Quantitative support for the benefits of proactive management for wildlife disease control.

Finding effective pathogen mitigation strategies is one of the biggest challenges humans face today. In the context of wildlife, emerging infectious diseases have repeatedly caused widespread host morbidity and population declines of numerous taxa. In areas yet unaffected by a pathogen, a proactive management approach has the potential to minimize or prevent host mortality. However, typically critical information on disease dynamics in a novel host system is lacking, empirical evidence on efficacy of management interventions is limited, and there is a lack of validated predictive models. As such, quantitative support for identifying effective management interventions is largely absent, and the opportunity for proactive management is often missed. We considered the potential invasion of the chytrid fungus, Batrachochytrium salamandrivorans (Bsal), whose expected emergence in North America poses a severe threat to hundreds of salamander species in this global salamander biodiversity hotspot. We developed and parameterized a dynamic multistate occupancy model to forecast host and pathogen occurrence, following expected emergence of the pathogen, and evaluated the response of salamander populations to different management scenarios. Our model forecasted that taking no action is expected to be catastrophic to salamander populations. Proactive action was predicted to maximize host occupancy outcomes relative to wait-and-see reactive management, thus providing quantitative support for proactive management opportunities. The eradication of Bsal was unlikely under all the evaluated management options. Contrary to our expectations, even early pathogen detection had little effect on Bsal or host occupancy outcomes. Our results provide quantitative support that proactive management is the optimal strategy for promoting persistence of disease-threatened salamander populations. Our approach fills a critical gap by defining a framework for evaluating management options prior to pathogen invasion and can thus serve as a template for addressing novel disease threats that jeopardize wildlife and human health.

Apoyo cuantitativo para los beneficios de la gestión proactiva del control de enfermedades silvestres Resumen Uno de los mayores retos en la actualidad es encontrar estrategias eficaces de mitigación de patógenos. En el contexto de la fauna silvestre, las enfermedades infecciosas emergentes han causado en varias ocasiones una morbilidad generalizada de los hospedadores y el declive de las poblaciones de numerosos taxones. En zonas aún no afectadas por un patógeno, un enfoque de gestión proactivo tiene el potencial de minimizar o prevenir la mortalidad de los hospederos. Sin embargo, en general se carece de información crítica sobre la dinámica de la enfermedad en el nuevo sistema huésped, las pruebas empíricas sobre la eficacia de las intervenciones de gestión son limitadas y faltan modelos predictivos validados. Por lo tanto, no existe un apoyo cuantitativo para identificar intervenciones de gestión eficaces y a menudo se pierde la oportunidad de una gestión proactiva. Consideramos la posible invasión del hongo quitridio Batrachochytrium salamandrivorans (Bsal), cuya aparición prevista en América del Norte supone una grave amenaza para cientos de especies de salamandras en este punto caliente de la biodiversidad mundial de salamandras. Desarrollamos y parametrizamos un modelo dinámico de ocupación multiestado para predecir la presencia de hospederos y patógenos, tras la aparición esperada del patógeno, y evaluamos la respuesta de las poblaciones de salamandras a diferentes escenarios de gestión. Nuestro modelo predijo que no tomar ninguna medida sería catastrófico para las poblaciones de salamandras. También predijo que la acción proactiva maximizaría los resultados de ocupación de hospederos en relación con la gestión reactiva de esperar y ver, proporcionando así un apoyo cuantitativo a las oportunidades de gestión proactiva. La erradicación de Bsal fue improbable bajo todas las opciones de gestión evaluadas. Contrariamente a nuestras expectativas, incluso la detección temprana del patógeno tuvo poco efecto sobre los resultados de ocupación de Bsal o del hospedador. Nuestros resultados apoyan cuantitativamente a la gestión proactiva como la estrategia óptima para promover la persistencia de poblaciones de salamandras amenazadas por la enfermedad. Nuestro enfoque llena un vacío crítico al definir un marco para evaluar las opciones de gestión antes de la invasión de patógenos y, por lo tanto, puede servir como plantilla para hacer frente a nuevas amenazas de enfermedades que ponen en peligro la vida silvestre y la salud humana.

Comparative morphology in the context of facial reduction: Modularity in primate, dog, and bat crania.

