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Abstract Introduction: The Wood Thrush is a migratory bird that has experienced dramatic declines in its populations in recent decades. This species overwinters in forest fragments with intermediate levels of habitat modification in Central America. However, more studies detailing the use of remnant forests through time are needed to elucidate the threats this species faces in the wintering grounds. Objective: To understand the effects of environmental and forest structure variables on the occupancy of Wood Thrush in Northern Costa Rica. Methods: The study area was the Área de Conservación Guanacaste (ACG), located in Northern Costa Rica, in December 2016, and during the 2018-2019 migration season. We estimated Wood Thrush occupancy and detection probability in four locations of ACG (dry forest, cloud forest, and two locations in the wet forest) using single-season occupancy models. We also estimated Wood Thrush occupancy and probability of persistence in different months in three vegetation types (open area, secondary forest, and old-growth forest) in the wet forest of ACG using a multi-season occupancy model approach. Results: Wood Thrush occupancy was best described by precipitation in the four locations of the ACG; the probability of occupancy increased with precipitation. The average occupancy of Wood Thrushes varied with vegetation type: open area with shrubs and forest edge (0.69 ± 0.09), secondary forest (0.46 ± 0.1), and old-growth forest (0.61 ± 0.1). Wood Thrush probability of persistence responded partially to changes in precipitation, with an unexpected increase in persistence when the rainfall continued decreasing in the season. Conclusion: Wood Thrush occupancy was best predicted by changes in precipitation considering a larger spatial scale. Its probability of persistence partially varied with precipitation. An increase in persistence closer to Spring migration might be explained by the start of the breeding season of resident birds, potentially reducing territorial conflicts and conserving energy before migration. The long-term protection of wet forests in Northern Costa Rica is of paramount importance for the conservation of Wood Thrushes in their wintering grounds.

Resumen Introducción: El Zorzal del Bosque es un ave migratoria que ha experimentado caídas dramáticas en sus poblaciones en las últimas décadas. Esta especie pasa el invierno en fragmentos de bosque con niveles intermedios de modificación de hábitat en Centroamérica. Sin embargo, se necesitan más estudios que detallen el uso de los bosques remanentes a lo largo del tiempo para dilucidar las amenazas que enfrenta esta especie en las zonas de invernada. Objetivo: Comprender los efectos de variables ambientales y de estructura del bosque en la ocurrencia del Zorzal del Bosque en el Norte de Costa Rica. Métodos: El área de estudio fue el Área de Conservación Guanacaste (ACG), ubicada en el Norte de Costa Rica, en diciembre de 2016, y en la temporada migratoria 2018-2019. Estimamos la ocurrencia y la probabilidad de detección del Zorzal del Bosque en cuatro ubicaciones de ACG (bosque seco, bosque nuboso y dos ubicaciones en el bosque húmedo) utilizando modelos de ocurrencia de una sola temporada. También estimamos la ocurrencia del Zorzal del Bosque y la probabilidad de persistencia en diferentes meses en tres tipos de vegetación (área abierta, bosque secundario y bosque primario) en el bosque húmedo de ACG utilizando un enfoque de modelo de ocurrencia multi-estacional. Resultados: La ocurrencia del Zorzal del Bosque estuvo mejor descrita por la precipitación en las cuatro localidades del ACG; la probabilidad de ocurrencia aumentó con las precipitaciones. La ocurrencia media de zorzales varió con el tipo de vegetación: área abierta con arbustos y borde de bosque (0.69 ± 0.09), bosque secundario (0.46 ± 0.1) y bosque primario (0.61 ± 0.1). La probabilidad de persistencia del zorzal respondió parcialmente a cambios en la precipitación, con un aumento inesperado en la persistencia cuando las precipitaciones continuaron disminuyendo en la temporada. Conclusión: La ocurrecia del Zorzal del Bosque varió con la precipitación considerando una escala espacial mayor. Su probabilidad de persistencia varió parcialmente con la precipitación. Un aumento en la persistencia más cerca de la migración de primavera podría explicarse por el inicio de la temporada de reproducción de las aves residentes, lo que podría reducir los conflictos territoriales y conservar energía antes de la migración. La protección a largo plazo de los bosques húmedos en el norte de Costa Rica es de suma importancia para la conservación de los Zorzales del Bosque en sus zonas de invernada.

