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The circumstances associated with high levels of achievement in undergraduate studies has not been thoroughly explored in the Australian context. This study investigated factors predicting high academic achievement, defined as maintaining a Distinction average, at undergraduate level. Findings revealed several factors that predicted achievement after two semesters of study. These factors included essay writing skills, with students having satisfactory writing 5.16 times more likely to maintain a Distinction average compared to those with below satisfactory writing; faculty, with students enrolled in Health Sciences 4.63 times more likely compared to students from other faculties; language background, with English-speaking background students 1.67 times more likely compared to English as an additional language or dialect (EAL/D) students; gender, with females 1.45 more likely compared to males; and age, with older students 1.03 times more likely to achieve high performance compared to younger students. Creating a profile of students likely to excel academically assists decision makers in allocating resources to students less likely to achieve. This research opens the door to further studies investigating whether these factors play a role in predicting student achievement at university.

Cannabis has demonstrated anticonvulsant properties, and about thirty percent of epileptic patients do not have satisfactory seizure management with standard treatment and could potentially benefit from cannabis-based intervention. Here, we report the use of cannabinoids to treat pentylenetetrazol (PTZ)-induced convulsions in a zebrafish model, their effect on gene expression, and a simple assay for assessing their uptake in zebrafish tissues. Using an optimized behavioral assay, we show that cannabidiol (CBD) and cannabichromene (CBC) and cannabinol (CBN) are effective at reducing seizures at low doses, with little evidence of sedation, and our novel HPLC assay indicates that CBC is effective with the lowest accumulation in larval tissues. All cannabinoids tested were effective at higher concentrations. Pharmacological manipulation of potential receptors demonstrates that Gpr55 partially mediates the anticonvulsant effects of CBD. Treatment of zebrafish larvae with endocannabinoids, such as 2-arachidonoylglycerol (2-AG) and anandamide (AEA), altered larvae movement, and the expression of genes that regulate their metabolism was affected by phytocannabinoid treatment, highlighting the possibility that changes to endocannabinoid levels may represent one facet of the anticonvulsant effect of phytocannabinoids.

Guinea pigs (Cavia porcellus) are popular pets and used as laboratory animals, however, their dietary preferences are under-studied. It is important for guinea pig owners and carers to increase the opportunity for good animal welfare by providing personalized and enriching dietary options. Thus, this study aimed to assess the use of paired-stimulus and multiple-stimulus-without-replacement preference assessments to determine the food preferences of seven male guinea pigs and test the validity of the methods by testing the demand for the most- and least preferred foods as reinforcers for climbing an elevated ramp. Generally, the preference assessments identified the same foods as the most preferred for each guinea pig, but not the least preferred foods. Guinea pigs climbed up to the steepest angle for both most and least preferred foods, but a non-linear least squares regression and demand analysis indicated faster climbing and inelastic demand for most preferred foods compared to slower climbing and elastic demand for least preferred foods. Both preference assessment methods were valid in identifying a preferred food, however, the multiple-stimulus-without-replacement assessment was more efficient to conduct. High-preference foods such as parsley and dandelion are recommended as future training reinforcers for guinea pigs and as foods to consider using as enrichment in captive guinea pig systems to encourage good welfare.

This paper explores service-learning as a mode of cultivating student stakeholders in university education. Previous studies have examined increasing student engagement through experiential learning, writing across the curriculum, and recognizing the interdisciplinarity of general education classrooms, but few have brought these elements into conversation as contexts that might foster students' sense of ownership of their education. While students are recipients of carefully planned faculty-designed curricula, this study suggests that cross-curricular programs, such as writing in the disciplines, could benefit from student input given their direct experience of writing assignments and expectations in multiple classroom environments. This study investigates, in hybrid mode (intersectional pedagogy and auto-ethnographic case study), a plan aimed at developing cross-campus knowledge about writing instruction through an inter-campus service-learning project. The featured project underscores the importance of experiential learning that enhances student estimation of writing as a mode of learning, involves students in the evaluation of campus writing curricula, and develops a sense of writing as highly valuable to university education and integral to all fields in subsequent professional lives.

