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The Mountain snowpack stores months of winter precipitation at high elevations, supplying snowmelt to lowland areas in drier seasons for agriculture and human consumption worldwide. Accurate seasonal predictions of the snowpack are thus of great importance, but such forecasts suffer from major challenges such as resolving interactions between forcing variables at high spatial resolutions. To test novel approaches to resolve these processes, seasonal snowpack simulations are run at different grid resolutions (50 m, 100 m, 250 m) and with variable forcing data for the water year 2016/2017. COSMO-1E data is either dynamically downscaled with the High-resolution Intermediate Complexity Atmospheric Research (HICAR) model or statistically downscaled to provide forcing data for snowpack simulations with the Flexible Snowpack Model (FSM2oshd). Simulations covering complex terrain in the Swiss Alps are carried out with the operational settings of the FSM2oshd model or with a model extension including wind- and gravitational-induced snow transport (FSM2trans). The simulated snow height is evaluated against observed snow height collected during LiDAR flights in spring 2017. Observed spatial snow accumulation patterns and snow height distribution are best matched with simulations using dynamically downscaled data and the FSM2trans model extension, indicating the importance of both accurate meteorological forcing data and snow transport schemes. This study demonstrates for the first time the effects of applying dynamical downscaling schemes to snowpack simulations at the seasonal and catchment scale.

Xylazine is in the unregulated drug supply at increasing rates, usually combined with fentanyl, necessitating understanding of its pharmacology. Despite commentary from politicians, and public health officials, it is unknown how xylazine impacts naloxone efficacy, and. few studies have examined it alone. Here, we examine the impact of xylazine alone and in combination with fentanyl on several behaviors in mice. Surprisingly, naloxone precipitates withdrawal from xylazine and fentanyl/xylazine coadministration, with enhanced sensitivity in females. Further, xylazine is a full agonist at kappa opioid receptors, a potential mechanism for its naloxone sensitivity. Finally, we demonstrate surprising effects of xylazine to kappa opioid antagonism, which are relevant for public health considerations. These data address an ongoing health crisis and will help inform critical policy and healthcare decisions. One-sentence summary: We present surprising new insights into xylazine and fentanyl pharmacology with immediate implications for clinical practice and frontline public health.

This design case chronicles the efforts of an interdisciplinary team of researchers as they collaborated with middle grades science teachers and students to build and refine an epidemic disease curriculum module. The initial five-day design was delivered in five science classrooms at three nearby schools where researcher classroom observations and teacher feedback drove iterative refinements of the module's materials. The final design of this module consisted of four instructional days of modeling and simulation activities that integrate computational thinking practices, computer science concepts, and life sciences content. The paper aims to illustrate the design motivations to address contextual constraints such as tight curricular schedules and varied levels of exposure to programming for both teachers and students. The instructional materials presented in this design case were the result of a three-year long research-practice partnership with science teachers at nearby middle schools.

Abstract Background Chronic kidney disease (CKD) is highly prevalent among Indigenous Australians, especially those in remote regions. The Tiwi population has been isolated from mainland Australia for millennia and exhibits unique genetic characteristics that distinguish them from other Indigenous and non-Indigenous populations. Notably, the rate of end-stage renal disease is up to 20 times greater in this population compared to non-Indigenous populations. Despite the identification of numerous genetic loci associated with kidney disease through GWAS, the Indigenous population such as Tiwi remains severely underrepresented and the increased prevalence of CKD in this population may be due to unique disease-causing alleles/genes. Methods We used albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) to estimate the prevalence of kidney disease in the Tiwi population (N = 492) in comparison to the UK Biobank (UKBB) (N = 134,724) database. We then performed an exploratory factor analysis to identify correlations among 10 CKD-related phenotypes and identify new multi-phenotype factors. We subsequently conducted a genome-wide association study (GWAS) on all single and multiple phenotype factors using mixed linear regression models, adjusted for age, sex, population stratification, and genetic relatedness between individuals. Results Based on ACR, 20.3% of the population was at severely increased risk of CKD progression and showed elevated levels of ACR compared to the UKBB population independent of HbA1c. A GWAS of ACR revealed novel association loci in the genes MEG3 (chr14:100812018:T:A), RAB36 (rs11704318), and TIAM2 (rs9689640). Additionally, multiple phenotypes GWAS of ACR, eGFR, urine albumin, and serum creatinine identified a novel variant that mapped to the gene MEIS2 (chr15:37218869:A:G). Most of the identified variants were found to be either absent or rare in the UKBB population. Conclusions Our study highlights the Tiwi population’s predisposition towards elevated ACR, and the collection of novel genetic variants associated with kidney function. These associations may prove valuable in the early diagnosis and treatment of renal disease in this underrepresented population. Additionally, further research is needed to comprehensively validate the functions of the identified variants/genes.

