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Objectives: An accident during arboreal locomotion can lead to risky falls, but it remains unclear that the extent to which primates, as adept arborealists, change their locomotion in response to the perceived risk of moving on high supports in the tree canopy. By using more stable forms of locomotion on higher substrates, primates might avoid potentially fatal consequences. Materials and Methods: Using high‐speed cameras, we recorded the quadrupedal locomotion of four wild lemur species—Eulemur rubriventer, Eulemur rufifrons, Hapalemur aureus, and Lemur catta (N = 113 total strides). We quantified the height, diameter, and angular orientation of locomotor supports using remote sensors and tested the influence of support parameters on gait kinematics, specifically predicting that in response to increasing substrate height, lemurs would decrease speed and stride frequency, but increase stride length and the mean number of supporting limbs. Results: Lemurs did not adjust stride frequency on substrates of varying height. Adjustments to speed, stride length, and the mean number of supporting limbs in response to varying height often ran counter to predictions. Only E. rubriventer decreased speed and increased the mean number of supporting limbs on higher substrates. Discussion: Results suggest that quadrupedal walking is a relatively safe form of locomotion for lemurs, requiring subtle changes in gait to increase stability on higher—that is, potentially riskier—substrates. Continued investigation of the impact of height on locomotion will be important to determine how animals assess risk in their environment and how they choose to use this information to move more safely. Research Highlights: Substrate height can increase the risk of injury after a fall.Lemurs make subtle and variable adjustments to gait in response to substrate height.Substrate height will be important to include in future studies of wild primate locomotion. [ABSTRACT FROM AUTHOR]

Additional immunomodulatory treatment is needed for the management of immune‐mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses. The aim of this study was to evaluate the pharmacokinetics of a single dose of MMF in healthy horses in the fed vs. fasted state. Six healthy Standardbred mares were administered MMF 10 mg/kg by a nasogastric (NG) tube in a fed and fasted state. A six‐day washout period was performed between the two doses. No statistically significant differences in mycophenolic acid (MPA) concentrations were seen at any time point apart from 8 h, when plasma metabolite concentrations were significantly higher in the fasted state compared to the fed state (p =.038). Evidence of enterohepatic recirculation was seen only in the fasted state; this did not yield clinical differences in horses administered a single‐dose administration but may be significant in horses receiving long‐term MMF treatment. [ABSTRACT FROM AUTHOR]

Environmental changes associated with rapid climate change in the Arctic, such as the increased rates of sedimentation from climatic or anthropogenic sources, can enhance the impact of abiotic stressors on coastal ecosystems. High sedimentation rates can be detrimental to nearshore kelp abundance and distribution, possibly due to increased mortality at the spore settlement stage. Spore settlement and viability of the Arctic kelp Laminaria solidungula were examined through a series of lab‐based sedimentation experiments. Spores were exposed to increasing sediment loads in three experimental designs simulating different sedimentation scenarios: sediment deposition above settled spores, settlement of spores on sediment‐covered substrate, and simultaneous suspension of spores and sediments during settlement. Spore settlement was recorded upon completion of each experiment, and gametophyte abundance was assessed following a growth period with sediments removed to examine short‐term spore viability via a gametophyte‐to‐settled‐spore ratio. In all three types of sediment exposure, the addition of sediments caused a 30%–40% reduction in spore settlement relative to a no‐sediment control. Spore settlement decreased significantly between the low and high sediment treatments when spores were settled onto sediment‐covered substrates. In all experiments, increasing amounts of sediment had no significant effect on spore viability, indicating that spores that had settled under different short‐term sediment conditions were viable. Our results indicate that depending on spore‐sediment interaction type, higher rates of sedimentation resulting from increased sediment loading could affect L. solidungula spore settlement success with potential impacts on the long‐term persistence of a diverse and productive benthic habitat. [ABSTRACT FROM AUTHOR]

Background: Image quality evaluation of prostate MRI is important for successful implementation of MRI into localized prostate cancer diagnosis. Purpose: To examine the impact of image quality on prostate cancer detection using an in‐house previously developed artificial intelligence (AI) algorithm. Study Type: Retrospective. Subjects: 615 consecutive patients (median age 67 [interquartile range [IQR]: 61–71] years) with elevated serum PSA (median PSA 6.6 [IQR: 4.6–9.8] ng/mL) prior to prostate biopsy. Field Strength/Sequence: 3.0T/T2‐weighted turbo‐spin‐echo MRI, high b‐value echo‐planar diffusion‐weighted imaging, and gradient recalled echo dynamic contrast‐enhanced. Assessments: Scans were prospectively evaluated during clinical readout using PI‐RADSv2.1 by one genitourinary radiologist with 17 years of experience. For each patient, T2‐weighted images (T2WIs) were classified as high‐quality or low‐quality based on evaluation of both general distortions (eg, motion, distortion, noise, and aliasing) and perceptual distortions (eg, obscured delineation of prostatic capsule, prostatic zones, and excess rectal gas) by a previously developed in‐house AI algorithm. Patients with PI‐RADS category 1 underwent 12‐core ultrasound‐guided systematic biopsy while those with PI‐RADS category 2–5 underwent combined systematic and targeted biopsies. Patient‐level cancer detection rates (CDRs) were calculated for clinically significant prostate cancer (csPCa, International Society of Urological Pathology Grade Group ≥2) by each biopsy method and compared between high‐ and low‐quality images in each PI‐RADS category. Statistical Tests: Fisher's exact test. Bootstrap 95% confidence intervals (CI). A P value <0.05 was considered statistically significant. Results: 385 (63%) T2WIs were classified as high‐quality and 230 (37%) as low‐quality by AI. Targeted biopsy with high‐quality T2WIs resulted in significantly higher clinically significant CDR than low‐quality images for PI‐RADS category 4 lesions (52% [95% CI: 43–61] vs. 32% [95% CI: 22–42]). For combined biopsy, there was no significant difference in patient‐level CDRs for PI‐RADS 4 between high‐ and low‐quality T2WIs (56% [95% CI: 47–64] vs. 44% [95% CI: 34–55]; P = 0.09). Data Conclusion: Higher quality T2WIs were associated with better targeted biopsy clinically significant cancer detection performance for PI‐RADS 4 lesions. Combined biopsy might be needed when T2WI is lower quality. Level of Evidence: 2 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Fish serve as indicators of exposure to contaminants of emerging concern (CECs)—chemicals such as pharmaceuticals, hormones, and personal care products—which are often designed to impact vertebrates. To investigate fish health and CECs in situ, we evaluated the health of wild fish exposed to CECs in waterbodies across northeastern Minnesota with varying anthropogenic pressures and CEC exposures: waterbodies with no human development along their shorelines, those with development, and those directly receiving treated wastewater effluent. Then, we compared three approaches to evaluate the health of fish exposed to CECs in their natural environment: a refined fish health assessment index, a histopathological index, and high‐throughput (ToxCast) in vitro assays. Lastly, we mapped adverse outcome pathways (AOPs) associated with identified ToxCast assays to determine potential impacts across levels of biological organization within the aquatic system. These approaches were applied to subsistence fish collected from the Grand Portage Indian Reservation and 1854 Ceded Territory in 2017 and 2019. Overall, 24 CECs were detected in fish tissues, with all but one of the sites having at least one detection. The combined implementation of these tools revealed that subsistence fish exposed to CECs had histological and macroscopic tissue and organ abnormalities, although a direct causal link could not be established. The health of fish in undeveloped sites was as poor, or sometimes poorer, than fish in developed and wastewater effluent‐impacted sites based on gross and histologic tissue lesions. Adverse outcome pathways revealed potential hazardous pathways of individual CECs to fish. A better understanding of how the health of wild fish harvested for consumption is affected by CECs may help prioritize risk management research efforts and can ultimately be used to guide fishery management and public health decisions. Integr Environ Assess Manag 2024;20:846–863. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Key Points: 1.Fish exposed to contaminants of emerging concern had histological and macroscopic tissue and organ abnormalities.2.Adverse outcome pathways revealed potential hazardous pathways of individual contaminants of emerging concern to fish.3.The health of fish in undeveloped sites was as poor, or sometimes poorer, than fish in developed and wastewater effluent‐impacted sites based on gross and histologic tissue lesions. [ABSTRACT FROM AUTHOR]