Biological variation in the mammalian skull is the product of a series of factors including changes in gene expression, developmental timing, and environmental pressures. When considering the diversity of extant mammalian crania, it is important to understand these mechanisms that contribute to cranial growth and in turn, how differences in cranial morphology have been attained. Various researchers, including Dr. Sue Herring, have proposed a variety of mechanisms to explain the process of cranial growth. This work has set the foundation on which modern analysis of craniofacial morphology happens today. This study focused on the analysis of modularity in three mammalian taxa, all of which exhibit facial reduction. Specifically, we examined facial reduction as a morphological phenomenon through the use of two-module and six-module modularity hypotheses. We recorded three-dimensional coordinate data for 55 cranial landmarks that allowed us to analyze differences in cranial shape in these three taxa (primates n = 88, bats n = 64, dogs n = 81). When assessing modularity within the two-module modularity hypothesis specifically, dogs exhibited the lowest levels of modularity, while bats and primates both showed a slightly more modular covariance structure. We further assessed modularity in the same sample using the Goswami six-module model, where again dogs exhibited a low degree of modularity, with bats and primates being more moderate. We then broke the sample into subsets by analyzing each morphotype separately. We hypothesized that the modularity would be more pronounced in the brachycephalic morphotype. Surprisingly, we found that in brachycephalic dogs, normocephalic dogs, brachycephalic primates, and normocephalic primates, there was a moderate degree of modularity. Brachycephalic bats had a low degree of modularity, while normocephalic bats were the most modular group observed in this study. Based on these results, it is evident that facial reduction is a complex and multifaceted phenomenon with unique morphological changes observed in each of the three taxa studied.

Helicobacter pylori and Campylobacter jejuni bacterial holocytochrome c synthase structure-function analysis reveals conservation of heme binding.

Heme trafficking is essential for cellular function, yet mechanisms of transport and/or heme interaction are not well defined. The System I and System II bacterial cytochrome c biogenesis pathways are developing into model systems for heme trafficking due to their functions in heme transport, heme stereospecific positioning, and mediation of heme attachment to apocytochrome c. Here we focus on the System II pathway, CcsBA, that is proposed to be a bi-functional heme transporter and holocytochrome c synthase. An extensive structure-function analysis of recombinantly expressed Helicobacter pylori and Campylobacter jejuni CcsBAs revealed key residues required for heme interaction and holocytochrome c synthase activity. Homologous residues were previously identified to be required for heme interaction in Helicobacter hepaticus CcsBA. This study provides direct, biochemical evidence that mechanisms of heme interaction are conserved, leading to the proposal that the CcsBA WWD heme-handling domain represents a novel target for therapeutics.

Identification of Parkinson's disease PACE subtypes and repurposing treatments through integrative analyses of multimodal data.

Parkinson's disease (PD) is a serious neurodegenerative disorder marked by significant clinical and progression heterogeneity. This study aimed at addressing heterogeneity of PD through integrative analysis of various data modalities. We analyzed clinical progression data (≥5 years) of individuals with de novo PD using machine learning and deep learning, to characterize individuals' phenotypic progression trajectories for PD subtyping. We discovered three pace subtypes of PD exhibiting distinct progression patterns: the Inching Pace subtype (PD-I) with mild baseline severity and mild progression speed; the Moderate Pace subtype (PD-M) with mild baseline severity but advancing at a moderate progression rate; and the Rapid Pace subtype (PD-R) with the most rapid symptom progression rate. We found cerebrospinal fluid P-tau/α-synuclein ratio and atrophy in certain brain regions as potential markers of these subtypes. Analyses of genetic and transcriptomic profiles with network-based approaches identified molecular modules associated with each subtype. For instance, the PD-R-specific module suggested STAT3, FYN, BECN1, APOA1, NEDD4, and GATA2 as potential driver genes of PD-R. It also suggested neuroinflammation, oxidative stress, metabolism, PI3K/AKT, and angiogenesis pathways as potential drivers for rapid PD progression (i.e., PD-R). Moreover, we identified repurposable drug candidates by targeting these subtype-specific molecular modules using network-based approach and cell line drug-gene signature data. We further estimated their treatment effects using two large-scale real-world patient databases; the real-world evidence we gained highlighted the potential of metformin in ameliorating PD progression. In conclusion, this work helps better understand clinical and pathophysiological complexity of PD progression and accelerate precision medicine.

Recombinant Biogenesis and Analysis of Cytochrome c Species.