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The soft tick Ornithodoros turicata Duges (Acari: Argasidae) is a potential vector of African swine fever virus (ASFV). We evaluated the efficacy of two methods to collect soft ticks rapidly and efficiently from gopher tortoise (Gopherus polyphemus) burrows, which are ubiquitous throughout large regions of the southeastern United States and their burrows are a known microhabitat of O. turicata. Burrow vacuuming was an effective and efficient tick collection method; no tick was captured employing CO2 trapping. Using an occupancy modelling framework, we estimated that the probability of detecting ticks from an infested burrow each time a sample was taken with this method was 58% and increased with the average relative humidity. With the occupancy model, we estimated that 70% of the burrows in the study area were infested with O. turicata. Manual sifting of the burrow material yielded more ticks (6.6 individuals/sample) than using a set of three sieves (2.9 individuals/sample), yet the probability of detecting the species was not different between the two methods (Pval = 0.7). These methods can inform the development of ASF vector surveillance and outbreak response plans in areas of high risk for ASFV introduction in the region.

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Objectives: While extensive research has focused on patient outcomes in skilled nursing facilities, a critical gap remains in understanding factors influencing their managerial performance, particularly occupancy rates. This study examines the occupancy rates of skilled nursing facilities and assesses the significance of two important drivers of managerial performance that have not received sufficient attention-the influence of payer mix and total profit margin. Specifically, we focused on the role played by a nursing home's financial performance (as assessed by profit margin) in influencing the relationship between payer mix and occupancy rate among skilled nursing facilities. Methods: Data were extracted from the 2019 to 2020 Joint Annual Report of Nursing Homes for a sample of 612 skilled nursing facilities in Tennessee, USA. Regression analysis was performed by fitting a generalized estimating equation of occupancy rate. Results: Compared to skilled nursing facilities in the lowest quartile of profit margin, for example, those in the highest quartile had approximately 18 percentage points higher occupancy rates per unit increase in resident days of care covered by traditional Medicare (ß = 0.18, p = 0.0028). Similarly, skilled nursing facilities in the second highest quartile of profit margin had a higher occupancy rate by approximately 23 percentage points per unit increase in Medicare Advantage (ß = 0.23, p = 0.0375) when compared to those in the lowest quartile of profit margin. Conclusions: Skilled nursing facilities with stronger financial performance generally have higher occupancy rates, particularly notable in relation to an upswing in payer sources such as traditional Medicare and Medicare Advantage, when compared to skilled nursing facilities with weaker profitability. Given the increasingly larger role of Medicare in long-term care funding, policymakers and nursing home managers may find it useful to consider our findings when evaluating opportunities to enhance managerial performance of skilled nursing facilities.

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INTRODUCTION: Chronic spontaneous urticaria (CSU) is characterized by urticaria persisting for more than 6 weeks. Antihistamines, notably sgAH (second generation antihistamines) are the first line of treatment for CSU. AREAS COVERED: This consensus aimed to review the existing research on receptor occupancy of antihistamines, including levocetirizine, and translate its implications in the treatment of CSU. The consensus deliberations were under the banner of the Antihistamine Receptor Occupancy Group (AROG) from India, an expert panel of 12 dermatologists with a mix of institutional and practitioner backgrounds. This group analyzed the existing translational research on the receptor occupancy of levocetirizine to establish the clinical efficacy and safety of levocetirizine in the treatment of CSU using the grading of recommendations assessment, development, and evaluation (GRADE) method vis-a-vis the varied SGAH. EXPERT OPINION: SGAH constitute the first step in the therapeutic ladder for managing CSU. Levocetirizine has high bioavailability, high affinity and occupancy of the H1 receptor, rapid onset of action, limited distribution and minimal hepatic metabolism. It exhibits significant anti-inflammatory effects at clinically relevant concentrations. The marked receptor occupancy translates to enhanced efficacy as compared to similarly dosed SGAH with the lower cost making it an appropriate drug for chronic use. Receptor occupancy should be the basis of intra-class head-to-head trials in CSU.