Aim: Low doses of lithium, as might be used for mood or dementia prevention, do not carry the same renal, toxicity, and tolerability problems of doses used for prophylaxis or treatment of mania. However, thyroid effects of low doses have not been investigated. Our goal in this study was to assess the changes in thyroid-stimulating hormone (TSH) associated with a broad range of lithium levels, including those well below the therapeutic range for bipolar disorders. Methods: This study was conducted in a small healthcare system with 19 associated primary care clinics served by a Collaborative Care program of psychiatric consultation. In this retrospective review of electronic records, we searched for patients who had received a lithium prescription and both pre- and post-lithium thyroid-stimulating hormone (TSH) levels. Results: Patients with low lithium levels (<0.5 mEq/L, N = 197) had a mean thyroidstimulating hormone (TSH) increase of 0.52 mIU/L. Patients with maintenance lithium levels (0.5-0.8 mEq/L; N = 123) had a mean TSH increase of 1.01 mIU/L; and patients with antimanic lithium levels (>0.8 mEq/L; N = 79) had a mean TSH increase of 2.16 mIU/L. The probability of TSH exceeding the upper limit of normal in our laboratory (>4.2 mIU/L) was positively associated with pre-lithium TSH. Conclusion: These results suggest that the risk of lithium-induced hypothyroidism is dose-related, and relatively small with very low doses, but thyroid monitoring, including a pre-lithium TSH, is still warranted. [ABSTRACT FROM AUTHOR]

Background: Firefighters are routinely exposed to loud noise that put them at risk for hearing loss. A reliable and valid measure to assess firefighters' hearing function is important. This study aims to test the reliability and validity of the modified Amsterdam Inventory for Auditory Disability and Handicap ((m)AIADH) in firefighters. Method: A cross‐sectional study was conducted using a convenience sample of 239 career firefighters from six partnered fire departments in Central Texas and Northern California. The internal consistency, convergent and criterion validity, and the ability to discriminate groups by measured hearing, perceived hearing, and a combination of measured and perceived hearing, were examined using the total score and score for each of the five subscales of the (m)AIADH. Results: The study participants were primarily men (93%). Satisfactory internal consistency was revealed for the (m)AIADH with Cronbach's alpha above 0.80 for all five subscales. Criterion analysis presented a moderate correlation between the (m)AIADH and the average of hearing threshold at high frequencies (4, 6, and 8 kHz). For convergent validity, the (m)AIADH was moderately to highly related with perceived hearing. There were statistically significant differences in the total (m)AIADH score and the five subscales for measured hearing thresholds except for "intelligibility in quiet." The (m)AIADH also showed a discriminative ability to distinguish between the group with good perceived hearing and the group with bad perceived hearing. Conclusion: The (m)AIADH is a reliable and valid measure to assess various dimensions of hearing function among firefighters. [ABSTRACT FROM AUTHOR]

Culturally responsive personalized learning (CRPL) emphasizes the importance of aligning personalized learning approaches with previous research on culturally responsive practices to consider social, cultural, and linguistic contexts for learning. In the present discussion, we briefly summarize two bodies of literature considered in defining and developing a framework for CRPL: technology‐enabled personalized learning and culturally relevant, responsive, and sustaining pedagogy. We then provide a definition and framework consisting of six key principles of CRPL, along with a brief discussion of theories and empirical evidence to support these principles. These six principles include agency, dynamic adaptation, connection to lived experiences, consideration of social movements, opportunities for collaboration, and shared power. These principles fall into three domains: fostering flexible student‐centered learning experiences, leveraging relevant content and practices, and supporting meaningful interactions within a community. Finally, we conclude with some implications of this framework for researchers, policymakers, and practitioners working to ensure that all students receive high‐quality learning opportunities that are both personalized and culturally responsive. Report Number: RR‐23‐09 [ABSTRACT FROM AUTHOR]

This report presents results from a survey of 64 elementary mathematics and reading language arts teacher educators providing feedback on a new type of short performance task. The performance tasks each present a brief teaching scenario and then require a short performance as if teaching actual students. Teacher educators participating in the study first reviewed six performance tasks, followed by a more in‐depth review of two of the tasks. After reviewing the tasks, teacher educators completed an online survey providing input on the value of the tasks and on potential uses to support teacher preparation. The survey responses were positive with the majority of teacher educators supporting a variety of different uses of the performance tasks to support teacher preparation. The report concludes by proposing a larger theory for how the performance tasks can be used as both formative assessment tools to support teacher learning and summative assessments to guide decisions about candidates' readiness for the classroom. Report Number: RR‐23‐08 [ABSTRACT FROM AUTHOR]

Aim: Eurasian grapevine (Vitis vinifera), one of the most important fruit crops worldwide, diverged from its wild and currently endangered relative (V. vinifera ssp. sylvestris) about 11,000 years ago. In the 19th century, detrimental phylloxera and disease outbreaks in Europe forced grapevine cultivation to use American Vitis species as rootstocks, which have now become naturalized in Europe and are starting to colonize similar habitats to the wild grapevine. Accordingly, wild grapevine now faces two additional threats: the expansion of vineyards and invasive rootstocks. Furthermore, climate change is expected to have significant impacts on the distribution of all grapevines in Europe. In this study, we quantified the distributional and bioclimatic overlap between grapewine's wild relative and the taxa associated with viticulture, under current and future climate. Location: Europe, North America. Methods: The distributions of wild Eurasian grapevine, cultivated Eurasian grapevine and five American grapevine species used in rootstock breeding programs were linked to climate variables to model their bioclimatic niches. These ecological niche models were used to quantify the spatial and bioclimatic overlap between these seven Vitis taxa in Europe. Results: Niche and spatial overlap is high between the wild, cultivated and rootstock grapevines, suggesting that existing conflicts between vineyards and wild grapevine conservation may be further complicated by naturalized rootstocks outcompeting the wild grapevine, especially under future scenarios of climate change. In the hottest scenario, only 76.1% of the current distribution of the Eurasian grapevine remains in suitable area. Main Conclusions: As wild grapevine may ultimately provide a valuable gene pool for adapting viticulture to a changing world, these findings demonstrate the need for improved management of the wild grapevine and its natural habitat, to counteract the harmful effects of global change on the wild relatives of viticulture. [ABSTRACT FROM AUTHOR]