Recombinant expression and biogenesis of cytochrome c species is a simple and efficient method for the production of holocytochrome c species, thus presenting an avenue for the study of cytochrome c or the cytochrome c biogenesis pathways responsible for heme attachment. Here, we describe a method for recombinant E. coli production of holocytochrome c utilizing the System I (CcmABCDEFGH) bacterial cytochrome c biogenesis pathway, followed by analysis of cytochrome c species by cell lysis and heme stain.

Features of Consistent Powassan Virus Lineage II Focus in Southern Maine, United States.

Powassan virus lineage II or deer tick virus (DTV) is a rare but increasingly reported human infection in the United States transmitted by Ixodes scapularis ticks. The virus is thought to be maintained in environmental foci that are optimal for tick and vertebrate reservoirs, but details on DTV ecology are poorly understood. We investigated DTV tick infection rates and reservoir host abundance in a focus of consistent DTV activity in Maine, USA. Host and tick abundance, vegetation, and microclimate conditions were measured in three forest sites representing increasing invasive understory infestation. Sites were selected representing native understory, mixed vegetation with some invasive Japanese barberry (Berberis thunbergii), and a highly invasive site dominated by Japanese barberry. Japanese barberry in the mixed vegetation site averaged 1 m in height with space between plants, whereas the highly invasive site had impenetrable Japanese barberry over 1.5 m. The DTV infection rate was greater in the highly invasive site. Density of I. scapularis ticks were significantly lower in the native forest site, and no DTV was found. Another feature of the DTV focus was more stable humid microclimate throughout the year compared with the other sites and a nearby continuous section of forest, consistent with reports from Connecticut, USA. We conclude that invasive Japanese barberry stands provide favorable and consistent microclimate conditions to maintain high DTV infection rates annually among questing I. scapularis ticks. Understanding environmental and landscape features that support high infection rates could lead to the identification of high-risk habitats for contracting DTV.

Exploring perceptions of inpatient hospital attire in children with cancer.

BACKGROUND: Attire bolsters identity, self-expression, and comfort. Hospital gowns are known to be distressing in adults. Attitudes of children with cancer toward hospital attire remain uninvestigated and may be a modifiable factor in overall well-being. METHODS: A 39-item mixed methods survey evaluated perceptions of patient attire in children with cancer. Children aged 7-18 years were recruited at an academic medical center. Data analysis included simple statistics and thematic analysis. RESULTS: Forty children with cancer receiving oncologic care participated. Participants' mean age was 12.4 (SD = 3.0, range = 7-17) years, and 25 (62%) were male. Quantitative data revealed 81% of participants preferred their own attire when admitted to the hospital, feeling more comfortable in such when well (91%) or sick (75%). They did not feel like they "must" wear a gown when admitted (60%) and did not want to be asked about preferred inpatient attire (63%). Thematic analysis revealed that children had strong negative views of gowns and preferred to wear their own attire in the hospital, which provided physical and emotional comfort. Children worried wearing their own clothing could impede their care. CONCLUSION: Children with cancer prefer wearing their own clothes in the hospital for physical and emotional comfort. They are willing to wear gowns for ease of care; however, they do not want to arbitrate when they need to make that choice. Providers may ease distress by considering a child's own clothes as default hospital attire with instructions for when a gown is necessary for good clinical care.

Capture rates of Eptesicus fuscus increase following white-nose syndrome across the eastern US.

Emerging infectious diseases threaten wildlife globally. While the effects of infectious diseases on hosts with severe infections and high mortality rates often receive considerable attention, effects on hosts that persist despite infection are less frequently studied. To understand how persisting host populations change in the face of disease, we quantified changes to the capture rates of Eptesicus fuscus (big brown bats), a persisting species susceptible to infection by the invasive fungal pathogen Pseudogymnoascus destructans (Pd; causative agent for white-nose syndrome), across the eastern US using a 30-year dataset. Capture rates of male and female E. fuscus increased from preinvasion to pathogen establishment years, with greater increases to the capture rates of females than males. Among females, capture rates of pregnant and post-lactating females increased by pathogen establishment. We outline potential mechanisms for these broad demographic changes in E. fuscus capture rates (i.e., increases to foraging from energy deficits created by Pd infection, increases to relative abundance, or changes to reproductive cycles), and suggest future research for identifying mechanisms for increasing capture rates across the eastern US. These data highlight the importance of understanding how populations of persisting host species change following pathogen invasion across a broad spatial scale. Understanding changes to population composition following pathogen invasion can identify broad ecological patterns across space and time, and open new avenues for research to identify drivers of those patterns.