Traditional principal preparation programs (PPPs) that include coursework and internship opportunities are most commonly the basis by which aspiring school leaders are prepared for future work (Dickens, et al., 2021; Grissom, Jason A., et al., 2018; Kearney & Valadez, 2015; Oliver, et al., 2018). The COVID-19 pandemic provided a challenge for aspiring school administrators, regardless of their personal dispositions or form of preparation (Fernandez & Shaw, 2020; Author & Author, 2021). Using Situational Leadership as a conceptual frame (Hersey & Blanchard, 1977), the purpose of this study was to compare perceptions by school leaders, pre- versus post-principal preparation program, who rely on a particular use of framing (Bolman & Deal, 2013) to guide their professional practice. In the spring of 2023, eight school administrators in their first three years of professional service, all of whom had been enrolled in an online principal preparation program (PPP), were interviewed to compare responses that they provided during their PPP to those expressed while serving as school administrators. In addition to the interviews, the study participants completed the Principal Self-Efficacy Survey (PSES) to indicate feelings of professional confidence. Results of this investigation showed high levels of self-efficacy among participants, especially with regard to instructional leadership, as well as a general agreement among participants regarding their use of situational framing. In addition, results showed a general increase in professional maturity, pre- to post-PPP, gleaned from self-reports about relationships and tasks in the workplace.

Background: Rural populations in the USA demonstrate a high degree of vaccine hesitancy, particularly surrounding COVID-19 vaccines. Objectives: Following the successful implementation of a COVID-19 vaccination campaign with a rural-based health system in New York state, the goal of this project was to develop a large community-academic partnership with multiple rural-based community organisations to implement an additional COVID-19 vaccination campaign tailored to rural audiences. Methods: Campaign materials were created and refined with several collaborators across multiple ruralbased hospitals, health centres and community organisations. Campaign effectiveness was examined through an analysis of New York state vaccination data. Lessons learned: This project shows that larger community-academic partnerships involving multiple organisations can be achieved and utilised to address complex public health issues such as vaccine hesitancy. Conclusions: Larger and longer-term community-academic partnerships can be leveraged to combat a wide range of public health issues and enable a personalised focus on specific communities.

Sociology plays a key role in empathy development, which is central to addressing complex social problems. However, little is known about what types of courses work best to enhance empathy. In parallel, sociological animal studies (SAS) has evolved as a relatively new subfield focused on assessing human and animal relationships. SAS research suggests that our interactions with animals enhance empathy development. Combining these literatures, we assess if SAS compared to non-SAS courses impact affective and cognitive empathy for humans and animals differently. Findings reveal that students who take SAS courses demonstrate greater postcourse human and animal empathy even when controlling for precourse levels of empathy and other factors that drive empathy development. Although SAS remains on the periphery of the discipline, this study suggests that it should be a central component of the sociological curriculum.

Trauma in early childhood is a significant public health concern. Early childhood education and care (ECEC) services play a critical role in identifying and responding to children impacted by trauma. However, little is known about early childhood professionals' experiences and needs relating to supporting trauma-impacted children. The aim of this qualitative study was to explore early childhood professionals' experiences of working with trauma-impacted children in ECEC, the barriers to adopting trauma-informed approaches, and the organisation-wide shift that is needed to embed them. Semi-structured interviews were conducted with 22 early childhood educators, organisational leaders, and childhood trauma consultants in Victoria, Australia. Thematic analyses revealed that early childhood professionals' perceived increasing prevalence of trauma in children attending ECEC. However, educators are generally unprepared and unsupported for this, and experience many workplace challenges leaving them feeling overwhelmed. This highlighted the need to support the professional development and well-being of early childhood educators. Meanwhile, the study identified systemic barriers impeding the implementation of trauma-informed approaches within ECEC. The findings also suggest that the collective efforts "starting from the top", with everyone engaged, coupled with cross-sector collaboration is needed for meaningful, trauma-informed organisational change within ECEC.