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BACKGROUND: We recently reported that Mediterranean (MED) and green-MED diets significantly attenuated age-related brain atrophy by ∼50% within 18 months. OBJECTIVE: To explore the contribution of specific diet-induced parameters to brain volume deviation from chronological age. METHODS: A post-hoc analysis of the 18-month DIRECT-PLUS trial, where participants were randomly assigned to: (1)-healthy-dietary-guidelines (HDG); (2)-MED diet; or (3)-green-MED diet, high in polyphenols and low in red meat. Both MED groups consumed 28g walnuts/day (+440mg/day polyphenols). The green-MED group further consumed green-tea (3-4 cups/day) and Mankai green shake (Wolffia-globosa aquatic plant) (+800mg/day polyphenols). We collected blood samples through the intervention and followed brain structure volumes by magnetic-resonance-imaging (MRI). We used hippocampal-occupancy (HOC) score (hippocampal and inferior-lateral-ventricle volumes ratio) as a neurodegeneration marker and brain age proxy. We applied multivariate-linear-regression models. RESULTS: Of 284 participants (88% male; age=51.1years; BMI=31.2kg/m2; HbA1c=5.48%; APOE-ε4 genotype=15.7%), 224 completed the trial with eligible whole-brain MRIs. Individuals with higher HOC-deviations (i.e., younger brain age) presented lower body weight (r=-0.204;95%CI[-0.298,-0.101]), waist-circumference (r=-0.207;95%CI[-0.310,-0.103]), diastolic (r=-0.186;95%CI[-0.304,-0.072]), and systolic blood pressure (r=-0.189;95%CI[-0.308,-0.061]), insulin (r=-0.099;95%CI[-0.194,-0.004]) and HbA1c (r=-0.164;95%CI[-0.337,-0.006]) levels. After 18 months, greater changes in HOC-deviations (i.e., brain-age decline attenuation) were independently associated with improved HbA1c (ß=-0.254;95%CI[-0.392,-0.117]), HOMA-IR (ß=-0.200;95%CI[-0.346,-0.055]) fasting glucose (ß=-0.155;95%[CI -0.293,-0.016]), and s-CRP (ß=-0.153;95%[CI -0.296,-0.010]). Improvement in diabetes status was associated with greater HOC-deviation changes compared to either no change in diabetes status (0.010;95%CI]0.002,0.019[) or with an unfavorable change (0.012;95%CI]0.002,0.023]). A decline in HbA1c is further associated with greater deviation changes in the Thalamus, Caudate nucleus, and Cerebellum (p<0.05). Greater consumption of Mankai and green-tea (green-MED diet components) were associated with greater HOC-deviation changes beyond weight loss. CONCLUSIONS: Glycemic control contributes to the neuroprotective effects of the MED and green-MED diets on brain age. Polyphenols-rich diet components as Mankai and green-tea may contribute to a more youthful brain age. TRIAL-REGISTRATION-CLINICAL-TRIALS-IDENTIFIER: NCT03020186 URL OF REGISTRATION: https://clinicaltrials.gov/study/NCT03020186.

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Schistosomiasis, caused by trematodes of genus Schistosoma, is among the most seriously neglected tropical diseases. Although rapid surveillance of risk areas for Schistosoma transmission is vital to control schistosomiasis, the habitat and infection status of this parasite are difficult to assess. Environmental DNA (eDNA) analysis, involving the detection of extra-organismal DNA in water samples, facilitates cost-efficient and sensitive biomonitoring of aquatic environments and is a promising tool to identify Schistosoma habitat and infection risk areas. However, in tropical wetlands, highly turbid water causes filter clogging, thereby decreasing the filtration volume and increasing the risk of false negatives. Therefore, in this study, we aimed to conduct laboratory experiments and field surveys in Lake Victoria, Mbita, to determine the appropriate filter pore size for S. mansoni eDNA collection in terms of particle size and filtration volume. In the laboratory experiment, aquarium water was sequentially filtered using different pore size filters. Targeting >3 µm size fraction was found to be sufficient to capture S. mansoni eDNA particles, regardless of their life cycle stage (egg, miracidia, and cercaria). In the field surveys, GF/D (2.7 µm nominal pore size) filter yielded 2.5-times the filtration volume obtained with a smaller pore size filter and pre-filtration methods under the same time constraints. Moreover, a site-occupancy model was applied to the field detection results to estimate S. mansoni eDNA occurrence and detection probabilities and assess the number of water samples and PCR replicates necessary for efficient eDNA detection. Overall, this study reveals an effective method for S. mansoni eDNA detection in turbid water, facilitating the rapid and sensitive monitoring of its distribution and cost-effective identification of schistosomiasis transmission risk areas.

