower average leachate phosphorus concentrations at each biweekly sampling than either plant species (C. nlemfuensis‐P. notatum, padj = 0.001; C. nlemfuensis‐H. altissima, padj = 0.02), averaging only 0.110 ppm in leachate relative to 0.175 ppm and 0.200 ppm in pots beneath H. altissima and P. notatum, respectively. This, combined with C. nlemfuensis' slightly higher‐than‐average aboveground P content and overall aboveground biomass expression suggest it is the best possible phytoremediation candidate. As even minor leachate P loads can be critically threatening to neighboring oligotrophic water bodies, if the conservation of downstream environments is the priority, the short‐term threat of increased leachate must be considered. Further research is needed to explore the underlying mechanisms and field‐scale implications of these findings.

Abstract Introduction Metastatic castration‐resistant prostate cancer (mCRPC) is a heterogeneous disease with prognoses varying from months to years at time of castration‐resistant diagnosis. Optimal first‐line therapy for those with different prognoses is unknown. Methods We conducted a retrospective cohort study of men in a national healthcare delivery system receiving first‐line therapy for mCRPC (abiraterone, enzalutamide, docetaxel, or ketoconazole) from 2010 to 2017, with follow‐up through 2019. Using commonly drawn prognostic labs at start of mCRPC therapy (hemoglobin, albumin, and alkaline phosphatase), we categorized men into favorable, intermediate, or poor prognostic groups depending on whether they had none, one to two, or all three laboratory values worse than designated laboratory cutoffs. We used Kaplan–Meier methods to examine prostate specific antigen (PSA) progression‐free and overall survival (OS) according to prognostic group and first‐line therapy, and multivariable cox regression to determine variables associated with survival outcomes. Results Among 4135 patients, median PSA progression‐free survival (PFS) was 6.9 months (95% confidence interval [CI] 6.6–7.3), and median OS 18.8 months (95% CI 18.0–19.6), ranging from 5.7 months (95% CI 4.8–7.0) in the poor prognosis group to 31.3 months (95% CI 29.7–32.9) in the favorable group. OS was similar regardless of initial treatment received for favorable and intermediate groups, but worse for those in the poor prognostic group who received ketoconazole (adjusted hazard ratio 2.07, 95% CI 1.2–3.6). PSA PFS was worse for those who received ketoconazole compared to abiraterone across all prognostic groups (favorable HR 1.76, 95% CI 1.34–2.31; intermediate HR 1.78, 95% CI 1.41–2.25; poor HR 8.01, 95% CI 2.93–21.9). Conclusion Commonly drawn labs at mCRPC treatment start may aid in predicting survival and response to therapies, potentially informing discussions with care teams. First‐line treatment selection impacts disease progression for all men with mCRPC regardless of prognostic group, but impacted OS only for men with poor prognosis at treatment start.

Abstract Background Abiraterone and enzalutamide are castration‐resistant prostate cancer (CRPC) therapies with potentially distinct associations with mental health symptoms given their differing antiandrogen targets. Methods We used national Veterans Health Administration data to identify patients with CRPC who received first‐line abiraterone or enzalutamide from 2010 to 2017. Using Poisson regression, we compared outpatient mental health encounters per 100 patient‐months on drug between the abiraterone and enzalutamide cohorts adjusting for patient factors (e.g., age). We compared mental health encounters in the year before versus after starting therapy using the McNemar test. Results We identified 2902 CRPC patients who received abiraterone (n = 1992) or enzalutamide (n = 910). We found no difference in outpatient mental health encounters between the two groups (adjusted incident rate ratio [aIRR] 1.04, 95% confidence interval [CI] 0.95–1.15). However, men with preexisting mental health diagnoses received 81.3% of the outpatient mental health encounters and had higher rates of these encounters with enzalutamide (aIRR 1.21, 95% CI 1.09–1.34). Among patients with ≥1 year of enrollment before and after starting abiraterone (n = 1139) or enzalutamide (n = 446), there was no difference in mental health care utilization before versus after starting treatment (17.0% of patients vs. 17.6%, p = 0.60, abiraterone; 16.4% vs. 18.4%, p = 0.26, enzalutamide). Conclusion We found no overall differences in mental health care utilization between CRPC patients who received first‐line abiraterone versus enzalutamide. However, men with preexisting mental health diagnoses received the majority of mental health care and had more mental health visits with enzalutamide.