Background Cesarean delivery rates have increased globally resulting in a public health concern. We estimate rates of cesarean deliveries among Thai women using the World Health Organization (WHO) Robson Classification system and compare rates by Robson group to the Robson guideline for acceptable rates to identify groups that might benefit most from interventions for rate reduction. Methods In 2017 and 2018, we established cohorts of pregnant women aged ≥ 18 years seeking prenatal care at two tertiary Thai hospitals and followed them until 6–8 weeks postpartum. Three in-person interviews (enrollment, end of pregnancy, and postpartum) were conducted using structured questionnaires to obtain demographic characteristics, health history, and delivery information. Cesarean delivery indication was classified based on core obstetric variables (parity, previous cesarean delivery, number of fetuses, fetal presentation, gestational week, and onset of labor) assigned to 10 groups according to the Robson Classification. Logistic regression was used to identify factors associated with cesarean delivery among nulliparous women with singleton, cephalic, term pregnancies. Results Of 2,137 participants, 970 (45%) had cesarean deliveries. The median maternal age at delivery was 29 years (interquartile range, 25–35); 271 (13%) participants had existing medical conditions; and 446 (21%) had pregnancy complications. The cesarean delivery rate varied by Robson group. Multiparous women with > 1 previous uterine scar, with a single cephalic pregnancy, ≥ 37 weeks gestation (group 5) contributed the most (14%) to the overall cesarean rate, whereas those with a single pregnancy with a transverse or oblique lie, including women with previous uterine scars (group 9) contributed the least (

Abstract Probiotics are widely used in agriculture including commercial beekeeping, but there is little evidence supporting their effectiveness. Antibiotic treatments can greatly distort the gut microbiome, reducing its protective abilities and facilitating the growth of antibiotic resistant pathogens. Commercial beekeepers regularly apply antibiotics to combat bacterial infections, often followed by an application of non-native probiotics advertised to ease the impact of antibiotic-induced gut dysbiosis. We tested whether probiotics affect the gut microbiome or disease prevalence, or rescue the negative effects of antibiotic induced gut dysbiosis. We found no difference in the gut microbiome or disease markers by probiotic application or antibiotic recovery associated with probiotic treatment. A colony-level application of the antibiotics oxytetracycline and tylosin produced an immediate decrease in gut microbiome size, and over the longer-term, very different and persistent dysbiotic effects on the composition and membership of the hindgut microbiome. Our results demonstrate the lack of probiotic effect or antibiotic rescue, detail the duration and character of dysbiotic states resulting from different antibiotics, and highlight the importance of the gut microbiome for honeybee health.