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More than 240 species of snake have been described from Thailand, yet basic natural history and ecology for this group of animals remains scarce in human disturbed environments despite conservation and human medical significance of them in these habitats. We studied snake diversity at Walailak University from March to December 2023, the largest university campus in Thailand (1525 hectares) through standardized walking surveys, opportunistic notifications and observation, road surveys, and traps and evaluated diversity using the Shannon diversity index (H), Pielou's evenness of species (J), detection probabilities (p), and occupancy probabilities (ψ). We observed 195 snakes (21 species, 7 families) at Walailak University and overall snake diversity (H = 2.60) and evenness (J = 0.85) were quite high, although specific site diversity (range H = 0-1.94) and evenness (range J = 0.67-0.91) within the university were variable. The probability of detecting snakes (range p = .10-.40) increased with increasing humidity and decreased with increasing amount of rain, temperature, and wind; site occupancy probability decreased with increased canopy height and increased with increased distance to buildings, increased canopy height loss, increased distance to roads, and increased distance to water. Our findings of relatively high snake diversity, presence of snake species potentially dangerous to humans (six species), and protected snake species (Thailand WARPA and international CITES, five species) suggest significant potential for conservation and further research at Walailak University and other campuses in Thailand.

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BACKGROUND: During the COVID-19 pandemic, in South Korea, general wards in several hospitals were converted to temporary negative pressure isolation (TNPI) wards by using portable high-efficiency particulate air (HEPA) filter units (PHUs). This study proposes improvements to TNPI ward to prepare for airborne infectious diseases. METHODS: Existing air-conditioning systems and the systems' operation status were investigated during the pandemic in four hospitals through a document review and field investigation with staff interviews. On-site experiments and measurements were conducted under vacant conditions. Differential pressure (∆P) between spaces was measured in all four hospitals while tracer gas tests were carried out in two hospitals. RESULTS: The investigation revealed that thermal discomfort caused the existing systems remaining perpetually active. Additionally, the noise generated by the PHU caused an unexpected shutdown of that equipment. The ∆P of over -2.5 Pa was measured as a result of the operating status of equipment. As a result, it was determined that these situations caused duct backflow and gas diffusion through unsealed diffusers. Moreover, low airtightness of existing facilities can affect indoor environment, pressure difference, and gas diffusion. CONCLUSIONS: When using existing facilities as TNPI wards, the architectural airtightness and existing air-conditioning systems should be considered. We concluded that it is important to increase the airtightness and seal unused diffusers in order to prevent cross-infection by unpredictable airflow.

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Carnivores play key roles in maintaining ecosystem structure and function as well as ecological processes. Understanding how sympatric species coexist in natural ecosystems is a central research topic in community ecology and biodiversity conservation. In this study, we explored intra- and interspecific niche partitioning along spatial, temporal, and dietary niche partitioning between apex carnivores (wolf Canis lupus, snow leopard Panthera uncia, Eurasian lynx Lynx lynx) and mesocarnivores (Pallas's cat Otocolobus manul, red fox Vulpes vulpes, Tibetan fox Vulpes ferrilata) in Qilian Mountain National Park, China, using camera trapping data and DNA metabarcoding sequencing data. Our study showed that apex carnivore species had more overlap temporally (coefficients of interspecific overlap ranging from 0.661 to 0.900) or trophically (Pianka's index ranging from 0.458 to 0.892), mesocarnivore species had high dietary overlap with each other (Pianka's index ranging from 0.945 to 0.997), and apex carnivore and mesocarnivore species had high temporal overlap (coefficients of interspecific overlap ranging from 0.497 to 0.855). Large dietary overlap was observed between wolf and snow leopard (Pianka's index = 0.892) and Pallas's cat and Tibetan fox (Pianka's index = 0.997), suggesting the potential for increased resource competition for these species pairs. We concluded that spatial niche partitioning is likely to key driver in facilitating the coexistence of apex carnivore species, while spatial and temporal niche partitioning likely facilitate the coexistence of mesocarnivore species, and spatial and dietary niche partitioning facilitate the coexistence between apex and mesocarnivore species. Our findings consider partitioning across temporal, spatial, and dietary dimensions while examining diverse coexistence patterns of carnivore species in Qilian Mountain National Park, China. These findings will contribute substantially to current understanding of carnivore guilds and effective conservation management in fragile alpine ecosystems.

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Avidin-biotin binding, the most robust non-covalent protein-ligand interaction occurring in nature, has wide-ranging applications in biotechnology. A frequent challenge in these applications is accurately determining the number of unoccupied biotin binding sites in avidin-containing fusion proteins. We delineate a novel assay protocol in miniaturized format to quantify available biotin binding sites based on the affinity of the anionic dye 4'-hydroxyazobenzene-2-carboxylic acid for biotin binding sites within avidin. We apply this assay as a quality control assay to evaluate the number of available biotin binding sites in different fusion protein production batches. This method offers a streamlined alternative to fluorescence-based assays commonly employed to assess biotin binding, is less time-consuming than other methods and is applicable to diverse fusion proteins.