Abstract Introduction Research driven by real‐world clinical data is increasingly vital to enabling learning health systems, but integrating such data from across disparate health systems is challenging. As part of the NCATS National COVID Cohort Collaborative (N3C), the N3C Data Enclave was established as a centralized repository of deidentified and harmonized COVID‐19 patient data from institutions across the US. However, making this data most useful for research requires linking it with information such as mortality data, images, and viral variants. The objective of this project was to establish privacy‐preserving record linkage (PPRL) methods to ensure that patient‐level EHR data remains secure and private when governance‐approved linkages with other datasets occur. Methods Separate agreements and approval processes govern N3C data contribution and data access. The Linkage Honest Broker (LHB), an independent neutral party (the Regenstrief Institute), ensures data linkages are robust and secure by adding an extra layer of separation between protected health information and clinical data. The LHB's PPRL methods (including algorithms, processes, and governance) match patient records using “deidentified tokens,” which are hashed combinations of identifier fields that define a match across data repositories without using patients' clear‐text identifiers. Results These methods enable three linkage functions: Deduplication, Linking Multiple Datasets, and Cohort Discovery. To date, two external repositories have been cross‐linked. As of March 1, 2023, 43 sites have signed the LHB Agreement; 35 sites have sent tokens generated for 9 528 998 patients. In this initial cohort, the LHB identified 135 037 matches and 68 596 duplicates. Conclusion This large‐scale linkage study using deidentified datasets of varying characteristics established secure methods for protecting the privacy of N3C patient data when linked for research purposes. This technology has potential for use with registries for other diseases and conditions.

Abstract Objective Epilepsy is associated with an increased risk of cardiovascular disease and mortality. Whether cardiac structure and function are altered in epilepsy remains unclear. To address this, we conducted a systematic review and meta‐analysis of studies evaluating cardiac structure and function in patients with epilepsy. Methods We searched the electronic databases MEDLINE, PubMed, COCHRANE, and Web of Science from inception to 31 December 2021. Primary outcomes of interest included left ventricular ejection fraction (LVEF) for studies reporting echocardiogram findings and cardiac weight and fibrosis for postmortem investigations. Study quality was assessed using the National Heart, Lung, and Blood Institute (NHLBI) assessment tools. Results Among the 10 case‐control studies with epilepsy patients (n = 515) and healthy controls (n = 445), LVEF was significantly decreased in epilepsy group compared with controls (MD: −1.80; 95% confidence interval [CI]: −3.56 to −0.04; P = 0.045), whereas A‐wave velocity (MD: 4.73; 95% CI: 1.87‐7.60; P = 0.001), E/e' ratio (MD: 0.39; 95% CI: 0.06‐0.71; P = 0.019), and isovolumic relaxation time (MD: 10.18; 95% CI: 2.05‐18.32; P = 0.014) were increased in epilepsy, compared with controls. A pooled analysis was performed in sudden unexpected death in epilepsy (SUDEP) cases with autopsy data (n = 714). Among SUDEP cases, the prevalence of cardiac hypertrophy was 16% (95% CI: 9%–23%); cardiac fibrosis was 20% (95% CI: 15%–26%). We found no marked differences in cardiac hypertrophy, heart weight, or cardiac fibrosis between SUDEP cases and epilepsy controls. Significance Our findings suggest that epilepsy is associated with altered diastolic and systolic echocardiogram parameters compared with healthy controls. Notably, SUDEP does not appear to be associated with a higher incidence of structural cardiac abnormalities, compared with non‐SUDEP epilepsy controls. Longitudinal studies are needed to understand the prognostic significance of such changes. Echocardiography may be a useful noninvasive diagnostic test in epilepsy population.