Organisms have gravity: taking an organism-centered approach in experimental biology.

When you take the time to observe another organism, there is a sort of gravity that can take hold, a mixture of curiosity and connection that expands and strengthens the more you interact with that organism. Yet, in research, a connection with one's study organism can, at times, feel countercultural. Study organisms are sometimes viewed more as tools to conveniently study biological questions. Here, we explicitly highlight the importance of organism-centered research not only in scientific discovery, but also in conservation and in the communication and perception of science.

At the onset of active whisking, the input layer of barrel cortex exhibits a 24 h window of increased excitability that depends on prior experience.

The development of motor control over sensory organs is a critical milestone in sensory processing, enabling active exploration and shaping of the sensory environment. However, whether the onset of sensory organ motor control directly influences the development of corresponding sensory cortices remains unknown. Here, we exploit the late onset of whisking behavior in mice to address this question in the somatosensory system. Using ex vivo electrophysiology, we discovered a transient increase in the intrinsic excitability of excitatory neurons in layer IV of the barrel cortex, which processes whisker input, precisely coinciding with the onset of active whisking at postnatal day 14 (P14). This increase in neuronal gain was specific to layer IV, independent of changes in synaptic strength, and required prior sensory experience. Strikingly, the effect was not observed in layer II/III of the barrel cortex or in the visual cortex upon eye opening, suggesting a unique interaction between the development of active sensing and the thalamocortical input layer in the somatosensory system. Predictive modeling indicated that changes in active membrane conductances alone could reliably distinguish P14 neurons in control but not whisker-deprived hemispheres. Our findings demonstrate an experience-dependent, lamina-specific refinement of neuronal excitability tightly linked to the emergence of active whisking. This transient increase in the gain of the thalamic input layer coincides with a critical period for synaptic plasticity in downstream layers, suggesting a role in facilitating cortical maturation and sensory processing. Together, our results provide evidence for a direct interaction between the development of motor control and sensory cortex, offering new insights into the experience-dependent development and refinement of sensory systems. These findings have broad implications for understanding the interplay between motor and sensory development, and how the mechanisms of perception cooperate with behavior.

Amphibians exhibit extremely high hydric costs of respiration.

Terrestrial environments pose many challenges to organisms, but perhaps one of the greatest is the need to breathe while maintaining water balance. Breathing air requires thin, moist respiratory surfaces, and thus the conditions necessary for gas exchange are also responsible for high rates of water loss that lead to desiccation. Across the diversity of terrestrial life, water loss acts as a universal cost of gas exchange and thus imposes limits on respiration. Amphibians are known for being vulnerable to rapid desiccation, in part because they rely on thin, permeable skin for cutaneous respiration. Yet we have a limited understanding of the relationship between water loss and gas exchange within and among amphibian species. In this study, we evaluated the hydric costs of respiration in amphibians using the transpiration ratio, which is defined as the ratio of water loss (mol H2O d-1) to gas uptake (mol O2 d-1). A high ratio suggests greater hydric costs relative to the amount of gas uptake. We compared the transpiration ratio of amphibians with that of other terrestrial organisms to determine if amphibians had greater hydric costs of gas uptake relative to plants, insects, birds, and mammals. We also evaluated the effects of temperature, humidity, and body mass on the transpiration ratio both within and among amphibian species. We found that hydric costs of respiration in amphibians were two to four orders of magnitude higher than the hydric costs of plants, insects, birds, and mammals. We also discovered that larger amphibians had lower hydric costs than smaller amphibians, at both the species- and individual-level. Amphibians also reduced the hydric costs of respiration at warm temperatures, potentially reflecting adaptive strategies to avoid dehydration while also meeting the demands of higher metabolic rates. Our results suggest that cutaneous respiration is an inefficient mode of respiration that produces the highest hydric costs of respiration yet to be measured in terrestrial plants and animals. Yet, amphibians largely avoid these costs by selecting aquatic or moist environments, which may facilitate more independent evolution of water loss and gas exchange.

Safety and effectiveness of transsplenic access for portal venous interventions: a single-center retrospective study.