Thrombomodulin is important for the production of activated protein C (APC), a molecule with significant regulatory roles in coagulation and inflammation. To address known molecular incompatibilities between pig thrombomodulin and human thrombin that affect the conversion of protein C into APC, GalTKO.hCD46 pigs have been genetically modified to express human thrombomodulin (hTBM). The aim of this study was to evaluate the impact of transgenic hTBM expression on the coagulation dysregulation that is observed in association with lung xenograft injury in an established lung perfusion model, with and without additional blockade of nonphysiologic interactions between pig vWF and human GPIb axis. Expression of hTBM was variable between pigs at the transcriptional and protein level. hTBM increased the activation of human protein C and inhibited thrombosis in an in vitro flow perfusion assay, confirming that the expressed protein was functional. Decreased platelet activation was observed during ex vivo perfusion of GalTKO.hCD46 lungs expressing hTBM and, in conjunction with transgenic hTBM, blockade of the platelet GPIb receptor further inhibited platelets and increased survival time. Altogether, our data indicate that expression of transgenic hTBM partially addresses coagulation pathway dysregulation associated with pig lung xenograft injury and, in combination with vWF‐GP1b‐directed strategies, is a promising approach to improve the outcomes of lung xenotransplantation. [ABSTRACT FROM AUTHOR]

Objectives: Posttraumatic stress disorder (PTSD) is associated with sleep disturbances including insomnia and nightmares. This study compared cognitive behavioral therapy for insomnia (CBT‐I) with CBT‐I combined with imagery rehearsal therapy (IRT) for nightmares to evaluate if the combined treatment led to greater reductions in trauma‐related sleep disturbances in Australian veterans. Methods: Veterans with diagnosed PTSD, high insomnia symptom severity, and nightmares (N = 31) were randomized to eight group CBT‐I sessions or eight group CBT‐I + IRT sessions. Self‐reported sleep, nightmare, and psychological measures (primary outcome: Pittsburgh Sleep Quality Index), and objective actigraphy data were collected; the effect of obstructive sleep apnea (OSA) risk on treatment outcomes was also examined. Results: No treatment condition effects were detected for the combined treatment compared to CBT‐I alone, and no moderating effect of OSA risk was detected. On average, participants from both groups improved on various self‐report measures over time (baseline to 3 months posttreatment). Despite the improvements, mean scores for sleep‐specific measures remained indicative of poor sleep quality. There were also no significant differences between the groups on the actigraphy indices. Conclusions: The findings indicate that there is potential to optimize both treatments for veterans with trauma‐related sleep disturbances. [ABSTRACT FROM AUTHOR]

Theatre practitioners use empathy formation techniques within their acting methodology to develop particular characters for the stage. Here, Ann Phelps and Dylan Brown argue that, when Constantin Stanislavski's seminal dramatic method is placed in conversation with exemplarist moral theory, acting can become a tool for moral formation. To illustrate this claim, they describe their work with the Program for Leadership and Character at Wake Forest University, where a neo‐Aristotelian virtue ethics framework is embodied and expanded using this dramatic method. By using acting exercises to help students rehearse how their moral exemplars would respond to situations, Phelps and Brown challenge students to embody their exemplars instead of merely engaging with them as a passive intellectual exercise. Moral educators can achieve their pedagogical aim by expanding Stanislavski's dramatic "super‐objective" to encompass a "moral meta‐objective." This neo‐Aristotelian modification to Stanislavski's method might extend beyond the stage in ways that facilitate the embodiment of morally exemplary behavior, even after the curtain falls. [ABSTRACT FROM AUTHOR]

Small extracellular vesicles (EVs) have emerged as a focal point of EV research due to their significant role in a wide range of physiological and pathological processes within living systems. However, uncertainties about the nature of these vesicles have added considerable complexity to the already difficult task of developing EV‐based diagnostics and therapeutics. Whereas small EVs have been shown to be negatively charged, their surface charge has not yet been properly quantified. This gap in knowledge has made it challenging to fully understand the nature of these particles and the way they interact with one another, and with other biological structures like cells. Most published studies have evaluated EV charge by focusing on zeta potential calculated using classical theoretical approaches. However, these approaches tend to underestimate zeta potential at the nanoscale. Moreover, zeta potential alone cannot provide a complete picture of the electrical properties of small EVs since it ignores the effect of ions that bind tightly to the surface of these particles. The absence of validated methods to accurately estimate the actual surface charge (electrical valence) and determine the zeta potential of EVs is a significant knowledge gap, as it limits the development of effective label‐free methods for EV isolation and detection. In this study, for the first time, we show how the electrical charge of small EVs can be more accurately determined by accounting for the impact of tightly bound ions. This was accomplished by measuring the electrophoretic mobility of EVs, and then analytically correlating the measured values to their charge in the form of zeta potential and electrical valence. In contrast to the currently used theoretical expressions, the employed analytical method in this study enabled a more accurate estimation of EV surface charge, which will facilitate the development of EV‐based diagnostic and therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: Additional efficacious immunomodulatory treatment is needed for the management of immune‐mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses. Hypothesis/Objectives: To evaluate the pharmacokinetics (PK) of multiple‐day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen. Animals: Six healthy Standardbred mares. Methods: Horses received MMF 10 mg/kg PO q12h for 7 days in the fed state. Serial sampling was performed over 12 hours on Days 1 and 7 with trough samples collected every 24 hours, immediately before morning drug administration. Noncompartmental PK analyses were performed to determine primary PK parameters, followed by calculation of geometric means and coefficients of variation. A CBC, serum biochemical profile, physical examination, and fecal scoring were used to assess dose tolerability. Results: Seven days of treatment resulted in a mycophenolic acid (MPA) area under the curve (AUC0‐12) of 12 594 h × ng/mL (8567‐19 488 h × ng/mL) and terminal half‐life (T1/2) of 11.3 hours (7.5‐15.9 hours), yielding minor metabolite accumulation in all horses treated. Salmonellosis was detected in the feces of 2 horses by Day 7, and all horses developed myelosuppression, hyperbilirubinemia, hyporexia, decreased gastrointestinal motility, and decreased fecal output by the seventh day of treatment. Conclusion and Clinical Importance: Administration of MMF at 10 mg/kg PO q12h resulted in hematologic and clinical toxicity within 1 week of treatment. A decreased MMF dose, frequency, or both is needed to avoid colic. Drug monitoring should include frequent hemograms, serum biochemical profiles, and strict biosecurity protocols. [ABSTRACT FROM AUTHOR]