Abstract Background Over the past decade, abiraterone and enzalutamide have largely replaced ketoconazole as oral treatments for castration‐resistant prostate cancer (CRPC). We investigated the differential adoption of abiraterone and enzalutamide across facilities in a national healthcare system to understand the impact a facility has on the receipt of these novel therapies. Methods Using data from the VA Corporate Data Warehouse, we identified a cohort of men with CRPC who received the most common first‐line therapies: abiraterone, enzalutamide, docetaxel, or ketoconazole between 2010 and 2017. We described variability in the adoption of abiraterone and enzalutamide across facilities by time period (2010–2013 or 2014–2017). We categorized facilities depending on the timing of adoption of abiraterone and enzalutamide relative to other facilities and described facility characteristics associated with early and late adoption. Results We identified 4998 men treated with ketoconazole, docetaxel, abiraterone, or enzalutamide as first‐line CRPC therapy between 2010 and 2017 at 125 national facilities. When limiting the cohort to oral therapies, most patients treated earlier in the study period (2010–2013) received ketoconazole. A dramatic shift was seen by the second half of the study period (2014–2017) with most men treated with first‐line abiraterone (61%). Despite this shift and a new standard of care, some facilities persisted in the widespread use of ketoconazole in the later period, so‐called late adopting facilities. After multivariable adjustment, patients who received treatment at a late adopting facility were more likely receiving care at a lower complexity, rural facility, with less urology and hematology/oncology workforce (all p

Objective To describe people with gout who were diagnosed with coronavirus disease 2019 (COVID‐19) and hospitalized and to characterize their outcomes. Methods Data on patients with gout hospitalized for COVID‐19 between March 12, 2020, and October 25, 2021, were extracted from the COVID‐19 Global Rheumatology Alliance registry. Descriptive statistics were used to describe the demographics, comorbidities, medication exposures, and COVID‐19 outcomes including oxygenation or ventilation support and death. Results One hundred sixty‐three patients with gout who developed COVID‐19 and were hospitalized were included. The mean age was 63 years, and 85% were male. The majority of the group lived in the Western Pacific Region (35%) and North America (18%). Nearly half (46%) had two or more comorbidities, with hypertension (56%), cardiovascular disease (28%), diabetes mellitus (26%), chronic kidney disease (25%), and obesity (23%) being the most common. Glucocorticoids and colchicine were used pre‐COVID‐19 in 11% and 12% of the cohort, respectively. Over two thirds (68%) of the cohort required supplemental oxygen or ventilatory support during hospitalization. COVID‐19‐related death was reported in 16% of the overall cohort, with 73% of deaths documented in people with two or more comorbidities. Conclusion This cohort of people with gout and COVID‐19 who were hospitalized had high frequencies of ventilatory support and death. This suggests that patients with gout who were hospitalized for COVID‐19 may be at risk of poor outcomes, perhaps related to known risk factors for poor outcomes, such as age and presence of comorbidity.

Objective Some patients with rheumatic diseases might be at higher risk for coronavirus disease 2019 (COVID‐19) acute respiratory distress syndrome (ARDS). We aimed to develop a prediction model for COVID‐19 ARDS in this population and to create a simple risk score calculator for use in clinical settings. Methods Data were derived from the COVID‐19 Global Rheumatology Alliance Registry from March 24, 2020, to May 12, 2021. Seven machine learning classifiers were trained on ARDS outcomes using 83 variables obtained at COVID‐19 diagnosis. Predictive performance was assessed in a US test set and was validated in patients from four countries with independent registries using area under the curve (AUC), accuracy, sensitivity, and specificity. A simple risk score calculator was developed using a regression model incorporating the most influential predictors from the best performing classifier. Results The study included 8633 patients from 74 countries, of whom 523 (6%) had ARDS. Gradient boosting had the highest mean AUC (0.78; 95% confidence interval [CI]: 0.67‐0.88) and was considered the top performing classifier. Ten predictors were identified as key risk factors and were included in a regression model. The regression model that predicted ARDS with 71% (95% CI: 61%‐83%) sensitivity in the test set, and with sensitivities ranging from 61% to 80% in countries with independent registries, was used to develop the risk score calculator. Conclusion We were able to predict ARDS with good sensitivity using information readily available at COVID‐19 diagnosis. The proposed risk score calculator has the potential to guide risk stratification for treatments, such as monoclonal antibodies, that have potential to reduce COVID‐19 disease progression.