The avidin-biotin interaction is a robust protein-ligand interaction utilized for several applications. We have developed a miniaturized assay protocol using the small molecule dye HABA to quantify the available biotin binding sites in avidin-containing fusion proteins. This method also serves as a quality control assay for different batches of assembled avidin-biotin fusion proteins, reducing technical complexities and time required for batch release.

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BACKGROUND: Intensive medical care units (IMCUs) usually admit patients who are in critical medical need and require the utmost attention of healthcare professionals, along with the best treatment options available. These patients are prone to infections and require various antibiotics for the treatment. Varying costs of antibiotics, variable dosage forms, and antibiotic resistance cause an economic burden on patients Methodology: This study was designed and conducted prospectively to evaluate the prescribing pattern of antibiotics at the IMCU in a tertiary care hospital. A total of 102 patients were included in the study based on the exclusion and inclusion criteria, and the collected data was tabulated in an Excel sheet and analyzed using Prism GraphPad software. Data were presented as numbers and percentages. RESULTS: Most of the patients were in the age group of 41-50 years. The number of male patients was slightly more than that of female patients. The majority of the patients admitted to the IMCU had acute pulmonary edema and cerebrovascular accidents. Most antibiotics were prescribed empirically and administered parenterally, of which Amoxicillin + Potassium clavulanate was the most commonly used antibiotic. Tigecycline had the highest daily defined dose per 100 bed days value, and injection Sulbactam + Cefoperazone was the costliest of all antibiotic therapy. CONCLUSION: Antibiotic therapy used in the IMCU consisting of Sulbactam + Cefoperazone was found to be costlier, and Amoxicillin + Potassium clavulanate were the commonly prescribed antibiotics among the other prescribed antibiotics. The average cost of antibiotics was found to be higher, which increased the economic healthcare burden for patients and their families.

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Monitoring programs are pivotal to establishing sound management. Due to economic, logistic, and time limitations, monitoring programs often overlook differences among life-history stages. However, species occurrence does not necessarily mean population viability, and it is unclear to what extent monitoring programs that do not consider separately adult presence and reproduction provide effective management indications. Unfortunately, collecting data on certain life stages requires high sampling effort, leading to a trade-off between model reliability and resources needed for monitoring. We collected data on presence and reproduction of amphibians by monitoring 207 waterbodies in Lombardy (northern Italy) in 2017-2022. We then used multistate occupancy models to test whether certain environmental features, namely, pond area, hydroperiod, forest cover, shade, aquatic vegetation, and predators' presence, differentially affected adult occurrence and breeding probabilities of multiple amphibian species. To assess optimal sampling efforts, we modeled the detection probabilities of adults and reproduction across multiple species. Finally, we identified the optimal monitoring strategy under different scenarios of resource availability, comparing adult-only monitoring versus joint assessment of the occurrence of adults and reproduction. In many cases, the main drivers of adult occurrence and reproduction did not coincide because most investigated ecological variables affected one life stage or the other. Forest area, for instance, increased occurrence probabilities of adults of the endemic Rana latastei but showed no effect on their reproduction probabilities. Quantitative estimates of the sampling effort showed that occurrence of adults was easier to spot in 4 out of 7 species. Multicriteria decision analyses showed that when resources were scarce, monitoring adults was the optimal strategy for those 4 species. Conversely, with more resources, monitoring both adults and reproduction emerged as the best strategy for all the considered species. Integrated monitoring of adults and reproduction is essential to comprehensively identify effective conservation measures for amphibians.