This paper reports the findings of a Canada based multi-institutional study designed to investigate the relationships between admissions criteria, in-program assessments, and performance on licensing exams. The study's objective is to provide valuable insights for improving educational practices across different institutions. Data were gathered from six medical schools: McMaster University, the Northern Ontario School of Medicine University, Queen's University, University of Ottawa, University of Toronto, and Western University. The dataset includes graduates who undertook the Medical Council of Canada Qualifying Examination Part 1 (MCCQE1) between 2015 and 2017. The data were categorized into five distinct sections: demographic information as well as four matrices: admissions, course performance, objective structured clinical examination (OSCE), and clerkship performance. Common and unique variables were identified through an extensive consensus-building process. Hierarchical linear regression and a manual stepwise variable selection approach were used for analysis. Analyses were performed on data set encompassing graduates of all six medical schools as well as on individual data sets from each school. For the combined data set the final model estimated 32% of the variance in performance on licensing exams, highlighting variables such as Age at Admission, Sex, Biomedical Knowledge, the first post-clerkship OSCE, and a clerkship theta score. Individual school analysis explained 41-60% of the variance in MCCQE1 outcomes, with comparable variables to the analysis from of the combined data set identified as significant independent variables. Therefore, strongly emphasising the need for variety of high-quality assessment on the educational continuum. This study underscores the importance of sharing data to enable educational insights. This study also had its challenges when it came to the access and aggregation of data. As such we advocate for the establishment of a common framework for multi-institutional educational research, facilitating studies and evaluations across diverse institutions. This study demonstrates the scientific potential of collaborative data analysis in enhancing educational outcomes. It offers a deeper understanding of the factors influencing performance on licensure exams and emphasizes the need for addressing data gaps to advance multi-institutional research for educational improvements.

This article focuses on screening the major secreted proteins by the ischemia-challenged cardiac stromal fibroblasts (CF), the assessment of their expression status and functional role in the post-ischemic left ventricle (LV) and in the ischemia-challenged CF culture and to phenotype CF at single cell resolution based on the positivity of the identified mediators. The expression level of CRSP2, HSP27, IL-8, Cofilin-1, and HSP90 in the LV tissues following coronary artery bypass graft (CABG) and myocardial infarction (MI) and CF cells followed the screening profile derived from the MS/MS findings. The histology data unveiled ECM disorganization, inflammation and fibrosis reflecting the ischemic pathology. CRSP2, HSP27, and HSP90 were significantly upregulated in the LV-CABG tissues with a concomitant reduction ion LV-MI whereas Cofilin-1, IL8, Nrf2, and Troponin I were downregulated in LV-CABG and increased in LV-MI. Similar trends were exhibited by ischemic CF. Single cell transcriptomics revealed multiple sub-phenotypes of CF based on their respective upregulation of CRSP2, HSP27, IL-8, Cofilin-1, HSP90, Troponin I and Nrf2 unveiling pathological and pro-healing phenotypes. Further investigations regarding the underlying signaling mechanisms and validation of sub-populations would offer novel translational avenues for the management of cardiac diseases.

Introduction: The United States lacks a national interfacility patient transfer coordination system. During the coronavirus 2019 (COVID-19) pandemic, many hospitals were overwhelmed and faced difficulties transferring sick patients, leading some states and cities to form transfer centers intended to assist sending facilities. In this study we aimed to explore clinician experiences with newly implemented transfer coordination centers.Methods: This mixed-methods study used a brief national survey along with in-depth interviews. The American College of Emergency Physicians Emergency Medicine Practice Research Network (EMPRN) administered the national survey in March 2021. From September–December 2021, semi-structured qualitative interviews were conducted with administrators and rural emergency clinicians in Arizona and New Mexico, two states that started transfer centers during COVID-19.Results: Among 141 respondents (of 765, 18.4% response rate) to the national EMPRN survey, only 30% reported implementation or expansion of a transfer coordination center during COVID-19. Those with new transfer centers reported no change in difficulty of patient transfers during COVID-19 while those without had increased difficulty. The 17 qualitative interviews expanded upon this, revealing four major themes: 1) limited resources for facilitating transfers even before COVID-19; 2) increased number of and distance to transfer partners during the COVID-19 pandemic; 3) generally positive impacts of transfer centers on workflow, and 4) the potential for continued use of centers to facilitate transfers.Conclusion: Transfer centers may have offset pandemic-related transfer challenges brought on by the COVID-19 pandemic. Clinicians who frequently need to transfer patients may particularly benefit from ongoing access to such transfer coordination services.