Objective Patients with immune‐mediated diseases treated with anti‐CD20 monoclonal antibodies may have worse coronavirus disease 2019 (COVID‐19) outcomes due to impaired humoral immunity, but differences compared with the general population are unknown. Methods We identified patients with immune‐mediated diseases who received anti‐CD20 monoclonal antibodies within 1 year prior to the index date of polymerase chain reaction–confirmed COVID‐19 between January 31, 2020, and January 31, 2021. General population comparators with COVID‐19 were matched up 5:1 by age, sex, and polymerase chain reaction date. Unadjusted and multivariable adjusted (for age, race, body mass index, and Charlson Comorbidity Index) hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in recipients of anti‐CD20 monoclonal antibodies versus comparators were estimated by using Cox regression. Results We identified 114 cases patients COVID‐19 who had received anti‐CD20 monoclonal antibodies for immune‐mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID‐19 (mean age 54 years, 70% female). Patients treated with anti‐CD20 monoclonal antibodies had higher mortality (adjusted HR 2.16; 95% CI: 1.03‐4.54) than matched comparators. Risks of hospitalization (adjusted HR 0.88; 95% CI: 0.62‐1.26) and mechanical ventilation use (adjusted HR 0.82; 95% CI: 0.36‐1.87) were similar. Similar trends were seen in analyses according to type of indication (eg, rheumatic or neurologic disease) and duration of anti‐CD20 monoclonal antibody use (

Objective To evaluate the impact of telemedicine use during the coronavirus disease 2019 (COVID‐19) pandemic on rheumatology trainees. Methods A voluntary, anonymous, web‐based survey was administered in English, Spanish, or French from August 19 to October 5, 2020. Adult and pediatric rheumatology trainees were invited to participate via social media and email. Using multiple‐choice questions and Likert scales, the survey assessed prior and current telemedicine use, impact on training, and supervision after COVID‐19 prompted rapid telemedicine implementation. Results Surveys were received from 302 trainees from 33 countries, with 83% in adult rheumatology training programs. Reported telemedicine use increased from 13% before the pandemic to 82% during the pandemic. United States trainees predominantly used video visits, whereas outside the United States telemedicine was predominantly audio only. Most (65%) evaluated new patients using telemedicine. More respondents were comfortable using telemedicine for follow‐up patients (69%) than for new patients (25%). Only 39% of respondents reported receiving telemedicine‐focused training, including instruction on software, clinical skills, and billing, whereas more than half of United States trainees (59%) had training. Postconsultation verbal discussion was the most frequent form of supervision; 24% reported no supervision. Trainees found that telemedicine negatively impacted supervision (50%) and the quality of clinical teaching received (70%), with only 9% reporting a positive impact. Conclusions Despite widespread uptake of telemedicine, a low proportion of trainees received telemedicine training, and many lacked comfort in evaluating patients, particularly new patients. Inadequate supervision and clinical teaching were areas of concern. If telemedicine remains in widespread use, ensuring appropriate trainee supervision and teaching should be prioritized.

Abstract Purpose This study aims to determine whether there is consensus regarding staging and management of cutaneous squamous cell carcinoma (CSCC) across the various specialties that manage this disease. Materials and Methods A survey regarding CSCC high‐risk features, staging, and management was created and emailed to cutaneous oncology experts including dermatology, head and neck surgery/surgical oncology, radiation oncology, and medical oncology. Results One hundred fifty‐six (46%) of 357 invited physicians completed the survey. Depth of invasion (92%), perineural invasion (99%), histologic differentiation (85%), and patient immunosuppression (90%) achieved consensus (>80%) as high‐risk features of CSCC. Dermatologists were more likely to also choose clinical tumor diameter (79% vs. 54%) and histology (99% vs. 66%) as a high‐risk feature. Dermatologists were also more likely to utilize the Brigham and Women's Hospital (BWH) staging system alone or in conjunction with American Joint Committee on Cancer (AJCC) (71%), whereas other cancer specialists (OCS) tend to use only AJCC (71%). Respondents considered AJCC T3 and higher (90%) and BWH T2b and higher (100%) to be high risk and when they consider radiologic imaging, sentinel lymph node biopsy, post‐operative radiation therapy, and increased follow‐up. Notably, a large number of respondents do not use staging systems or tumor stage to determine treatment options beyond surgery in high‐risk CSCC. Conclusion This survey study highlights areas of consensus and differences regarding the definition of high‐risk features of CSCC, staging approaches, and management patterns between dermatologists and OCS. High‐risk CSCC is defined as, but not limited to, BWH T2b and higher and AJCC T3 and higher, and these thresholds can be used to identify cases for which treatment beyond surgery may be considered. Dermatologists are more likely to utilize BWH staging, likely because BWH validation studies showing advantages over AJCC were published in dermatology journals and discussed at dermatology meetings. Additional data are necessary to develop a comprehensive risk‐based management approach for CSCC.