IntroductionLes produits de tabac chauffé sont de nouveaux produits du tabac susceptibles d’attirer les jeunes. Cette étude visait à explorer, dans quatre provinces canadiennes, si la proximité et la densité des détaillants de produits de tabac chauffé autour des écoles secondaires étaient associées à une utilisation de ces produits chez les adolescents. MéthodologieUne recherche menée en ligne entre novembre 2020 et mars 2021 a permis de repérer les détaillants qui vendaient des dispositifs IQOS et des bâtonnets HEETS (conçus pour les dispositifs IQOS) dans des zones tampons circulaires de 500 m, 1 000 m et 1 500 m autour de 120 écoles secondaires ayant participé à l’étude COMPASS 2020-2021. Les données sur la proximité et la densité des détaillants ont été liées à des données transversales sur les élèves (N = 40 636), et des modèles de régression multiniveaux ont été utilisés pour explorer l’association entre, d’une part, la proximité et la densité des détaillants de produits de tabac chauffé et, d’autre part, l’utilisation de produits de tabac chauffé, après ajustement pour les covariables pertinentes. RésultatsSi seulement 10,0 % des écoles étaient situées à moins de 1 000 m d’au moins un détaillant vendant des dispositifs IQOS, 65,0 % d’entre elles étaient situées à proximité d’au moins un détaillant vendant des bâtonnets HEETS. L’école fréquentée par l’élève était responsable de 23,7 % de la variabilité de la probabilité d’utilisation de produits de tabac chauffé. Toutefois, la proximité et la densité des détaillants de produits de tabac chauffé autour des écoles n’ont présenté aucune association significative avec la probabilité d’utilisation de ces produits chez les élèves. ConclusionBien que l’école fréquentée par l’élève soit responsable d’une part importante de la variabilité de l’utilisation de produits de tabac chauffé, ces résultats laissent penser que les élèves pourraient obtenir des produits de tabac chauffé par des sources autres que les commerces de détail. Il faut continuer de surveiller la situation, car l’utilisation des produits de tabac chauffé chez les adolescents est susceptible d’évoluer.

IntroductionHeated tobacco products (HTPs) are novel tobacco products that may appeal to youth. This study explored whether HTP retailer proximity and density to secondary schools were associated with youth use of HTPs in four Canadian provinces. MethodsAn online search between November 2020 and March 2021 identified retailers selling IQOS devices and HEETS (tobacco sticks used in IQOS) within 500 m, 1000 m and 1500 m radius circular buffer zones around high schools (N = 120) participating in the COMPASS study in 2020–2021. Retailer proximity/density data were linked to crosssectional student-level data (N = 40 636 students), and multilevel regression models examined the association between HTP retailer proximity and density and current HTP use, controlling for relevant covariates. ResultsWhile only 10.0% of schools had at least one retailer selling IQOS devices within 1000 m of the school, 65.0% of schools had at least one retailer selling HEETS. The school a student attended accounted for 23.7% of the variability in the likelihood of currently using an HTP. However, HTP retailer proximity to and density around schools were not significantly associated with the likelihood of students currently using HTPs. ConclusionWhile the school a student attended accounted for a significant amount of variability in HTP use, these findings suggest that students may be obtaining HTPs through other, non-retail sources. Continued monitoring is warranted as HTP use among youth may change.

Abstract Maternal obesity increases the risk of childhood obesity and programs the offspring to develop metabolic syndrome later in their life. Palmitate is the predominant saturated free fatty acid (FFA) that is transported across the placenta to the fetus. We have recently shown that saturated FFA in the maternal circulation as a result of increased adipose tissue lipolysis in third trimester of pregnancy induces trophoblast lipoapoptosis. Here, we hypothesized that palmitate induces integrated stress response by activating mitogen-activated protein kinases (MAPKs), endoplasmic reticulum (ER) stress and granular stress and lipoapoptosis in trophoblasts. Choriocarcinoma-derived third-trimester placental trophoblast-like cells (JEG-3 and JAR) referred as trophoblasts were exposed to various concentrations of palmitate (PA). Apoptosis was assessed by nuclear morphological changes and caspase 3/7 activity. Immunoblot and immunofluorescence analysis was performed to measure the activation of MAPKs, ER stress and granular stress response pathways. Trophoblasts exposed to pathophysiological concentrations of PA showed a concentration-dependent increase in trophoblast lipoapoptosis. PA induces a caspase-dependent trophoblast lipoapoptosis. Further, PA induces MAPK activation (JNK and ERK) via phosphorylation, and activation of ER stress as evidenced by an increased phosphorylation eIF2α & IRE1α. PA also induces the activation of stress granules formation. Two pro-apoptotic transcriptional mediators of PA-induced trophoblast lipoapoptosis, CHOP and FoxO3 have increased nuclear translocation. Mechanistically, PA-induced JNK is critical for trophoblast lipoapoptosis. However, PA-induced activation of ERK and stress granule formation were shown to be cell survival signals to combat subcellular stress due to PA exposure. In conclusion, PA induces the activation of integrated stress responses, among which small molecule inhibition of JNK demonstrated that activation of JNK is critical for PA-induced trophoblast lipoapoptosis and small molecule activation of stress granule formation significantly prevents PA-induced trophoblast lipoapoptosis.