Oxytocin (OXT) is a peptide hormone and a neuropeptide that regulates various peripheral physiological processes and modulates behavioral responses in the central nervous system. While the humoral release occurs from the axons arriving at the median eminence, the neuropeptide is also released from oxytocinergic cell axons in various brain structures that contain its receptor, and from their dendrites in hypothalamic nuclei and potentially into the cerebrospinal fluid (CSF). Understanding oxytocins complex functions requires the knowledge on patterns of oxytocinergic projections in relationship to its receptor (OXTR). This study provides the first comprehensive examination of the oxytocinergic system in the prairie vole (Microtus ochrogaster), an animal exhibiting social behaviors that mirror human social behaviors linked to oxytocinergic functioning. Using light and electron microscopy, we characterized the neuroanatomy of the oxytocinergic system in this species. OXT+ cell bodies were found primarily in the hypothalamus, and axons were densest in subcortical regions. Examination of the OXT+ fibers and their relationship to oxytocin receptor transcripts (Oxtr) revealed that except for some subcortical structures, the presence of axons was not correlated with the amount of Oxtr across the brain. Of particular interest, the cerebral cortex that had high expression of Oxtr transcripts contained little to no fibers. Electron microscopy is used to quantify dense cored vesicles (DCV) in OXT+ axons and to identify potential axonal release sites. The ependymal cells that line the ventricles were frequently permissive of DCV-containing OXT+ dendrites reaching the third ventricle. Our results highlight a mechanism in which oxytocin is released directly into the ventricles and circulates throughout the ventricular system, may serve as the primary source for oxytocin that binds to OXTR in the cerebral cortex.

Environmental indicators for nitrogen (N) use efficiency (NUE) based only on N inputs and N removal are becoming widely used in science, policy, and commercial supply chains to track the sustainability of food production. However, these indicators do not reflect the contribution of inherent soil productivity, which can supply half of crop demand and is therefore a core principle in determining how much fertilizer is needed and the corresponding risk of N losses. Using a global dataset of optimal N rates for crop production, we evaluated the performance of conventional (N recovery efficiency) and simplified NUE indicators to understand their relationship and respective limitations, helping inform policy efforts for simultaneously meeting food production and sustainability goals. A key finding is that conventional agronomic approaches designed to optimize crop productivity and profit related to N fertilizer inputs have tradeoffs for environmental performance, with only 35 and 31 % of observations (n=448) falling within sustainable ranges for NUE. Meanwhile, simplified NUE indicators such as N balance or the ratio of N outputs to inputs were unable to detect sites with inherently low N recovery efficiency and high risk of N losses, highlighting a weakness of neglecting soil N supply in their calculations. Together these results suggest the need for a combined approach that merges insights from locally available agronomic data on N recovery efficiency with global environmental thresholds for NUE. Using our findings as a case study, we propose new steps forward for evaluating NUE in different cropping systems and regions to enhance food security while mitigating N pollution.