The migration phase of birds is divided into two main states: stopovers and actual migratory flights. For soaring birds, such as storks, nighttime is especially important to conserve energy and to start the next day in favourable weather conditions. Although there is a large number of recent studies on white stork Ciconia ciconia, for example using advanced technologies such as GPS technology, the nocturnal behaviour of the species is still an enigma. Thus, we GSM–GPS‐tagged 90 immature storks and checked their nocturnal behaviour, especially roost disturbance, during their first autumn migration from breeding grounds in southern Poland to wintering places in Africa. Storks roosted on three types of site: on buildings, on the ground or in trees. Birds that roosted on the ground had a higher probability of nighttime disturbance than those that used trees or buildings. The probability of disturbance at night was also related to longitude and latitude; the most easterly birds and those at the start of the migration route were disturbed more often during the night. Furthermore, and interestingly, environmental conditions at roosts were also significantly related to the probability of disturbance; birds roosting at tree sites with higher NDVI (greener) and with higher levels of artificial light both had a lower probability of disturbance. A possible explanation of this could be related to lower potential predatory pressure at night. We found that after long flights birds were disturbed more often at night, and that disturbed birds migrated further the next day. For a better understanding of the nocturnal behaviour of storks, as well as of other migratory birds, the use of modern technological tools with greater precision is recommended.

Background A beneficial role for prostanoids in hypertension is suggested by clinical studies showing nonsteroidal anti‐inflammatory drugs, which block the production of all prostanoids, cause sodium retention and exacerbate hypertension. Among prostanoids, prostaglandin E2 and its E‐prostanoid receptor 4 receptor (EP4R) have been implicated in blood pressure control. Our previous study found that conditional deletion of EP4R from all tissues in adult mice exacerbates angiotensin II‐dependent hypertension, suggesting a powerful effect of EP4R to resist blood pressure elevation. We also found that elimination of EP4R from vascular smooth muscle cells did not affect the severity of hypertension, suggesting nonvascular targets of prostaglandin E mediate this antihypertensive effect. Methods and Results Here we generated mice with cell‐specific deletion of EP4R from macrophage‐specific EP4 receptor knockouts or kidney epithelial cells (KEKO) to assess the contributions of EP4R in these cells to hypertension pathogenesis. Macrophage‐specific EP4 receptor knockouts showed similar blood pressure responses to alterations in dietary sodium or chronic angiotensin II infusion as Controls. By contrast, angiotensin II‐dependent hypertension was significantly augmented in KEKOs (mean arterial pressure: 146±3 mm Hg) compared with Controls (137±4 mm Hg; P=0.02), which was accompanied by impaired natriuresis in KEKOs. Because EP4R expression in the kidney is enriched in the collecting duct, we compared responses to amiloride in angiotensin II‐infused KEKOs and Controls. Blockade of the epithelial sodium channel with amiloride caused exaggerated natriuresis in KEKOs compared with Controls (0.21±0.01 versus 0.15±0.02 mmol/24 hour per 20 g; P=0.015). Conclusions Our data suggest EP4R in kidney epithelia attenuates hypertension. This antihypertension effect of EP4R may be mediated by reducing the activity of the epithelial sodium channel, thereby promoting natriuresis.

Abstract The resistance of pest species to chemical controls has vast ecological, economic, and societal costs. In most cases, resistance is only detected after spreading throughout an entire population. Detecting resistance in its incipient stages, by comparison, provides time to implement preventative strategies. Incipient resistance can be detected by coupling standard toxicology assays with large‐scale gene expression experiments. We apply this approach to a system where an invasive parasite, sea lamprey (Petromyzon marinus), has been treated with the highly effective pesticide 3‐trifluoromethyl‐4‐nitrophenol (TFM) for 60 years. Toxicological experiments revealed that lamprey from treated populations did not have higher survival to TFM exposure than lamprey from untreated populations, demonstrating that full‐fledged resistance has not yet evolved. In contrast, we find hundreds of genes differentially expressed in response to TFM in the population with the longest history of exposure, many of which relate to TFM’s primary mode of action, the uncoupling of oxidative phosphorylation, and subsequent depletion of ATP. Three genes critical to oxidative phosphorylation, ATP5PB, PLCB1, and NDUFA9, were nearly fixed for alternative alleles in comparisons of SNPs between treated and untreated populations (FST > 5 SD from the mean). ATP5PB encodes subunit b of ATP synthase and an additional subunit, ATP5F1B, was canalized for high expression in treated populations, but remained plastic in response to TFM treatment in individuals from the untreated population. These combined genomic and transcriptomic results demonstrate that an adaptive, genetic response to TFM is likely driving incipient resistance in a damaging pest species.