Integración de datos de presencia adulta y de reproducción para identificar medidas de conservación para los anfibios Resumen Los programas de monitoreo son fundamentales para establecer una gestión adecuada. Debido a limitaciones económicas, logísticas y de tiempo, los programas de seguimiento suelen pasar por alto las diferencias entre las distintas fases del ciclo de vida. Sin embargo, la presencia de especies no significa necesariamente la viabilidad de la población, y no está claro hasta qué punto los programas de seguimiento que no consideran por separado la presencia de adultos y la reproducción proporcionan indicaciones eficaces para la gestión. Desgraciadamente, la recolección de datos sobre etapas determinadas del ciclo de vida requiere un gran esfuerzo de muestreo, lo que lleva a un compromiso entre la fiabilidad del modelo y los recursos necesarios para el seguimiento. Recopilamos datos sobre la presencia y reproducción de anfibios mediante el monitoreo de 207 cuerpos de agua en Lombardía (norte de Italia) entre 2017 y 2022. Después utilizamos modelos de ocupación multiestado para comprobar si determinadas características ambientales (superficie de los estanques, hidroperiodo, cubierta forestal, sombra, vegetación acuática y presencia de depredadores) afectaban de forma diferencial la presencia de adultos y a las probabilidades de reproducción de múltiples especies de anfibios. Para evaluar los esfuerzos de muestreo óptimos, modelamos las probabilidades de detección de adultos y reproducción de múltiples especies. Por último, identificamos la estrategia de seguimiento óptima en diferentes escenarios de disponibilidad de recursos y comparamos el seguimiento exclusivo de adultos frente a la evaluación conjunta de la presencia de adultos y reproducción. En muchos casos, los principales factores en la presencia de adultos y en la reproducción no coincidían, ya que la mayoría de las variables ecológicas investigadas afectaban a una u otra etapa del ciclo. La cubierta forestal, por ejemplo, aumentó la probabilidad de presencia de adultos de la especie endémica Rana latastei pero no mostraron un efecto sobre su probabilidad de reproducción. Las estimaciones cuantitativas del esfuerzo de muestreo mostraron que la presencia de adultos era más fácil de detectar en cuatro de las siete especies. Los análisis de decisión multicriterio mostraron que, cuando los recursos eran escasos, el seguimiento de los adultos era la estrategia óptima para esas cuatro especies. Por el contrario, con más recursos, el seguimiento tanto de los adultos como de la reproducción resultó ser la mejor estrategia para todas las especies consideradas. El seguimiento integrado de los adultos y la reproducción es esencial para identificar de forma exhaustiva medidas de conservación eficaces para los anfibios.

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The microstructure of the electrocatalyst plays a critical role in the reaction efficiency and stability during electrochemical water splitting. Designing an efficient and stable electrocatalyst, further clarifying the synthesis mechanism, is still an important problem to be solved urgently. Inspired by the copper pyrometallurgy theory, an exceptionally active NiMo/CF(N) electrode, consisting of an ant-nest-like copper foam substrate (defined as CF(N)) and deposited NiMo layer, was fabricated for the alkaline hydrogen evolution reaction (HER). Our findings expounded the structure construction mechanism and highlighted the pivotal role of the spatial occupancy of sulfur atoms in the construction of the ant-nest-like structure. The NiMo/CF(N) composite, characterized by channels with a 2 µm diameter, showcases strong electronic interactions, increased catalytic active sites, enhanced electron/ion transport, and facilitated gas release during HER. Remarkably, NiMo/CF(N) demonstrates ultralow overpotentials of 21 mV to deliver a current density of 10 mA cm-2 in 1 M KOH. This electrode also exhibits outstanding durability, maintaining a current density of 200 mA cm-2 for 110 h, attributed to the chemical and structural integrity of its catalytic surface and the excellent mechanical properties of the electrode. This work advances the fundamental understanding of constructing micro/nano-structured electrocatalysts for highly efficient water splitting.

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The serotonin 2A (5-HT2A) receptor is an important target for drug development and the main receptor through which classical psychedelics elucidate their hallucinogenic effects. The 5-HT2A receptor antagonist ketanserin has frequently been used as a tool to block the receptor. Here, we establish the dose-occupancy relation of ketanserin and the cerebral 5-HT2A receptor in healthy participants by conducting a positron emission tomography (PET) study. 120-min PET scans using the 5-HT2A receptor agonist radiotracer [11C]Cimbi-36 were conducted at baseline and after oral doses of either 10, 20, or 40 mg of ketanserin; each participant underwent one or two scans after ketanserin administration. Occupancy was defined as the percent change in neocortex binding potential (BPND), estimated using the simplified reference tissue model (SRTM) with the cerebellum as reference region. Peroral ketanserin intake resulted in a plasma concentration-related increase in cerebral 5-HT2A receptor occupancy with the highest plasma ketanserin concentrations measured after ∼2 h. The relation between mean plasma ketanserin concentrations and 5-HT2A receptor occupancy conformed to a single-site binding model with an estimated EC50 (95 % CI) of 2.52 (0.75; 8.1) ng/mL, which corresponds to a peroral dose of ketanserin of approximately 10 mg. These data elucidate for the first time in humans the cerebral pharmacodynamics of ketanserin, both benefitting its use as a pharmacological tool for probing brain function and adding to its potential for therapeutic use in rescuing a bad psychedelic experience.