Este artigo tem como objetivo discutir o trabalho do professor de língua inglesa (doravante LI) com base no Interacionismo Sociodiscursivo (ISD) e no marxismo, a partir de recortes de duas pesquisas em nível de doutorado do Programa de Estudos da Linguagem da Universidade Estadual de Londrina e vinculados ao grupo de pesquisa Linguagem e Educação (LED). Ele traz uma reflexão sobre o significado das prescrições no trabalho do professor formador e do professor da educação básica na rede pública e a função que elas ocupam neste contexto, a partir da investigação sobre o material/livro didático selecionado/produzido por professores formadores de professores de LI e dos manuais do professor (MP) de coleções didáticas de LI, aprovados nas avaliações do Programa Nacional do Livro Didático (PNLD) dos anos 2011 e 2014. A discussão desenvolvida neste artigo permite constatar que, as prescrições e autoprescrições que fazem parte do dia a dia do professor podem ser fator gerador de desenvolvimento, contudo, as condições cada vez mais precárias do trabalho docente, nos diversos níveis de ensino, resultam na sobrecarga de trabalho, na desvalorização do professor, podendo tornar os esforços na formação e nas políticas públicas, como é o caso do PNLD e da adoção de livro didático, inócuos

Abstract Background The value of a life is regularly monetised by government departments for informing resource allocation. Guidance documents indicate how economic evaluation should be conducted, often specifying precise values for different impacts. However, we find different values of life and health are used in analyses by departments within the same government despite commonality in desired outcomes. This creates potential inconsistencies in considering trade-offs within a broader public sector spending budget. We provide evidence to better inform the political process and to raise important issues in assessing the value of public expenditure across different sectors. Methods Our document analysis identifies thresholds, explicitly or implicitly, as observed in government-related publications in the following public sectors: health, social care, transport, and environment. We include both demand-side and supply-side thresholds, understood as societies’ and governments’ willingness to pay for health gains. We look at key countries that introduced formal economic evaluation processes early on and have impacted other countries’ policy development: Australia, Canada, Japan, New Zealand, the Netherlands, and the United Kingdom. We also present a framework to consider how governments allocate resources across different public services. Results Our analysis supports that identifying and describing the Value of a Life from disparate public sector activities in a manner that facilitates comparison is theoretically meaningful. The optimal allocation of resources across sectors depends on the relative position of benefits across different attributes, weighted by the social value that society puts on them. The value of a Quality-Adjusted Life Year is generally used as a demand-side threshold by Departments of transport and environment. It exceeds those used in health, often by a large enough proportion to be a multiple thereof. Decisions made across departments are generally based on an unspecified rationing rule. Conclusions Comparing government expenditure across different public sector departments, in terms of the value of each department outcome, is not only possible but also desirable. It is essential for an optimal resource allocation to identify the relevant social attributes and to quantify the value of these attributes for each department.