Abstract Background Lumbar syringomyelia (SM), lumbosacral pain, and more caudal spinal cord termination are reported in Cavalier King Charles spaniels (CKCS). Data are lacking on the clinical relevance of alterations in their spinal cord terminal structures. Objectives To compare spinal cord termination level and filum terminale internum length (FTIL) with presence of lumbar SM and clinical signs in CKCS. Animals Forty‐eight CKCS. Methods In this prospective study, pain was quantified using owner and clinician assessments. Vertebral level of spinal cord and dural sac termination, presence of SM, and FTIL were determined from sagittal magnetic resonance imaging (MRI) sequences. Kappa and intraclass correlation (ICC) analyses determined interobserver reliability. The MRI findings were compared to owner and clinician‐reported pain quantification. Results Interobserver reliability was good for spinal cord and dural sac termination (kappa = 0.61 and 0.64, respectively) and excellent for FTIL (ICC: 92% agreement). The spinal cord terminated at 6th lumbar vertebra in 1, 7th lumbar vertebra in 31, and the sacrum in 15 dogs, and termination level was associated with lumbar SM (P = .002) but not clinical signs. Mean FTIL was 2.9 ± 1.08 mm; it was associated with owner‐reported pain (P = .033) and spinal palpation scores (P = .023). Painful CKCS without SM had shorter FTIL compared to normal CKCS and painful CKCS with SM (P = .02). Conclusions Painful CKCS without SM have decreased distance between the termination of the spinal cord and dural sac, suggesting a shorter FTIL. More caudal spinal cord termination is associated with development of lumbar SM.

Abstract The current COVID‐19 pandemic has forced the global higher education community to rapidly adapt to partially or fully online course offerings. For field‐ or laboratory‐based courses in ecological curricula, this presents unique challenges. Fortunately, a diverse set of active learning techniques exists, and these techniques translate well to online settings. However, limited guidance and resources exist for developing, implementing, and evaluating active learning assignments that fulfill specific objectives of ecology‐focused courses. To address these informational gaps, we (a) identify broad learning objectives across a variety of ecology‐focused courses, (b) provide examples, based on our collective online teaching experience, of active learning activities that are relevant to the identified ecological learning objectives, and (c) provide guidelines for successful implementation of active learning assignments in online courses. Using The Wildlife Society's list of online higher education ecology‐focused courses as a guide, we obtained syllabi from 45 ecology‐focused courses, comprising a total of 321 course‐specific learning objectives. We classified all course‐specific learning objectives into at least one of five categories: (a) Identification, (b) Application of Concepts/Hypotheses/Theories, (c) Management of Natural Resources, (d) Development of Professional Skills, or (e) Evaluation of Concepts/Practices. We then provided two examples of active learning activities for each of the five categories, along with guidance on their implementation in online settings. We suggest that, when based on sound pedagogy, active learning techniques can enhance the online student's experience by activating ecological knowledge.

Abstract Mean annual temperature (MAT) is an influential climate factor affecting the bioavailability of growth‐limiting nutrients nitrogen (N) and phosphorus (P). In tropical montane wet forests, warmer MAT drives higher N bioavailability, while patterns of P availability are inconsistent across MAT. Two important nutrient acquisition strategies, fine root proliferation into bulk soil and root association with arbuscular mycorrhizal fungi, are dependent on C availability to the plant via primary production. The case study presented here tests whether variation in bulk soil N bioavailability across a tropical montane wet forest elevation gradient (5.2°C MAT range) influences (a) morphology fine root proliferation into soil patches with elevated N, P, and N+P relative to background soil and (b) arbuscular mycorrhizal fungal (AMF) colonization of fine roots in patches. We created a fully factorial fertilized root ingrowth core design (N, P, N+P, unfertilized control) representing soil patches with elevated N and P bioavailability relative to background bulk soil. Our results show that percent AMF colonization of roots increased with MAT (r2 = .19, p = .004), but did not respond to fertilization treatments. Fine root length (FRL), a proxy for root foraging, increased with MAT in N+P‐fertilized patches only (p = .02), while other fine root morphological parameters did not respond to the gradient or fertilized patches. We conclude that in N‐rich, fine root elongation into areas with elevated N and P declines while AMF abundance increases with MAT. These results indicate a tradeoff between P acquisition strategies occurring with changing N bioavailability, which may be influenced by higher C availability with warmer MAT.