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The rise of Express Lanes also known as High Occupancy Toll (HOT) Lanes and Managed Lanes, signifies a major leap in traffic management and transportation funding. Despite their increased deployment to ensure reliable travel times through dynamic tolling during peak traffic periods, a comprehensive evaluation of their safety impact is notably lacking. Presently, the Crash Modification Factors Clearinghouse, a vital resource, only lists two case studies related to Express Lanes, one of which is our own research. This lack of data highlights the critical need for more extensive studies to thoroughly assess the safety benefits of Express Lanes and to improve their application. This study aims to rigorously evaluate the safety impact of express lanes on freeways, presenting a first-of-its-kind, in-depth analysis of their specific effects on both Express Lanes and General-Purpose Lanes (GP-Lanes) individually. The analysis utilized data from 55 miles of Express Lanes across various locations in Florida, comparing them to High Occupancy Vehicle (HOV) lanes. The results demonstrate that converting HOV lanes to Express Lanes or introducing new ones does not compromise overall freeway safety. In fact, safety within Express Lanes improves, as evidenced by a decrease in crash occurrence and Crash Modification Factors for Express lanes, which are below "1" across all crash categories. This underscores the effectiveness of Express lanes in enhancing roadway safety. In contrast, incidents in GP-Lanes have increased, indicating a shift of crashes to these lanes, and thus making Express lanes relatively safer. This underlines the importance of continued research into the safety impact of express lanes and calls for further studies to refine traffic management strategies, aiming at enhancing travel efficiency while ensuring traffic safety, especially for the GP-Lanes amid the expansion of express lanes.

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This study explores how climate variables influenced the evolution and diversification of Neurergus newts within the Irano-Anatolian biodiversity hotspot. We use a dated phylogenetic tree and climatic niche models to analyze their evolutionary history and ecological preferences. Using genetic data from nuclear (KIAA) and mitochondrial (16s and 12s) genes, we estimate divergence times and identify four major Neurergus clades. The initial speciation event occurred approximately 11.3 million years ago, coinciding with the uplift of the Zagros and Anatolian mountains. This geological transformation isolated newt populations, likely triggering the first speciation event. By integrating potential geographic distribution with climate variables, we reconstruct ancestral niche occupancy profiles. This highlights the critical roles of temperature and precipitation in shaping Neurergus habitat preferences and distribution. We observe both phylogenetic niche conservatism and divergence, with niche divergence playing a dominant role in diversification. This research emphasizes the complex interplay of geography, climate, and ecology in speciation and the vulnerability of isolated mountain newt populations to environmental changes.

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Three models/methods are given to understand the extreme international variation in available and occupied hospital bed numbers. These models/methods all rely on readily available data. In the first, occupied beds (rather than available beds) are used to measure the expressed demand for hospital beds. The expressed occupied bed demand for three countries was in the order Australia > England > USA. Next, the age-standardized mortality rate (ASMR) has dual functions. Less developed countries/regions have low access to healthcare, which results in high ASMR, or a negative slope between ASMR versus available/occupied beds. In the more developed countries, high ASMR can also be used to measure the 'need' for healthcare (including occupied beds), a positive slope among various social (wealth/lifestyle) groups, which will include Indigenous peoples. In England, a 100-unit increase in ASMR (European Standard population) leads to a 15.3-30.7 (feasible range) unit increase in occupied beds per 1000 deaths. Higher ASMR shows why the Australian states of the Northern Territory and Tasmania have an intrinsic higher bed demand. The USA has a high relative ASMR (for a developed/wealthy country) because healthcare is not universal in the widest sense. Lastly, a method for benchmarking the whole hospital's average bed occupancy which enables them to run at optimum efficiency and safety. English hospitals operate at highly disruptive and unsafe levels of bed occupancy, manifesting as high 'turn-away'. Turn-away implies bed unavailability for the next arriving patient. In the case of occupied beds, the slope of the relationship between occupied beds per 1000 deaths and deaths per 1000 population shows a power law function. Scatter around the trend line arising from year-to-year fluctuations in occupied beds per 1000 deaths, ASMR, deaths per 1000 population, changes in the number of persons hidden in the elective, outpatient and diagnostic waiting lists, and local area variation in births affecting maternity, neonatal, and pediatric bed demand. Additional variation will arise from differences in the level of local funding for social care, especially elderly care. The problems associated with crafting effective bed planning are illustrated using the English NHS as an example.