Water is one of Earth's fundamental natural systems. It is crucial to foster water literacy in today's global citizens, particularly through formal education. The purpose of this research, in parallel with a study focused on human dimensions of water systems (Mostacedo-Marasovic et al., in press), is to examine water-related K-12 standards for teaching and learning about water and natural systems and develop a comprehensive and transdisciplinary perspective on water education. Our overarching question is, "What do disciplinary standards specify as outcomes for students' learning about water and natural systems?" Our research questions are: (1) "To what extent do these water-related standards address recognized domains of learning?" and (2) "What thematic outcomes for students' learning are apparent across grades in these water-related standards?." We use chi-square statistics and conventional qualitative content analysis complemented by processes from grounded theory to analyze water-related education standards (N = 196) from 11 education-oriented governmental and non-governmental organizations based in the United States and the United Nations. Our results indicate that, first, water-related standards emphasize the cognitive domain, including declarative and procedural knowledge, for water-related concepts and skills. The affective domain and its social component are far less prevalent. Second, the water-related standards illustrate four categories including abundance, distribution, and movement of water on Earth; water and the Geosphere; water and climate; and water and life. These findings provide a more comprehensive perspective from multiple disciplines of the natural sciences on outcomes for teaching and learning about water and natural systems, as well as the learning domains they address. These can inform educational efforts to cultivate water literacy across K-12 through teaching and learning.

Background: Familiarity breeds complacency. One case of sore throat can start to sound like another. However, even common viral and bacterial infections can lead to serious sequelae. Clinicians cannot make a diagnosis if they do not consider it in their differential. Case: The presentation -- and subsequent hospitalization -- of a septic 19 year-old male college student is described. Despite brief interval improvement, he became hypoxic one week after developing a sore throat and was ultimately diagnosed with Lemierre's syndrome (septic thrombophlebitis of the internal jugular vein) via blood cultures and advanced imaging. Conclusions: Though rare, Lemierre's syndrome carries a high mortality rate. It should be considered an emergent complication of head and neck infections, particularly in young adults.

Since taking office, the Biden administration has sought to advance a complex and ambitious higher education regulatory agenda. The U.S. Department of Education held two separate rounds of negotiated rulemaking in 2021-22 to rewrite rules governing student loan relief programs and institutional accountability. This fall, the agency announced plans to convene a negotiated rulemaking committee to draft a new pathway to student debt relief and is also poised to launch another major round of rulemaking focused on accreditation, distance education, state authorization, third-party servicers, and a number of other topics. The latest moves suggest that the White House and department plan to move aggressively to continue to influence postsecondary education in the second half of President Biden's term. However, limited resources and competing priorities could impact the Department of Education's ability to finalize and implement the entire slate of potential new rules ahead of next year's presidential election. This articles provides an update on: (1) student loan and institutional accountability rules; (2) student loan debt relief rules; and (3) institutional quality and accountability rules.

Leaders are needed to address the agriculture industry's increasingly complex and interconnected problems. Colleges of agriculture who offer leadership development coursework and degree programs often support student organizations to provide critical everyday opportunities for students to practice leadership in an authentic environment. This qualitative case study examined undergraduate students' perceptions of, and experience with, leadership in student organizations in one Midwestern college of agriculture. Results indicated that students participated in student organizations to find students with similar interests, connect with potential employers, and improve their own employability. Results also indicated that leadership was typically conflated with position, and that industrial approaches to leadership were most common. This study has implications for administrators and faculty responsible for advising student organizations, and, more broadly, for leadership development programs in colleges of agriculture.

The increasing interest in computer science (CS) and CS-integrated STEM teaching and learning has created a need for assessment instruments that can be used to evaluate the efficacy of innovative instructional approaches to K-12 CS education. However, there is a lack of validated assessment tools aligned to core CS concepts for younger students. This paper reports on the development and validation of a CS concept assessment for middle grades (ages 11-13) students. A total of 27 multiple-choice items were developed, guided by focal knowledge, skills and abilities associated with the concepts of variables, loops, conditionals, and algorithms. These items were administered to 457 middle grades students. The items were presented in form of block-based programming code and administered in a week-long computational modeling intervention. A combination of classical test theory and item response theory approaches were used to validate the assessment. Based on results, it was found that only 24 items are considered valid and reliable items to measure CS conceptual understanding. The results also suggested that the assessment can be used as a pre and post-test to investigate students' learning gains. This work fills an important gap by providing a key resource for researchers and practitioners interested in assessing middle grades student CS conceptual understanding.