PURPOSE: To assess the safety and effectiveness of percutaneous transsplenic access (PTSA) for portal vein (PV) interventions among patients with PV disease. MATERIALS AND METHODS: Adult patients with PV disease were enrolled if they required percutaneous catheterization for PV angioplasty, embolization, thrombectomy, variceal embolization, or transjugular intrahepatic portosystemic shunt (TIPS) placement for a difficult TIPS or recanalization of a chronically occluded PV. The procedures were performed between January 2018 and January 2023. Patients were excluded if they had an active infection, had a chronically occluded splenic vein malignant infiltration of the needle tract, had undergone splenectomy, or were under age 18 years. RESULTS: Thirty patients (15 women, 15 men) were enrolled. Catheterization of the PV through PTSA succeeded for 29 of 30 patients (96.7%). The main adverse effect recorded was flank pain in 5 of 30 cases (16.7%). No bleeding events from the spleen, splenic vein, or percutaneous access point were recorded. Two cases (6.7%) each of hepatic bleeding and rethrombosis of the PV were reported, and a change in hemoglobin levels (mean [SD], - 0.5 [1.4] g/dL) was documented in 14 cases (46.7%). CONCLUSION: PTSA as an approach to accessing the PV is secure and achievable, with minimal risk of complications. Minimal to no bleeding is possible by using tract closure methods.

Reframing wildlife disease management problems with decision analysis.

Contemporary wildlife disease management is complex because managers need to respond to a wide range of stakeholders, multiple uncertainties, and difficult trade-offs that characterize the interconnected challenges of today. Despite general acknowledgment of these complexities, managing wildlife disease tends to be framed as a scientific problem, in which the major challenge is lack of knowledge. The complex and multifactorial process of decision-making is collapsed into a scientific endeavor to reduce uncertainty. As a result, contemporary decision-making may be oversimplified, rely on simple heuristics, and fail to account for the broader legal, social, and economic context in which the decisions are made. Concurrently, scientific research on wildlife disease may be distant from this decision context, resulting in information that may not be directly relevant to the pertinent management questions. We propose reframing wildlife disease management challenges as decision problems and addressing them with decision analytical tools to divide the complex problems into more cognitively manageable elements. In particular, structured decision-making has the potential to improve the quality, rigor, and transparency of decisions about wildlife disease in a variety of systems. Examples of management of severe acute respiratory syndrome coronavirus 2, white-nose syndrome, avian influenza, and chytridiomycosis illustrate the most common impediments to decision-making, including competing objectives, risks, prediction uncertainty, and limited resources.

Replanteamiento del manejo de problemas por enfermedades de fauna mediante el análisis de decisiones Resumen El manejo actual de las enfermedades de la fauna es complejo debido a que los gestores necesitan responder a una amplia gama de actores, varias incertidumbres y compensaciones difíciles que caracterizan los retos interconectados del día de hoy. A pesar de que en general se reconocen estas complejidades, el manejo de las enfermedades tiende a plantearse como un problema científico en el que el principal obstáculo es la falta de conocimiento. El proceso complejo y multifactorial de la toma decisiones está colapsado dentro de un esfuerzo científico para reducir la incertidumbre. Como resultado de esto, las decisiones contemporáneas pueden estar simplificadas en exceso, depender de métodos heurísticos simples y no considerar el contexto legal, social y económico más amplio en el que se toman las decisiones. De manera paralela, las investigaciones científicas sobre las enfermedades de la fauna pueden estar lejos de este contexto de decisiones, lo que deriva en información que puede no ser directamente relevante para las preguntas pertinentes de manejo. Proponemos replantear los obstáculos para el manejo de enfermedades de fauna como problemas de decisión y abordarlos con herramientas analíticas de decisión para dividir los problemas complejos en elementos más manejables de manera cognitiva. En particular, las decisiones estructuradas tienen el potencial de mejorar la calidad, el rigor y la transparencia de las decisiones sobre las enfermedades de la fauna en una variedad de sistemas. Ejemplos como el manejo del coronavirus del síndrome de respiración agudo tipo 2, el síndrome de nariz blanca, la influenza aviar y la quitridiomicosis ilustran los impedimentos más comunes para la toma de decisiones, incluyendo los objetivos en competencia, riesgos, incertidumbre en las predicciones y recursos limitados.