Inter‐particle secondary crosslinks allow microporous annealed particle (MAP) hydrogels to be formed. Methods to introduce secondary crosslinking networks in MAP hydrogels include particle jamming, annealing with covalent bonds, and reversible noncovalent interactions. Here, we investigate the effect of two different approaches to secondary crosslinking of polyethylene glycol (PEG) microgels via reversible guest‐host interactions. We generated a dual‐particle MAP‐PEG hydrogel using two species of PEG microgels, one functionalized with the guest molecule, adamantane, and the other with the host molecule, β‐cyclodextrin (Inter‐MAP‐PEG). In a different approach, a mono‐particle MAP‐PEG hydrogel was generated using one species of microgel functionalized with both guest and host molecules (Intra‐MAP‐PEG). The Intra‐MAP‐PEG formed a homogenous distribution due to the single type of microgels used. We then compared the mechanical properties of these two types of MAP‐PEG hydrogels and found that Intra‐MAP‐PEG resulted in significantly softer gels with lower yield stress. We investigated the effect of intra‐particle guest‐host interactions through titrated weight percentage and the concentration of functional groups added to the hydrogel. We found that there was an ideal concentration of guest‐host molecules that enables intra‐ and inter‐particle guest‐host interactions with sufficient covalent crosslinking. Based on these studies, Intra‐MAP‐PEG provides a homogeneous guest‐host hydrogel that is shear‐thinning with reversible secondary crosslinking. [ABSTRACT FROM AUTHOR]

Iododerma is a rare cutaneous eruption that manifests after exposure to iodine‐containing compounds, with few cases reported in the literature. Previous reports of this halogenoderma have described acellular halos simulating cryptococcus on histopathological examination but there is a paucity of reports of biopsies taken early in the disease course. We present a case of a 78‐year‐old patient who developed a papular eruption after receiving iodinated contrast. A skin biopsy taken within 24 h of the eruption showed a neutrophilic infiltrate with cryptococcal‐like acellular haloed structures, indicating that the diagnostic finding may be found early in the disease course. [ABSTRACT FROM AUTHOR]

Purpose: Pharmacists are integral members of the healthcare team, but interventions are not always captured due to documentation limitations. This study evaluated the impact of implementing a tracking tool to address gaps in capturing pharmacist interventions. Methods: A prospective, observational study was conducted to assess pharmacist interventions between July and November 2020. Twelve critical care pharmacists captured interventions on 10 weekdays using a tracking tool (iVent—Epic®) embedded in the electronic medical record (EMR) to capture high frequency interventions not standardly captured via existing standard note documentation (e.g., renal/hepatic dose adjustment, parenteral nutrition management). Value added of the interventions is proposed. Patients' baseline demographics, interventions, Sequential Organ Failure Assessment (SOFA) score, and intensive care unit (ICU) length of stay (LOS) were collected. The primary outcome was to determine the added benefit of using a tracking tool within the EMR to capture pharmacist interventions compared to progress note documentation. Results: Two thousand seven hundred and eighty‐three interventions were documented on 514 unique patients over 120 pharmacist shifts. Of these, 2363 (84.9%) interventions were captured through iVent tracking. The median SOFA score on day of intervention was 4 [interquartile range (IQR) 2–7] and ICU LOS was 3.5 days [IQR 1.5–9]. The median number of interventions per patient per day was 2 [IQR 1–3]. A significant difference was observed among days of the week and the number of iVents documented (χ2 = 13.172, p = 0.01, df = 4). The post hoc pairwise comparison revealed more documented iVents on Tuesday than Friday. Conclusion: This study reveals that an iVent tracking tool increased total capture of pharmacist interventions by 563%. These interventions can be associated with value‐based programs and further work is needed in highlighting the pharmacist's role in these new payment models. This study confirms that the current standard practice at this institution of solely entering pharmacist progress notes into the patient chart misses a majority of pharmacist interventions. [ABSTRACT FROM AUTHOR]

Local financial institutions can play a crucial role in reducing income inequalities at the within‐country level by promoting inclusive economic growth and development across time and space. This is against a backdrop of increasing financial and economic fragility, to which emerging economies have also been exposed over more recent decades and years. This article adds emerging economy evidence from Brazil to an empirical literature on the income inequality implications of cooperative financial institutions. Panel‐data estimations for 2004‒19 reveal that Brazilian credit cooperatives have gone beyond commercial banks in supporting communities that have traditionally been underserved financially. Additionally, the article provides new evidence and insights on credit cooperatives' resilience in the context of a relatively recent but severe economic crisis in Brazil. The results indicate that credit cooperatives have helped fill gaps in finance and economic opportunity that tend to arise in an emerging economy setting. Furthermore, the contribution of credit cooperatives in filling these gaps is found to be more significant at lower levels of development. These findings add theoretical and, importantly, empirical support to the relationship channel of financial inclusion, which is in line with the optimistic perspective in this debate. [ABSTRACT FROM AUTHOR]

Background: Bupivacaine lioposomal suspension has recently emerged in the veterinary field for local analgesia. Objective: To describe the extra‐label administration of bupivacaine liposomal suspension at the incision site of dogs undergoing limb amputation and characterize any complications. Study Design: Nonblinded retrospective study. Animals: Client‐owned dogs undergoing limb amputation from 2016 to 2020. Methods: Medical records of dogs undergoing limb amputation with concurrent use of long‐acting liposomal bupivacaine suspension were reviewed for incisional complications, adverse effects, hospitalization length, and time to alimentation. Data were compared to a control group (CG) of dogs who underwent a limb amputation procedure without concurrent use of liposomal bupivacaine suspension. Results: Forty‐six dogs were included in the liposomal bupivacaine group (LBG) and 44 cases in the CG. The CG had 15 incidences of incisional complications (34%) compared to 6 within the LBG (13%). Four dogs required revisional surgery in the CG (9%) whereas none of the dogs required revisional surgery in the LBG. Time from surgery to discharge was statistically higher in the CG compared to the LBG (p = 0.025). First time to alimentation was statistically higher in the CG (p value = 0.0002). The total number of rechecks needed postoperatively revealed the CG having a statistically significant increase in recheck evaluations (p = 0.001). Conclusions: Extra‐label administration of liposomal bupivacaine suspension was well‐tolerated in dogs undergoing limb amputation. Liposomal bupivacaine usage did not increase incisional complication rates and its use allowed for a quicker time to discharge. Clinical significance: Surgeons should consider inclusion of extra‐label administration of liposomal bupivacaine in analgesic regimens for dogs undergoing limb amputation. [ABSTRACT FROM AUTHOR]