Background. Advocates argue that end-of-life (EOL) care is systematically disadvantaged by the quality-adjusted life-year (QALY) framework. By definition, EOL care is short duration and not primarily intended to extend survival; therefore, it may be inappropriate to value a time element. The QALY also neglects nonhealth dimensions such as dignity, control, and family relations, which may be more important at EOL. Together, these suggest the QALY may be a flawed measure of the value of EOL care. To test these arguments, we administered a stated preference survey in a UK-representative public sample. Methods. We designed a discrete choice experiment (DCE) to understand public preferences over different EOL scenarios, focusing on the relative importance of survival, conventional health dimensions (especially physical symptoms and anxiety), and nonhealth dimensions such as family relations, dignity, and sense of control. We used latent class analysis to understand preference heterogeneity. Results. A 4-class latent class multinomial logit model had the best fit and illustrated important heterogeneity. A small class of respondents strongly prioritized survival, whereas most respondents gave relatively little weight to survival and, generally speaking, prioritized nonhealth aspects. Conclusions. This DCE illustrates important heterogeneity in preferences within UK respondents. Despite some preferences for core elements of the QALY, we suggest that most respondents favored what has been called “a good death” over maximizing survival and find that respondents tended to prioritize nonhealth over conventional health aspects of quality. Together, this appears to support arguments that the QALY is a poor measure of the value of EOL care. We recommend moving away from health-related quality of life and toward a more holistic perspective on well-being in assessing EOL and other interventions. Highlights Advocates argue that some interventions, including but not limited to end-of-life (EOL) care, are valued by patients and the public but are systematically disadvantaged by the quality-adjusted life-year (QALY) framework, leading to an unfair and inefficient allocation of health care resources. Using a discrete choice experiment, we find some support for this argument. Only a small proportion of public respondents prioritized survival in EOL scenarios, and most prioritized nonhealth aspects such as dignity and family relations. Together, these results suggest that the QALY may be a poor measure of the value of EOL care, as it neglects nonhealth aspects of quality and well-being that appear to be important to people in hypothetical EOL scenarios.

Abstract Terminal drought is one of the major constraints to crop production in chickpea (Cicer arietinum L.). In order to map drought tolerance related traits at high resolution, we sequenced multi‐parent advanced generation intercross (MAGIC) population using whole genome resequencing approach and phenotyped it under drought stress environments for two consecutive years (2013–14 and 2014–15). A total of 52.02 billion clean reads containing 4.67 TB clean data were generated on the 1136 MAGIC lines and eight parental lines. Alignment of clean data on to the reference genome enabled identification of a total, 932,172 of SNPs, 35,973 insertions, and 35,726 deletions among the parental lines. A high‐density genetic map was constructed using 57,180 SNPs spanning a map distance of 1606.69 cM. Using compressed mixed linear model, genome‐wide association study (GWAS) enabled us to identify 737 markers significantly associated with days to 50% flowering, days to maturity, plant height, 100 seed weight, biomass, and harvest index. In addition to the GWAS approach, an identity‐by‐descent (IBD)‐based mixed model approach was used to map quantitative trait loci (QTLs). The IBD‐based mixed model approach detected major QTLs that were comparable to those from the GWAS analysis as well as some exclusive QTLs with smaller effects. The candidate genes like FRIGIDA and CaTIFY4b can be used for enhancing drought tolerance in chickpea. The genomic resources, genetic map, marker‐trait associations, and QTLs identified in the study are valuable resources for the chickpea community for developing climate resilient chickpeas.