An extinct north American porcupine with a South American tail.

New World porcupines (Erethizontinae) originated in South America and dispersed into North America as part of the Great American Biotic Interchange (GABI) 3-4 million years ago.1 Extant prehensile-tailed porcupines (Coendou) today live in tropical forests of Central and South America.2,3 In contrast, North American porcupines (Erethizon dorsatum) are thought to be ecologically adapted to higher-latitude temperate forests, with a larger body, shorter tail, and diet that includes bark.4,5,6,7 Limited fossils8,9,10,11,12,13 have hindered our understanding of the timing of this ecological differentiation relative to intercontinental dispersal during the GABI and expansion into temperate habitats.14,15,16,17,18 Here, we describe functionally important features of the skeleton of the extinct Erethizon poyeri, the oldest nearly complete porcupine skeleton documented from North America, found in the early Pleistocene of Florida. It differs from extant E. dorsatum in having a long, prehensile tail, grasping foot, and lacking dental specializations for bark gnawing, similar to tropical Coendou. Results from phylogenetic analysis suggest that the more arboreal characteristics found in E. poyeri are ancestral for erethizontines. Only after it expanded into temperate, Nearctic habitats did Erethizon acquire the characteristic features that it is known for today. When combined with molecular estimates of divergence times, results suggest that Erethizon was ecologically similar to a larger species of Coendou when it crossed the Isthmus of Panama by the early Pleistocene. It is likely that the range of this more tropically adapted form was limited to a continuous forested biome that extended from South America through the Gulf Coast.

Novel extended-release transdermal formulations of the psychedelic N,N-dimethyltryptamine (DMT).

There is considerable evidence from the literature that psychedelics, such as N,N-dimethyltryptamine (DMT), are safe and effective treatments for depression. However, clinical administration to induce psychedelic effects and expensive psychotherapy-assisted treatments likely limit accessibility to the average patient. There is emerging evidence that DMT promotes positive behavioral changes in vivo at sub-hallucinogenic dosages, and depending on the target indication, subjecting patients to high, bolus dosages may not be necessary. Due to rapid metabolic degradation, achieving target levels of DMT in subjects is difficult, requiring IV administration, which poses risks to patients during the intense hallucinogenic and subjective drug effects. The chemical and physical properties of DMT make it an excellent candidate for non-invasive, transdermal delivery platforms. This paper outlines the formulation development, in vitro, and in vivo testing of transdermal drug-in-adhesive DMT patches using various adhesives and permeation enhancers. In vivo behavioral and pharmacokinetic studies were performed with lead patch formulation (F5) in male and female Swiss Webster mice, and resulting DMT levels in plasma and brain samples were quantified using LC/MS/MS. Notable differences were seen in female versus male mice during IV administration; however, transdermal administration provided consistent, extended drug release at a non-hallucinogenic dose. The IV half-life of DMT was extended by 20-fold with administration of the transdermal delivery system at sub-hallucinogenic plasma concentrations not exceeding 60 ng/mL. Results of a translational head twitch assay (a surrogate for hallucinogenic effects in non-human organisms) were consistent with absence of hallucinations at low plasma levels achieved with our TDDS. Despite the reported low bioavailability of DMT, the non-invasive transdermal DMT patch F5 afforded an impressive 77 % bioavailability compared to IV at two dosages. This unique transdermal delivery option has the potential to provide an out-patient treatment option for ailments not requiring higher, bolus doses and is especially intriguing for therapeutic indications requiring non-hallucinogenic alternatives.

Alcohol and drug presence in traffic crash fatalities before and after the COVID-19 pandemic: Evaluation of the fatality analysis reporting system (FARS) and linked medical examiner-vital records data in Clackamas, Multnomah, and Washington County, Oregon, 2019-2021.

Traffic fatalities, with and from increased risky behaviors (reduced seat belt use, increased impairment from licit and illicit substances), have been increasing, especially during the COVID-19 pandemic. Death certificates are a major source of epidemiologic data in the United States, but have known underreporting of drug and alcohol presence. The Fatality Analysis Reporting System (FARS) is one major source of data on fatal crashes with intoxication. This study links FARS data for three counties in Oregon (2019-2021) with local medical examiner and death certificate data (FARS source data) and compares their concordance with blood alcohol concentration and toxicology for three major drug classes by year. For drivers only, our study finds good concordance between FARS and its source data in 2019 but poor concordance in 2020. This discordance may impact future analysis of impaired crash deaths, and we list some suggestions for amelioration.