Introduction: Expression of human complement pathway regulatory proteins (hCPRP's) such as CD46 or CD55 has been associated with improved survival of pig organ xenografts in multiple different models. Here we evaluate the hypothesis that an increased human CD46 gene dose, through homozygosity or additional expression of a second hCPRP, is associated with increased protein expression and with improved protection from injury when GTKO lung xenografts are perfused with human blood. Methods: Twenty three GTKO lungs heterozygous for human CD46 (GTKO.heteroCD46), 10 lungs homozygous for hCD46 (GTKO.homoCD46), and six GTKO.homoCD46 lungs also heterozygous for hCD55 (GTKO.homoCD46.hCD55) were perfused with human blood for up to 4 h in an ex vivo circuit. Results: Relative to GTKO.heteroCD46 (152 min, range 5–240; 6/23 surviving at 4 h), survival was significantly improved for GTKO.homoCD46 (>240 min, range 45–240, p =.034; 7/10 surviving at 4 h) or GTKO.homoCD46.hCD55 lungs (>240 min, p =.001; 6/6 surviving at 4 h). Homozygosity was associated with increased capillary expression of hCD46 (p <.0001). Increased hCD46 expression was associated with significantly prolonged lung survival (p =.048),) but surprisingly not with reduction in measured complement factor C3a. Hematocrit, monocyte count, and pulmonary vascular resistance were not significantly altered in association with increased hCD46 gene dose or protein expression. Conclusion: Genetic engineering approaches designed to augment hCPRP activity — increasing the expression of hCD46 through homozygosity or co‐expressing hCD55 with hCD46 — were associated with prolonged GTKO lung xenograft survival. Increased expression of hCD46 was associated with reduced coagulation cascade activation, but did not further reduce complement activation relative to lungs with relatively low CD46 expression. We conclude that coagulation pathway dysregulation contributes to injury in GTKO pig lung xenografts perfused with human blood, and that the survival advantage for lungs with increased hCPRP expression is likely attributable to improved endothelial thromboregulation. [ABSTRACT FROM AUTHOR]

Continuing professional development is a lifelong process that is multifaceted, holistic, self‐directed, and is not a replacement for continuing education. Through ongoing professional development, pharmacists can improve their skill set in a broad range of clinical, educational, research, and administrative activities. Not only does development of this growth benefit the individual pharmacist, but also the institution and pharmacy profession. In 2020, the American College of Clinical Pharmacy, the Society of Critical Care Medicine, and the American Society of Health‐System Pharmacists published an updated position paper on critical care pharmacy services. A new recommendation in the update was to create mechanisms for critical care pharmacists to develop their career and professional development. Herein, we describe our experience with the development and implementation of a critical care pharmacy career professional development program using peer‐to‐peer coaching within a large academic medical center. Professional development is not a one size fits all and should be individualized. We initially focused on developing research skills based on initial surveys. Afterwards professional development was varied we created new resources such as journal referee "how‐to" and teaching in a flipped classroom. [ABSTRACT FROM AUTHOR]

Background: Transfusion‐associated circulatory overload (TACO) is a severe adverse reaction (AR) contributing to the leading cause of mortality associated with transfusions. As strategies to mitigate TACO have been increasingly adopted, an update of prevalence rates and risk factors associated with TACO using the growing sources of electronic health record (EHR) data can help understand transfusion safety. Study Design and Methods: This retrospective study aimed to provide a timely and reproducible assessment of prevalence rates and risk factors associated with TACO. Novel natural language processing methods, now made publicly available on GitHub, were developed to extract ARs from 3178 transfusion reaction reports. Other patient‐level data were extracted computationally from UCSF EHR between 2012 and 2022. The odds ratio estimates of risk factors were calculated using a multivariate logistic regression analysis with case‐to‐control matched on sex and age at a ratio of 1:5. Results: A total of 56,208 patients received transfusions (total 573,533 units) at UCSF during the study period and 102 patients developed TACO. The prevalence of TACO was estimated to be 0.2% per patient (102/total 56,208). Patients with a history of coagulopathy (OR, 1.36; 95% CI, 1.04–1.79) and transplant (OR, 1.99; 95% CI, 1.48–2.68) were associated with increased odds of TACO. Discussion: While TACO is a serious AR, events remained rare, even in populations enriched with high‐risk patients. Novel computational methods can be used to find and continually surveil for transfusion ARs. Results suggest that patients with history or presence of coagulopathy and organ transplant should be carefully monitored to mitigate potential risks of TACO. [ABSTRACT FROM AUTHOR]

Cyprinid herpesvirus‐3 (CyHV‐3) is an important pathogen of common carp (Cyprinus carpio, carp) causing significant economic and ecological impacts worldwide. The recent emergence of CyHV‐3 in the Upper Midwest region of the United States has raised questions related to the disease ecology and host specificity of CyHV‐3 in wild carp populations. To determine the prevalence of CyHV‐3 in wild populations of fishes in Minnesota, we surveyed five lakes in 2019 in which the virus was known to have caused mass mortality events in carp from 2017 to 2018. A total of 28 species (n = 756 total fish) of native fishes and 730 carp were screened for the presence of CyHV‐3 DNA using specific qPCR. None of the native fish tissues tested positive for CyHV‐3 although the prevalence of CyHV‐3 in carp was 10%–50% in the five lakes. A single lake (Lake Elysian) with a 50% DNA detection rate and evidence of ongoing transmission and CyHV‐3‐associated mortality was surveyed again in 2020 from April to September. During this period, none of the tissues from 24 species (n = 607 total fish) tested positive for CyHV‐3 though CyHV‐3 DNA and mRNA (indicating viral replication) was detected in carp tissues during the sampling period. CyHV‐3 DNA was detected most often in brain samples without evidence of replication, potentially indicating that brain tissue is a site for CyHV‐3 latency. Paired qPCR and ELISA testing for Lake Elysian in 2019–2020 identified young carp (especially males) to be the primary group impacted by CyHV‐3‐associated mortality and acute infections, but with no positive detections in juvenile carp. Seroprevalence of carp from Lake Elysian was 57% in 2019, 92% in April of 2020 and 97% in September 2020. These results further corroborate the host specificity of CyHV‐3 to carp in mixed wild populations of fishes in Minnesota and provide additional insights into the ecological niche of CyHV‐3 in shallow lake populations of carp in North America. [ABSTRACT FROM AUTHOR]

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The role of the school nurse should not be understated when addressing the Covid‐19 pandemic and its effects on children and families. Knowledge surrounding this virus is rapidly changing and quick adaptation within the school system is required. In addition to the provision of direct care and education to students, school nurse responsibilities include the development and implementation of new policies; consideration of social and emotional well‐being; and effective communication with students, families, teachers, administrators, and community stakeholders. This article addresses current evidence related to the coronavirus disease 2019 (COVID‐19) pandemic and the evolving role of the school nurse. A case study incorporates tips and suggestions for school nurses who will deliver professional care during this COVID‐19 crisis. [ABSTRACT FROM AUTHOR]