IntroductionPancreatic islet isolation is essential for studying islet physiology, pathology, and transplantation, and feline islets could be an important model for human type II diabetes mellitus (T2D). Traditional isolation methods utilizing collagenases inflict damage and, in cats, may contribute to the difficulty in generating functional islets, as demonstrated by glucose-stimulated insulin secretion (GSIS). GLUT2 expression in β cells may allow for adaptation to hyperosmolar glucose solutions while exocrine tissue is selectively disrupted.MethodsHere we developed a protocol for selective osmotic shock (SOS) for feline islet isolation and evaluated the effect of different hyperosmolar glucose concentrations (300 mmol/L and 600 mmol/L) and incubation times (20 min and 40 min) on purity, morphology, yield, and GSIS.ResultsAcross protocol treatments, islet yield was moderate and morphology excellent. The treatment of 600 mmol/L glucose solution with 20 min incubation resulted in the highest stimulation index by GSIS.DiscussionGlucose responsiveness was demonstrated, permitting future in vitro studies. This research opens avenues for understanding feline islet function and transplantation possibilities and enables an additional islet model for T2D.

In Fall 2022, the U.S. Education Department unveiled a drastic overhaul of federal student loan policies. The new rules serve as a key vehicle to advance the Biden administration's higher education agenda. However, some of the final regulations look quite different from the policy proposals initially outlined in President Joe Biden's campaign platform and early presidency. Biden campaigned on bold plans to expand higher education access and affordability, provide broader debt relief for student loan borrowers, and to strengthen institutional accountability measures. Shortly after taking office, President Biden signed a series of executive directives and sent to Congress a pair of expansive legislative proposals highlighting the administration's immediate priorities.

This exploratory paper highlights how problem-based learning (PBL) provided the pedagogical framework used to design and interpret learning analytics from "Crystal Island: EcoJourneys," a collaborative game-based learning environment centred on supporting science inquiry. In "Crystal Island: EcoJourneys," students work in teams of four, investigate the problem individually and then utilize a brainstorming board, an in-game PBL whiteboard that structured the collaborative inquiry process. The paper addresses a central question: how can PBL support the interpretation of the observed patterns in individual actions and collaborative interactions in the collaborative game-based learning environment? Drawing on a mixed method approach, we first analyzed students' pre- and post-test results to determine if there were learning gains. We then used principal component analysis (PCA) to describe the patterns in game interaction data and clustered students based on the PCA. Based on the pre- and post-test results and PCA clusters, we used interaction analysis to understand how collaborative interactions unfolded across selected groups. Results showed that students learned the targeted content after engaging with the game-based learning environment. Clusters based on the PCA revealed four main ways of engaging in the game-based learning environment: students engaged in low to moderate self-directed actions with: (1) high and (2) moderate collaborative sense-making actions; (3) low self-directed with low collaborative sense-making actions; and (4) high self-directed actions with low collaborative sense-making actions. Qualitative interaction analysis revealed that a key difference among four groups in each cluster was the nature of verbal student discourse: students in the low to moderate self-directed and high collaborative sense-making cluster actively initiated discussions and integrated information they learned to the problem, whereas students in the other clusters required more support. These findings have implications for designing adaptive support that responds to students' interactions with in-game activities.

Abstract Background Dominance and other non-additive genetic effects arise from the interaction between alleles, and historically these phenomena play a major role in quantitative genetics. However, most genome-wide association studies (GWAS) assume alleles act additively. Results We systematically investigate both dominance—here representing any non-additive within-locus interaction—and additivity across 574 physiological and gene expression traits in three mammalian stocks: F2 intercross pigs, rat heterogeneous stock, and mice heterogeneous stock. Dominance accounts for about one quarter of heritable variance across all physiological traits in all species. Hematological and immunological traits exhibit the highest dominance variance, possibly reflecting balancing selection in response to pathogens. Although most quantitative trait loci (QTLs) are detectable as additive QTLs, we identify 154, 64, and 62 novel dominance QTLs in pigs, rats, and mice respectively that are undetectable as additive QTLs. Similarly, even though most cis-acting expression QTLs are additive, gene expression exhibits a large fraction of dominance variance, and trans-acting eQTLs are enriched for dominance. Genes causal for dominance physiological QTLs are less likely to be physically linked to their QTLs but instead act via trans-acting dominance eQTLs. In addition, thousands of eQTLs are associated with alternatively spliced isoforms with complex additive and dominant architectures in heterogeneous stock rats, suggesting a possible mechanism for dominance. Conclusions Although heritability is predominantly additive, many mammalian genetic effects are dominant and likely arise through distinct mechanisms. It is therefore advantageous to consider both additive and dominance effects in GWAS to improve power and uncover causality.