Variation in fine-scale water table depth drives abundance of a unique semi-terrestrial crayfish species.

With anthropogenic changes altering the environment and the subsequent decline of natural habitats, it can be challenging to predict essential habitats for elusive and difficult to study taxa. Primary burrowing crayfish are one such group due to the complexity in sampling their semi-terrestrial, subterranean habitat. Sampling burrows usually requires a labor-intensive, time-consuming excavation or trapping process. However, limited information on burrowing crayfish suggests that fine-scale habitat variation may drive burrowing crayfish habitat choice. This project aimed to evaluate the fine-scale habitat characteristics that influence burrowing crayfish presence and abundance at a large, restored-remnant grassland preserve in north-central Illinois. We documented burrow abundance and quadrat-specific habitat variables such as root biomass, canopy cover, apparent seasonal high-water table (water table) depth and dominant vegetation at sites with and without burrowing crayfish populations. Data was recorded at every quadrat and analyzed using generalized linear mixed models. A total of 21 models were created to determine what habitat variables affected burrow presence and abundance. We found that the water table depth was a significant driver of burrow presence and abundance. Root biomass and vegetation cover were not significant drivers, although they did show up in the final models, explaining the data. These findings demonstrate empirical support for previous observations from other burrowing crayfish research and demonstrate the influence of fine-scale habitat when modeling elusive taxa requirements.

GDF15 knockout does not substantially impact perinatal body weight or neonatal outcomes in mice.

Growth differentiation factor-15 (GDF15) increases in circulation during pregnancy and has been implicated in food intake, weight loss, complications of pregnancy, and metabolic illness. We used a Gdf15 knockout mouse model (Gdf15-/- ) to assess the role of GDF15 in body weight regulation and food intake during pregnancy. We found that Gdf15-/- dams consumed a similar amount of food and gained comparable weight during the course of pregnancy compared to Gdf15+/+ dams. Insulin sensitivity on gestational day 16.5 was also similar between genotypes. In the postnatal period, litter size, and survival rates were similar between genotypes. There was a modest reduction in birth weight of Gdf15-/- pups, but this difference was no longer evident postnatal day 3.5 to 14.5. We observed no detectable differences in milk volume production or milk fat percentage. These data suggest that GDF15 is dispensable for changes in food intake, and body weight as well as insulin sensitivity during pregnancy in a mouse model.

Once-weekly insulin efsitora alfa: Design and rationale for the QWINT phase 3 clinical development programme.

AIMS: Insulin efsitora alfa (efsitora) is a once-weekly basal insulin. This review describes the study design and rationale of the efsitora phase 3 Once Weekly (QW) Insulin Therapy (QWINT) clinical development programme, including the five trials, QWINT-1 through QWINT-5. MATERIALS AND METHODS: The five trials included insulin-naïve adults (QWINT-1 and -2) with type 2 diabetes (T2D), adults with T2D previously treated with basal insulin (QWINT-3 and -4), and QWINT-5 in adults with type 1 diabetes. All five trials were designed as multicentre, randomized, controlled, open-label, treat-to-target studies to investigate the efficacy and safety of efsitora versus active once-daily basal insulin comparators (insulin glargine U100 or insulin degludec U100). The primary objective of each trial is to compare the change in HbA1c from baseline to week 26 or 52 between efsitora and the active comparator. The key secondary objectives include change in fasting glucose, insulin dose and continuous glucose monitoring variables, and patient-reported outcome questionnaires. CONCLUSIONS: The QWINT development programme includes a racially and geographically diverse population to provide important information regarding the efficacy and safety of efsitora and its clinical management of people with diabetes.

A Case of Persistent Junctional Reciprocating Tachycardia Coincident With Cor Triatriatum Sinister.

Persistent junctional reciprocating tachycardia is a rare form of refractory atrioventricular reentrant tachycardia that accounts for <1% of supraventricular tachycardia in pediatrics. The accessory pathways are generally isolated with few reported underlying structural heart defects. We present a case of a five-month-old male with refractory tachyarrhythmia found to have cor triatriatum sinister, which to our knowledge, is the first reported case of these two rare anomalies coexisting.