Background: The US Pediatric Heart Allocation Policy (PHAP) was revised in March 2016, with the goal of reducing waitlist mortality. We evaluated the hypothesis that these changes, which increased status exceptions, have worsened racial disparities in waitlist outcomes. Methods: Children in the Pediatric Heart Transplant Study database listed for first heart transplant from January 2012 – June 2020 were included and stratified by listing before (Era 1) or after (Era 2) the PHAP revision. Results: A total of 4,089 children were listed during the study period. Compared with white children (n = 2648), non‐white children (n = 1441) were more likely to have an underlying diagnosis of cardiomyopathy in both eras. Waitlist mortality was similar in white and non‐white children in Era 1, but comparatively worse for non‐white children in Era 2. In multivariable analysis controlling for diagnosis, age, and severity markers, non‐white children had a significantly higher waitlist mortality only in Era 2 (Era 1: sHR 1.22 [95%CI 0.90 – 1.66] vs. Era 2: sHR 1.57 [95%CI 1.17 – 2.10]). Conclusions: Widening racial disparities in waitlist mortality may be an unintended consequence of the 2016 PHAP revision. Additional analyses may inform the degree to which this policy vs. unrelated changes in care differentially contribute to these disparities. [ABSTRACT FROM AUTHOR]

Salmonid fishes have emerged as a tractable model to study whole‐genome duplications (WGDs) as this group has undergone four rounds of WGDs. While most of the salmonid genome has returned to a diploid state, a significant proportion of genes are maintained as duplicates and are referred to as ohnologs. The fact that much of the modern salmonid gene repertoire is comprised of ohnologs, while other genes have returned to their singleton state creates complications for genetic studies by obscuring homology relationships. The difficulty this creates is particularly prominent in Pacific salmonids belonging to genus Oncorhynchus who are the focus of intense genetics‐based conservation and management efforts owing to the important ecological and cultural roles these fish play. To address this gap, we generated a homology guide for six species of Oncorhynchus with available genomes and used this guide to describe patterns of ohnolog retention and resolution. Overall, we find that ohnologs comprise approximately half of each species modern gene repertoires, which are functionally enriched for genes involved in DNA binding, while the less numerous singleton genes are heavily enriched in dosage‐sensitive processes such as mitochondrial metabolism. Additionally, by reanalyzing published expression data from locally adapted strains of O. mykiss, we show that numerous ohnologs exhibit adaptive expression profiles; however, ohnologs are not more likely to display adaptive signatures than either paralogs or singletons. Finally, we demonstrate the utility of our homology guide by investigating the evolutionary relationship among genes highlighted as playing a role in salmonid life‐history traits or gene editing targets. [ABSTRACT FROM AUTHOR]

Understanding survival probabilities is critical for the sustainable harvest of wildlife and fisheries populations. Age‐ and stage class‐specific survival probabilities are needed to inform a suite of population models used to estimate abundance and track population trends. However, current techniques for estimating survival probabilities using age‐at‐harvest methods require restrictive assumptions or incorporate potentially unknown parameters within the model.Using a Bayesian approach, we developed a flexible age‐at‐harvest model that incorporates either age‐ or stage‐structured populations, while accounting for uncertainty in age structure, population growth rates and relative selectivity. Survival probabilities can vary by age or stage class, as well as by environmental covariates, and both population growth rates and selectivity for each age or stage class can be specified as fixed and known or these parameters can be specified as informative priors, allowing for the incorporation of expert opinion. We evaluated our model with simulations and empirical data from harvested bobcats Lynx rufus and American paddlefish Polyodon spathula.Models fit to simulated age‐at‐harvest data yielded unbiased estimates of survival probability when population growth rates and selectivity were centered on the data‐generating parameter. We obtained unbiased estimates of survival probability even with biased prior estimates of selectivity and random departures from the assumed stage distribution, although the latter increased uncertainty in those estimates. We found biased estimates of survival probability when the prior distribution for population growth rate was not centered on the data‐generating value. When fit to empirical harvest data, our proposed age‐at‐harvest model produced estimates of survival probability congruent to those reported in the literature within similar geographic regions.We demonstrate the utility of a novel age‐at‐harvest model that estimates survival probability and realistically account for uncertainty in model parameters, transcending the restrictive assumptions and auxiliary data requirements of other methods. Furthermore, we advise collecting information about population trends and age structure alongside age‐at‐harvest data to help reduce bias. Although our model cannot replace more rigorous methods, we believe our model will be transformative for wildlife and fisheries practitioners who collect age‐at‐harvest data to estimate age‐ or stage‐specific survival probabilities to help inform management decisions. [ABSTRACT FROM AUTHOR]

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy has shown to improve survival in patients with extensive or refractory abdominal tumors of many different histologies. Postoperative pain control can be challenging as the surgical procedure is performed through a midline laparotomy incision from xiphoid to symphysis pubis, and patients are usually nothing by mouth for the first 8–10 postoperative days. Aims: We present the anesthetic management and postoperative pain control strategies for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy using a multimodal, opioid‐sparing, and total intravenous anesthetic technique with a tunneled thoracic epidural. Methods: A single institution retrospective review of anesthetic management, intraoperative fluid and blood administration, and postoperative pain control for pediatric patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy between July 2018 and December 2020 was conducted. We employed a novel anesthetic and analgesia protocol consisting of premedication with gabapentin followed by intraoperative infusions of propofol, dexmedetomidine, ketamine, and cisatracurium. A tunneled thoracic epidural catheter was placed for management of pain. Results: We reviewed and analyzed the first 25 patient records. The most common diagnosis was desmoplastic small round cell tumor (n = 12). Median age of patients was 14 years (range 21 months‐22 years). All patients were extubated in the operating room and no patients required reintubation. There were no incidences of acute kidney injury. Epidural infusions were used for a median of 8 days (range 2–14 days). Median postoperative intravenous opioid use (morphine equivalent) through postoperative day 10 was 0.02 mg/kg/day (range 0–0.86 mg/kg/day) administered for a median of 2 days (range 0–17 days). Nine patients (36%) did not require any intravenous opioids in the postoperative period. Conclusions: Utilizing a multimodal, opioid‐sparing, total intravenous anesthetic technique in conjunction with a tunneled thoracic epidural catheter, we were able to avoid the need for postoperative mechanical ventilation and minimize both intraoperative and postoperative opioid requirements. [ABSTRACT FROM AUTHOR]

We conducted a content analysis of generic qualitative counseling dissertations (GQR; N = 70), examining their methodological justifications, coherence, and trustworthiness. Dissertations authors often presented vague methodological justifications. Findings have implications for constructing methodological justifications, integrating relevant literature, and awareness of how GQR compares to other qualitative methodologies. [ABSTRACT FROM AUTHOR]