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INTRODUCTION: Traditionally, wards in acute care hospitals consist predominately of multioccupancy bays with some single rooms. There is an increasing global trend towards a higher proportion of single rooms in hospitals, with the UK National Health Service (NHS) advocating for single-room provision in all new hospital builds. There is limited evidence on the impact of a ward environment incorporating mostly single and some multioccupancy bays on patient care and organisational outcomes. METHODS AND ANALYSES: This study will assess the impact of a newly designed 28-bedded ward environment, with 20 single rooms and two four-bedded bays, on patient and staff experiences and outcomes in an acute NHS Trust in East England. The study is divided into two work packages (WP)-WP1 is a quantitative data extraction of routinely collected patient and staff data while WP2 is a mixed-methods process evaluation consisting of one-to-one, in-depth, semistructured interviews with staff, qualitative observations of work processes on the ward and a quantitative data evaluation of routinely collected process evaluation data from patients and staff. ETHICS AND DISSEMINATION: Ethical approval was obtained from the UK Health Research Authority (IRAS ID: 334395). Study findings will be shared with key stakeholders, published in peer-reviewed high-impact journals and presented at relevant conferences.

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BACKGROUND: Burn injuries are a significant public health concern, closely linked to housing conditions and socioeconomic status. Residents in socioeconomically deprived neighbourhoods are at increased risk of exposure to hazards due to older and poorer housing conditions and limited access to fire protection measures. Individual behaviours such as substance use, smoking, and hoarding are often highlighted as primary causes of residential fires, overshadowing the broader socioeconomic and structural factors that also play a significant role in housing safety. This paper explores the correlation between inadequate housing conditions and heightened fire risks leading to burn injuries, focusing on the contextual factors shaping everyday urban fire risks, experiences, and responses of residents living in Single-Room Occupancy (SRO) housing in Vancouver's Downtown East Side (DTES) and staff working in the fire, health, housing (social and private), and non-profit sectors. METHODS: As part of an ongoing ethnographic study, we partnered with the Vancouver Fire Rescue Services (VFRS) to conduct participant observations in private, non-profit, and government-owned SROs, modular homes, and a temporary shelter. This paper synthesizes insights from participant observations from the first author's self-reflexive journals, including informal conversations with approximately fifty-nine individuals such as SRO tenants, SRO managers/caretakers, health workers, burn survivors, municipal staff, not-for-profit staff, and firefighters. RESULTS: Urgent housing-related issues contributing to inequitable everyday urban fire risks were identified, such as structural deficiencies in SRO buildings and systems, inadequate waste management and storage, and inequitable approaches to addressing hoarding. Additionally, disparities in access to information and the interaction between interpersonal and structural stigmas were significant factors, underscoring the pressing need for intervention. CONCLUSION: Communities like DTES, facing precarious housing conditions, disadvantaged neighbourhoods, and complex health and social challenges, necessitate a comprehensive and holistic approach to fire prevention and safety. Recognizing the interplay between housing instability, mental and physical health issues, unregulated toxic drug supply, drug criminalization, and structural inequities allows practitioners from various sectors to develop contextually driven fire prevention strategies. This multifaceted approach transcends individual-level behaviour change and is crucial for addressing the complex issues contributing to fire risks in underserved communities.

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Quantitative phosphoproteomic data has mostly been reported from experiments comparing relative phosphopeptides intensities in two or more different conditions, while the ideal parameter to compare is phosphopeptides occupancies. This term is scarcely used and therefore barely implemented in phosphoproteomics studies, and this should be of concern for the scientific journals. In order to demonstrate the relevance of this issue, here we show how the method of choice affects the interpretation of the data. The phosphoproteomic profile modulated in two AML cell lines after CK2 inhibition with CIGB-300 or CX-4945 is shown. Following the downstream action of CK2 the phosphosite intensity and occupancy results were compared to validate the best approach for quantitative phosphoproteomic studies. Even when the total number of quantified phosphopeptides was higher by using the intensity calculation, in all the cases the percent of CK2 consensus sequences which were down-regulated in response to CK2 inhibition was higher using the phosphosite occupancy quantification. To note, a high number of CK2 consensus sequences was found down-regulated with at least a 10% or 15% of phosphosite occupancy variation illustrating that low thresholds of occupancy modulation might be indicative of biological effect. Additionally, several biological processes only appear significantly over-represented in the phosphoproteome quantified by occupancy. The functional enrichment analysis per ranges of occupancy variations also illustrated clear differences among AML cell lines subjected to CK2 inhibition by CX-4945. A low overlap between the phosphoproteomes quantified by intensity and occupancy was obtained illustrating that new developments in proteomics techniques are needed to improve the performance of the occupancy approach. Even in such context, results indicate that occupancy quantification performs better than phosphorylation quantification based on intensity reinforcing the importance of such quantification approach to describe phosphoproteomic data.

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