High-resolution (< 1 km) atmospheric modeling is increasingly used to study precipitation distributions in complex terrain and cryosphere–atmospheric processes. While this approach has yielded insightful results, studies over annual timescales or at the spatial extents of watersheds remain unrealistic due to the computational costs of running most atmospheric models. In this paper we introduce a high-resolution variant of the Intermediate Complexity Atmospheric Research (ICAR) model, HICAR. We detail the model development that enabled HICAR simulations at the hectometer scale, including changes to the advection scheme and the wind solver. The latter uses near-surface terrain parameters which allow HICAR to simulate complex topographic flow features. These model improvements clearly influence precipitation distributions at the ridge scale (50 m), suggesting that HICAR can approximate processes dependent on particle–flow interactions such as preferential deposition. A 250 m HICAR simulation over most of the Swiss Alps also shows monthly precipitation patterns similar to two different gridded precipitation products which assimilate available observations. Benchmarking runs show that HICAR uses 594 times fewer computational resources than the Weather Research and Forecasting (WRF) atmospheric model. This gain in efficiency makes dynamic downscaling accessible to ecohydrological research, where downscaled data are often required at hectometer resolution for whole basins at seasonal timescales. These results motivate further development of HICAR, including refinement of parameterizations used in the wind solver and coupling of the model with an intermediate-complexity snow model.

Abstract Background Continuous glucose monitoring systems have been validated for eu‐ and hyperglycemic cats. The FreeStyle Libre 2 (FSL2) is sufficiently accurate in people during hypoglycemia to guide critical treatment decisions without confirmation of blood glucose concentration (BG). Objectives Assess FSL2 accuracy in cats with hypoglycemia. Animals Nine healthy, purpose‐bred cats. Methods Hyperinsulinemic‐hypoglycemic clamps were performed by IV infusion of regular insulin (constant rate) and glucose (variable rate). Interstitial glucose concentration (IG), measured by FSL2, was compared to BG measured by AlphaTrak2. Data were analyzed for all paired measurements (n = 364) and separately during stable BG (≤1 mg/dL/min change over 10 minutes). Pearson's r test, Bland‐Altman test, and Parkes Error Grid analysis respectively were used to determine correlation, bias, and clinical accuracy (P

Combining samples for genetic association is standard practice in human genetic analysis of complex traits, but is rarely undertaken in rodent genetics. Here, using 23 phenotypes and genotypes from two independent laboratories, we obtained a sample size of 3076 commercially available outbred mice and identified 70 loci, more than double the number of loci identified in the component studies. Fine-mapping in the combined sample reduced the number of likely causal variants, with a median reduction in set size of 51%, and indicated novel gene associations, including Pnpo, Ttll6, and GM11545 with bone mineral density, and Psmb9 with weight. However, replication at a nominal threshold of 0.05 between the two component studies was low, with less than one-third of loci identified in one study replicated in the second. In addition to overestimates in the effect size in the discovery sample (Winner's Curse), we also found that heterogeneity between studies explained the poor replication, but the contribution of these two factors varied among traits. Leveraging these observations, we integrated information about replication rates, study-specific heterogeneity, and Winner's Curse corrected estimates of power to assign variants to one of four confidence levels. Our approach addresses concerns about reproducibility and demonstrates how to obtain robust results from mapping complex traits in any genome-wide association study.