Objective The recent hydroxychloroquine (HCQ) shortage due to use in coronavirus disease 2019 (COVID‐19) has forced some rheumatic disease patients to choose between continuing their current dose of HCQ but exhaust their supply early or ration it in order to prolong its use. Blood HCQ concentrations are directly correlated with disease activity in rheumatic diseases such as systemic lupus erythematosus. We sought to model how changes in HCQ dosage will best maintain sufficient blood HCQ concentrations for the longest period of time in order to avoid potential future flares. Methods A one‐compartment pharmacokinetic model was used to predict mean blood HCQ concentrations. Monte Carlo simulations with 10‐fold inflated model parameter variance was utilized to assess the impact of variability. Results Maintenance of 400 mg/d resulted in mean therapeutic whole‐blood HCQ concentrations that exceeded 700 ng/ml for 10.5 days, whereas HCQ rationing by reducing the dose by half resulted in the mean concentration remaining above 700 ng/ml for 2.4 days (net gain = 8 days). Variability analysis demonstrates that results may differ at the individual level, dependent on baseline blood HCQ concentrations. Conclusion Although mean blood concentrations exceed 700 ng/ml for a longer time if patients maintain their full dose of HCQ, more information is needed to fully understand the elimination of HCQ at the patient level, particularly the contribution of tissue stores of HCQ transiting back into the blood.

Abstract State fish and wildlife agencies in the United States are confronted with the realities of a rapidly changing society. With declines in historical sources of revenue and the growth of diverse voices with values that differ from those emphasized by traditional policies and user groups, agencies are faced with diminishing relevancy and are encountering institutional challenges that inhibit their ability to serve the broader public. Here, in collaboration with a group of fish and wildlife agency leaders from 11 states, conservation professionals, and academics, we employ qualitative methods and concepts from systems theory to develop an integrative model of a state wildlife agency. We use this model to identify leverage points to induce transformational change toward an ideal future state: one driven by a system of shared values toward wildlife and a mission to improve quality of life for all people. Our findings point to the importance of developing interventions that will lead to changes in agency culture, systems of governance, and policy and action, and enhance the accessibility of natural resources and opportunities for diverse publics to engage with and benefit from fish and wildlife. We offer recommendations for state wildlife agencies to engage in adaptive organizational change and for university programs to support agency needs.

Abstract As practitioners of mitigation and conservation of bats, we think use of artificial bat roosts contribute to bat conservation and should be encouraged. Problems with boxes identified by Reed and O'Keefe also exist with natural roosts, and they are more readily studied and managed with artificial than natural roosts. Use of boxes also provides an opportunity for citizen science, but more importantly engenders citizen conservation.

Abstract Despite the importance of species–area relationships (SARs) to conservation, SARs in human‐fragmented rivers have received little attention. Our aim was to test for the presence and strength of SARs for littoral fish assemblages of an extensively dammed river in south‐central Ontario, Canada, and to examine long‐running hypotheses for the drivers of SARs. Twenty‐six navigational dams with locks built between 1837 and 1913 occur along the 160 km length of the Trent River examined in this study. We evaluated the relationship between richness and fragment area, and then used linear models to test whether the area per se, habitat diversity, or other hypotheses were best supported by the data. A power–function relationship with area explained 46% of the variation in fish species richness, and the slope (z = 0.4) was high compared with SARs reported from other ecosystems, indicating that species accumulated rapidly with an increase in fragment area. Multi‐predictor models suggested that area was significantly related to richness, but that vegetation cover diversity had a stronger relative effect. The slope of our SAR may indicate that there is a high degree of isolation between populations in different fragments, even though the lock system reportedly allows some passage of organisms. Our findings also suggest that mitigating against local extinction due to small population sizes (i.e., area effects), and enhancing aquatic vegetation cover may be viable strategies for promoting species diversity in the study river. Studies of SARs in fragmented rivers may offer additional benefits to supporting restoration planning where efforts are being made to increase species diversity.