Fishing gear-based landings or survey methods are often used to make assessments of species stock abundance. In order to convert catch into abundance values, estimates or assumptions are made on the catch efficiency of the gear-based method. This is the case in areas where flat oysters, Ostrea edulis, are surveyed for fisheries and conservation objectives in a range of projects across Europe. Flat oyster dredge efficiency assumptions vary widely from 5–30% in published studies and uncertainty in what is an appropriate efficiency estimate has led some survey teams to switch to Catch-per-unit-effort (CPUE), where CPUE is also of concern should catch efficiency change with shellfish density, ground type or some other unmeasured variable such as shellfish distribution. We undertook an experimental approach to estimate dredge efficiency in a standard ladder dredge used to harvest and survey adult flat oysters in the UK and Ireland. The dredge efficiency trials assessed how efficiency was influenced by oyster density (between 1 and 2.2 oysters m2), distribution (clumped vs uniform) and ground types across a gradient of more hard to more soft surface sediments. Dredge efficiency was significantly affected by oyster distribution, but also density and ground hardness as well as their interactions. While a median value between 7 and 10% seems an appropriate universal ladder dredge efficiency to adopt, ground type and distribution had such an effect that local conditions may effect this considerably. Catch efficiency was negatively density-dependent, this makes CPUE methods challenging where oyster densities are likely to vary. Practitioners, regulators and researchers conducting surveys can improve CPUE approaches through standard techniques and knowledge of how catch efficiency varies as we have presented here.

The European flat oyster, Ostrea edulis, is a habitat-forming bivalve which was historically widespread throughout Europe. Following its decline due to overfishing, pollution, sedimentation, invasive species, and disease, O. edulis and its beds are now listed as a threatened and/or declining species and habitat by OSPAR. Increasing recognition of the plight of the oyster, alongside rapidly developing restoration techniques and growing interest in marine restoration, has resulted in a recent and rapid growth in habitat restoration efforts. O. edulis seed supply is currently a major bottleneck in scaling up habitat restoration efforts in Europe. O. edulis has been cultured for centuries, however, research into its culture declined following the introduction of the Pacific oyster, Crassostrea gigas to Europe in the early 1970 s. Recent efforts to renew both hatchery and pond production of O. edulis seed for habitat restoration purposes are hampered by restoration project timelines and funding typically being short, or projects not planning appropriately for the timescales required for investment, research-and-development and delivery of oyster seed by commercial producers. Furthermore, funding for restoration is intermittent, making long-term commitments between producers and restoration practitioners difficult. Long-term, strategic investment in research and production are needed to overcome these bottlenecks and meet current ambitious restoration targets across Europe.

OBJECTIVE: We outline the development of a narrative intervention guided by the Common-Sense Model of Self-Regulation (CSM) to promote Human Papillomavirus (HPV) vaccination in a diverse college population. METHODS: We adapted the Obesity-Related Behavioral Intervention Trials (ORBIT) model to guide the development, evaluation, and refinement of a CSM-guided narrative video. First, content experts developed a video script containing information on HPV, HPV vaccines, and HPV-related cancers. The script and video contents were evaluated and refined, in succession, utilizing the think-aloud method, open-ended questions, and a brief survey during one-on-one interviews with university students. RESULTS: Script and video content analyses led to significant revisions that enhanced quality, informativeness, and relevance to the participants. We highlight the critical issues that were revealed and revised in the iterative process. CONCLUSIONS: We developed and refined a CSM guided narrative video for diverse university students. This framework serves as a guide for developing health communication interventions for other populations and health behaviors. INNOVATION: This project is the first to apply the ORBIT framework to HPV vaccination and describe a process to develop, evaluate, and refine comparable CSM guided narrative interventions that are tailored to specific audiences.

People with autism spectrum conditions (ASC) have difficulties mentally simulating events, perhaps due to a difficulty mentally generating and maintaining a coherent spatial scene -- that is, 'scene construction'. The current study compared scene construction ability between autistic adults (N = 55) and age-, gender- and Intelligence Quotient-matched neurotypical adults (N = 63), using a task in which participants were asked to vividly imagine and describe fictitious scenes. Results showed that scene construction was diminished in autistic compared to neurotypical participants and was negatively associated with autistic traits. ASC diagnosis did not influence the frequency of self-reference or sensory experiences, which followed the same pattern in both groups: sight was referenced more than sound, sound was referenced more than both touch and smell, which were both referenced more than taste. Exploratory analysis of some of the cognitive predictors revealed that scene construction ability was associated with individual differences in Theory of Mind and alexithymia.