I formulate expected‐utility‐maximizing models for health insurance with a single optimal coinsurance (C*) and (separately) a single optimal deductible (D*). While so‐doing, I formalize Nyman's challenge to standard welfare‐loss models, clarifying when and by how much this alters unadjusted models. Using MEPS‐calibrated lognormal distributions and incorporating skewness and kurtosis measures of financial risk, I show how C* shifts as various economic parameters change. For reasonable parameter values, C* < 0.1, much lower than variance‐only estimates would conclude. Omitting higher‐order risk parameters importantly understates risk and hence understates optimal insurance coverage. I separately develop methods to determine D*, showing that it is approximately a fixed percentage of income that falls as the distribution of financial risks rise. This finding contrasts with existing US public policy regarding high‐deductible health plans, which employ fixed deductibles, independent of income. [ABSTRACT FROM AUTHOR]

Background: Guidelines‐driven screening protocols for early cancer detection in dogs are lacking, and cancer often is detected at advanced stages. Hypothesis/Objectives: To examine how cancer typically is detected in dogs and whether the addition of a next‐generation sequencing‐based "liquid biopsy" test to a wellness visit has the potential to enhance cancer detection. Animals: Client‐owned dogs with definitive cancer diagnoses enrolled in a clinical validation study for a novel blood‐based multicancer early detection test. Methods: Retrospective medical record review was performed to establish the history and presenting complaint that ultimately led to a definitive cancer diagnosis. Blood samples were subjected to DNA extraction, library preparation, and next‐generation sequencing. Sequencing data were analyzed using an internally developed bioinformatics pipeline to detect genomic alterations associated with the presence of cancer. Results: In an unselected cohort of 359 cancer‐diagnosed dogs, 4% of cases were detected during a wellness visit, 8% were detected incidentally, and 88% were detected after the owner reported clinical signs suggestive of cancer. Liquid biopsy detected disease in 54.7% (95% confidence interval [CI], 49.5%‐59.8%) of patients, including 32% of dogs with early‐stage cancer, 48% of preclinical dogs, and 84% of dogs with advanced‐stage disease. Conclusions/Clinical Importance: Most cases of cancer were diagnosed after the onset of clinical signs; only 4% of dogs had cancer detected using the current standard of care (i.e., wellness visit). Liquid biopsy has the potential to increase detection of cancer when added to a dog's wellness visit. [ABSTRACT FROM AUTHOR]

Previous research has shown that the home ownership status of parents matters for the likelihood of a child becoming an owner, and other research has studied how financial intergenerational transfers affect the transition to ownership. We extend these existing studies by estimating the effect of financial transfers on the probability of becoming an owner as well as the role of in‐kind transfers. We also analyse how the impacts of different intergenerational transmission channels vary across neighbourhoods of advantage and disadvantage and discuss the implications for inequality in access to ownership. Drawing on a large panel data set from the Household, Income and Labour Dynamics in Australia Survey, we offer three new findings. First, we show that financial transfers made concurrently with home purchases play a more important role than lagged transfers and that in‐kind transfers are also an important part of the process of gaining ownership. Second, we note that in‐kind transfers are more effective for raising home ownership prospects in areas with high socioeconomic status, while financial transfers appear to be more effective in middle‐class neighbourhoods. Third, children from disadvantaged backgrounds are least likely to be assisted into home ownership by intergenerational transfers. [ABSTRACT FROM AUTHOR]

Narratives of landscape degradation are often linked to unsustainable fire use by local communities. Madagascar is a case in point: the island is considered globally exceptional, with its remarkable endemic biodiversity viewed as threatened by unsustainable anthropogenic fire. Yet, fire regimes on Madagascar have not been empirically characterised or globally contextualised. Here, we contribute a comparative approach to determining relationships between regional fire regimes and global patterns and trends, applied to Madagascar using MODIS remote sensing data (2003–2019). Rather than a global exception, we show that Madagascar's fire regimes are similar to 88% of tropical burned area with shared climate and vegetation characteristics, and can be considered a microcosm of most tropical fire regimes. From 2003–2019, landscape‐scale fire declined across tropical grassy biomes (17%–44% excluding Madagascar), and on Madagascar at a relatively fast rate (36%–46%). Thus, high tree loss anomalies on the island (1.25–4.77× the tropical average) were not explained by any general expansion of landscape‐scale fire in grassy biomes. Rather, tree loss anomalies centred in forests, and could not be explained by landscape‐scale fire escaping from savannas into forests. Unexpectedly, the highest tree loss anomalies on Madagascar (4.77×) occurred in environments without landscape‐scale fire, where the role of small‐scale fires (<21 h [0.21 km2]) is unknown. While landscape‐scale fire declined across tropical grassy biomes, trends in tropical forests reflected important differences among regions, indicating a need to better understand regional variation in the anthropogenic drivers of forest loss and fire risk. Our new understanding of Madagascar's fire regimes offers two lessons with global implications: first, landscape‐scale fire is declining across tropical grassy biomes and does not explain high tree loss anomalies on Madagascar. Second, landscape‐scale fire is not uniformly associated with tropical forest loss, indicating a need for socio‐ecological context in framing new narratives of fire and ecosystem degradation. [ABSTRACT FROM AUTHOR]

Recent increases of animal mass mortality events have coincided with substantial changes in global climate. Yet, tractable approaches that predict how climate change will accentuate occurrences of these ecological catastrophes remain nascent. We compiled one of the most comprehensive datasets of lentic fish mortality events, thermal tolerances of affected families, and 1.2 million air and water temperature profiles across 8891 north temperate lakes in North America. Temperature extremes within and across lakes were strongly associated with the three most frequent cause types (infectious agents, summerkills, winterkills). Thermal tolerances mediated the lethality of direct thermal stress, but mortalities of warm‐ and cold‐water fishes occurred at similar temperature deviations. Water and air temperature‐based models accurately predicted contemporary summerkills and suggested ~ 6‐ to 34‐fold increases, respectively, in their frequency by 2100. These models forecast and contextualize impending ecosystem changes in an increasingly volatile world. [ABSTRACT FROM AUTHOR]

The use of mechanical circulatory support (MCS) for pediatric patients who have undergone heart transplant has grown rapidly in the past decade. This includes support in the immediate post‐transplant period and "rescue" therapy for patient later in their transplant course. Extracorporeal membrane oxygenation (ECMO) remains a standard modality of support for intraoperative concerns and for acute decompensation in the immediate post‐transplant period. However, both pulsatile and continuous flow ventricular assist devices (VADs) have been used with increasing success in transplant patients for longer durations of support. Centers participating in the Pediatric Heart Transplant Society (PHTS) were queried to provide their internal protocols and rationale for mechanical circulatory support following heart transplant. These protocols coupled with evidence‐based literature were used to provide the following description of clinical approaches to MCS in the transplant patient highlighting areas of both broad consensus and significant practice variation. [ABSTRACT FROM AUTHOR]