Plant mechanical failure, also known as lodging, is the cause of significant and unpredictable yield losses in cereal crops. Lodging occurs in two distinct failure modes—stalk lodging and root lodging. Despite the prevalence and detrimental impact of lodging on crop yields, there is little consensus on how to phenotype plants in the field for lodging resistance and thus breed for mechanically resilient plants. This review provides an overview of field‐based mechanical testing approaches to assess stalk and root lodging resistance. These approaches are placed in the context of future perspectives. Best practices and recommendations for acquiring field‐based mechanical phenotypes of plants are also presented.

Abstract Introduction Past research has suggested that reading disability is a complex disorder involving genetic and environment contributions, as well as gene–gene and gene–environment interaction, but to date little is known about the underlying mechanisms. Method Using the Avon Longitudinal Study of Parents and Children, we assessed the contributions of genetic, demographic, and environmental variables on case–control status using machine learning. We investigated the functional interactions between genes using pathway and network analysis. Results Our results support a systems approach to studying the etiology of reading disability with many genes (e.g., RAPGEF2, KIAA0319, DLC1) and biological pathways (e.g., neuron migration, positive regulation of dendrite regulation, nervous system development) interacting with each other. We found that single nucleotide variants within genes often had opposite effects and that enriched biological pathways were mediated by neuron migration. We also identified behavioral (i.e., receptive language, nonverbal intelligence, and vocabulary), demographic (i.e., mother's highest education), and environmental (i.e., birthweight) factors that influenced case–control status when accounting for genetic information. Discussion The behavioral and demographic factors were suggested to be protective against reading disability status, while birthweight conveyed risk. We provided supporting evidence that reading disability has a complex biological and environmental etiology and that there may be a shared genetic and neurobiological architecture for reading (dis)ability.

Abstract Exercise training and physical activity are known to be associated with high mitochondrial content and oxidative capacity in skeletal muscle. Metabolic diseases including obesity and insulin resistance are associated with low mitochondrial capacity in skeletal muscle. Certain transcriptional factors such as PGC‐1α are known to mediate the exercise response; however, the precise molecular mechanisms involved in the adaptation to exercise are not completely understood. We performed multiple measurements of mitochondrial capacity both in vivo and ex vivo in lean or overweight individuals before and after an 18‐day aerobic exercise training regimen. These results were compared to lean, active individuals. Aerobic training in these individuals resulted in a marked increase in mitochondrial oxidative respiratory capacity without an appreciable increase in mitochondrial content. These adaptations were associated with robust transcriptome changes. This work also identifies the Tribbles pseudokinase 1, TRIB1, as a potential mediator of the exercise response in human skeletal muscle.

Abstract Availability of time series data in different domains has resulted in approaches for outbreak detection. A popular alternative to detect outbreaks is to use daily counts of events. However, time between events (TBE) has proven to be a useful alternative, especially in the case of sudden, unexpected events. Past work that uses TBE for monitoring events assumes that the in‐control number of events is up to 10 per day. In this article, we derive robust monitoring plans that are scalable when the in‐control counts are higher than 10 per day but less than 100 per counting period (eg, day). TBE values are generally nonhomogeneous across days and within days. This makes the volume of data to train the technology a challenge, and this challenge increases the volume of data needed to design the charts. This article discusses these challenges and suggests solutions for data that are known to be Weibull‐distributed. We present our results in two parts. The first is a simulated dataset that controls parameters of the plan such as the daily counts of events. We then show how the monitoring plans can be applied to the detection of syndromes (ie, disease outbreaks) using social media data.

Abstract Locations where populations are most reliant on forests and their ecosystem services for subsistence and development are also areas where modern slavery persists. These issues are noted within the Sustainable Development Goals (SDGs), both target 15.2 and 8.7 respectively. Often activities using slavery perpetuate deforestation, bolstering a slavery‐environment nexus; which has been examined by comparing modern slavery estimates against environmental protection levels. This study assesses the relationship between tree loss and modern slavery focusing on four countries: Brazil, Ghana, Indonesia, and Mozambique. Previously mapped levels of tree loss and predicted future levels of loss have been compared against modern slavery estimates from the Global Slavery Index 2016 and illegal logging analyses to determine an estimate of the risk for slavery related tree loss. These results provide an insight in to the co‐occurrence between modern slavery and tree loss due to a number of activities that are highlighted, including mining, illegal logging, and agricultural practices. The co‐occurrence is both complex, and yet, beyond coincidental. Implications for both national and global policy are noted assessing the benefits that could be achieved by limiting tree loss and ending modern slavery; of benefit to both the conservation and antislavery communities.