Plain language summary: Biomarkers may offer unforeseen insights into clinical diagnosis, as well as the likely course and outcome of a condition. In this paper, the focus is on the use of biological molecules found in body fluids or tissues for diagnosis and prediction of outcome in ovarian cancer patients. In cancer care, biomarkers are being used to develop personalised treatment plans for patients based on the unique characteristics of their tumour. This tailoring of care can be used to pursue specific targets identified by biomarkers, or treat the patient according to specific tumour characteristics. Surgery is one of the core treatments for ovarian cancer, whether it is offered in primary surgery or following chemotherapy in delayed surgery. Biomarkers already exist to guide the treatment of tumours with chemotherapy, but very little research has determined the value of biomarkers in tailoring surgical care for ovarian cancer. Such research is required to identify new biomarkers and assess their effectiveness in a clinical setting as well as to help identify specific tumour types to guide surgery. Biomarkers could help to determine the success of removing the disease surgically, or help to identify tumour deposits that persist after chemotherapy. All of these aspects would improve current practice. This Scientific Impact Paper highlights research that may pave the way towards bespoke surgery according to the biological characteristics of a tumour and aid gynaecological oncologists to provide surgical treatment according to individual need, rather than a blanket approach for all. [ABSTRACT FROM AUTHOR]

Uveal melanoma (UM) is the most common primary malignancy of the adult eye but lacks any FDA‐approved therapy for the deadly metastatic disease. Thus, there is a great need to dissect the driving mechanisms for UM and develop strategies to evaluate potential therapeutics. Using an autochthonous zebrafish model, we previously identified MITF, the master melanocyte transcription factor, as a tumor suppressor in GNAQQ209L‐driven UM. Here, we show that zebrafish mitfa‐deficient GNAQQ209L‐driven tumors significantly up‐regulate neural crest markers, and that higher expression of a melanoma‐associated neural crest signature correlates with poor UM patient survival. We further determined how the mitfa‐null state, as well as expression of GNAQQ209L, YAPS127A;S381A, or BRAFV600E oncogenes, impacts melanocyte lineage cells before they acquire the transformed state. Specifically, examination 5 days post‐fertilization showed that mitfa‐deficiency is sufficient to up‐regulate pigment progenitor and neural crest markers, while GNAQQ209L expression promotes a proliferative phenotype that is further enhanced by YAPS127A;S381A co‐expression. Finally, we show that this oncogene‐induced proliferative phenotype can be used to screen chemical inhibitors for their efficacy against the UM pathway. Overall, this study establishes that a neural crest signature correlates with poor UM survival, and describes an in vivo assay for preclinical trials of potential UM therapeutics. [ABSTRACT FROM AUTHOR]

The use of areca nuts (areca) in the form of betel quids constitutes the fourth most common addiction in the world, associated with high risk for oral disease and cancer. Areca is a complex natural product, making it difficult to identify specific components associated with the addictive and carcinogenic properties. It is commonly believed that the muscarinic agonist arecoline is at the core of the addiction. However, muscarinic receptor activation is not generally believed to support drug-taking behaviour. Subjective accounts of areca use include descriptions of both sedative and stimulatory effects, consistent with the presence of multiple psychoactive agents. We have previously reported partial agonism of α4-containing nicotinic acetylcholine receptors by arecoline and subsequent inhibition of those receptors by whole areca broth. In the present study, we report the inhibition of nicotinic acetylcholine receptors and other types of neurotransmitter receptors with compounds of high molecular weight in areca and the ability of low molecular weight areca extract to activate GABA and glutamate receptors. We confirm the presence of a high concentration of GABA and glutamate in areca. Additionally, data also indicate the presence of a dopamine and serotonin transporter blocking activity in areca that could account for the reported stimulant and antidepressant activity. Our data suggest that toxic elements of high molecular weight may contribute to the oral health liability of betel quid use, while two distinct low molecular weight components may provide elements of reward, and the nicotinic activity of arecoline contributes to the physical dependence of addiction. [ABSTRACT FROM AUTHOR]

Bat species commonly comprise at least 50% of tropical mammalian assemblages, but Afrotropical bat faunas have been little studied leading to perceptions that they are depauperate. Here, we compare alpha taxonomic, functional, and phylogenetic diversity of insectivorous bats belonging to the narrow‐space foraging ensemble from a bat diversity hotspot in Nigeria to species‐rich sites in Indonesia and Malaysia, using previously published data. The Nigerian site is protected unlogged forests at Afi Mountain Wildlife Sanctuary and Cross River National Park. For comparison, we targeted similar unlogged forest sites in Southeast Asia: Indonesia—Bukit Barisan Selatan National Park Forest in Sumatra; and Kakenauwe Forest Reserve on Buton Island, Sulawesi; and another in Malaysia—Krau Wildlife Reserve. All sites were sampled using comparable methods, with an emphasis on harp traps that effectively capture the forest‐interior ensembles. We also compare regional beta diversity of bat assemblages in ecoregions using occurrence data (literature, unpublished records, and online natural history collections) from the Lower Guinean Forest and the Malay Peninsula. We demonstrate comparable alpha taxonomic, functional, and phylogenetic diversity of narrow‐space bats among sites in Nigeria and Indonesia, but greater diversity in Malaysia. Turnover and overall beta diversity of bats among ecoregions was comparable between the Lower Guinean Forest and the Malay Peninsula, but nestedness was higher in the latter. Our results reiterate the value of harp traps in generating bat survey data that allows equatable comparisons of "mist net avoiders" in the Paleotropical forest understory. Our findings have implications for regional and local bat conservation. [ABSTRACT FROM AUTHOR]

Vocalizations are often elaborate, rhythmically structured behaviors. Vocal motor patterns require close coordination of neural circuits governing the muscles of the larynx, jaw, and respiratory system. In the elaborate vocalization of Alston's singing mouse (Scotinomys teguina) each note of its rapid, frequency‐modulated trill is accompanied by equally rapid modulation of breath and gape. To elucidate the neural circuitry underlying this behavior, we introduced the polysynaptic retrograde neuronal tracer pseudorabies virus (PRV) into the cricothyroid and digastricus muscles, which control frequency modulation and jaw opening, respectively. Each virus singly labels ipsilateral motoneurons (nucleus ambiguus for cricothyroid, and motor trigeminal nucleus for digastricus). We find that the two isogenic viruses heavily and bilaterally colabel neurons in the gigantocellular reticular formation, a putative central pattern generator. The viruses also show strong colabeling in compartments of the midbrain including the ventrolateral periaqueductal gray and the parabrachial nucleus, two structures strongly implicated in vocalizations. In the forebrain, regions important to social cognition and energy balance both exhibit extensive colabeling. This includes the paraventricular and arcuate nuclei of the hypothalamus, the lateral hypothalamus, preoptic area, extended amygdala, central amygdala, and the bed nucleus of the stria terminalis. Finally, we find doubly labeled neurons in M1 motor cortex previously described as laryngeal, as well as in the prelimbic cortex, which indicate these cortical regions play a role in vocal production. The progress of both viruses is broadly consistent with vertebrate‐general patterns of vocal circuitry, as well as with circuit models derived from primate literature. [ABSTRACT FROM AUTHOR]