Language development can be framed as the process of learning how to mean (Halliday, 1975). From this perspective, the role of communicative function is central to the language-learning process with development being guided by interaction with experienced others. In the current study, we present a detailed analysis of the communicative functions used in interaction with prelinguistic infants aged 10-12 months from three cultural groups living in the United Kingdom. The findings indicate that caregivers from all three groups used a wide range of communicative acts when interacting with their infants, ranging from directives to discussions of inner thoughts and feelings. In addition, we identified significant differences in the frequency with which different communicative acts were used across our three groups. The study complements the positive contributions made by pivotal studies on language socialisation by highlighting the diversity and variation of caregiver speech at the functional level.

In the course of the COVID-19 pandemic, education policy debates have thrust a heightened focus on the provision of adequate school resources and on educator well-being and turnover, concerns particularly critical for school districts that serve large shares of economically disadvantaged students. In this article, we investigate voter and parent support for school spending initiatives in Missouri by analyzing data from two representative statewide surveys, one of the state's voters and one of the state's parents, focusing on total school spending and spending on teacher salaries. Missouri presents an especially salient setting in which to examine issues of equity in school spending, with below-average school spending and bottom-decile average teacher salaries. In this context, we investigate longstanding predictors of school spending support, including political ideology, alongside new hypotheses, including those pertaining to regional spending inequality and differences between voter and parent constituencies. While political ideology predicted school spending and teacher salary preferences, it did so more strongly for voters than for parents, an important consideration amid heightened political tensions in policy debates. Parent preferences, on the other hand, were more likely to be predicted by opinions of local and statewide school quality. Both voters and parents indicated sensitivity to regional spending inequality with respect to total school spending but not with respect to teacher salaries. Collectively, these findings may inform policymaking efforts in Missouri and similar prevailingly conservative contexts to use constituent preferences to guide legislative efforts.

Encouraging children to become 'good citizens' who positively contribute towards society through charitable and philanthropic action as part of their civic participation has become a core focus of policy and practice. Yet the opportunities afforded to children for active civic learning within primary education remain under-researched. This article presents findings from a multi-survey study that seeks to unpick 'what' and 'how' active civic learning is happening in primary schools across England. By mapping active civic learning across the country, we find that these opportunities are unequally dispersed. Specifically, from an early age, children from more affluent backgrounds are more likely to be prepared for active civic engagement, orientated around ideas of social justice, than those from disadvantaged backgrounds. This raises significant challenges for education policy and practice and calls for greater attention to be paid to civic learning for all children in early and middle childhood.

Early Childhood Education and Care (ECEC) services are critical points of intervention for children impacted by trauma. Intervention Mapping was utilised to develop an initiative for trauma-informed organisational change in ECEC. This paper describes how the research team understood the need and opportunity for the program using Intervention Mapping Step 1. This included: (i) convening a planning group, (ii) conducting needs assessment, (iii) describing the context for intervention, and (iv) establishing program goals. Benefits, challenges, and recommendations on using Intervention Mapping for program development in ECEC settings are discussed.

In Victoria, Australia, senior secondary mathematics students are expected to use technology and thus need to make decisions about using pen-and-paper (P&P) or technology when solving mathematics problems. The predominant technology is a Computer Algebra System (CAS). This study investigated the beliefs about CAS held by twelve Year 11 students as they learnt to use CAS and whether these beliefs were stable over time. These students held a range of beliefs related to the usefulness of CAS, speed of CAS compared to P&P, whether CAS is proper mathematics, choice of CAS or P&P, ease of use, the correctness of answers and solving problems in Mathematical Methods (i.e. the mathematics subject studied). Beliefs are often described as being stable (e.g. McLeod, 1992), but some researchers stress stability needs to be determined empirically rather than being seen as a characteristic of beliefs (e.g. Liljedahl et al., 2012). For this sample of students, stability (rather than instability) is a feature of students' beliefs about CAS.

Blended Synchronous Learning (BSL) refers to when students located in physical classrooms learn together with peers who attend remotely, via networked digital technologies. The COVID-19 pandemic, along with ambitions to increase flexibility in learning delivery mode for students, has led to the increased implementation of BSL in tertiary education. The current evidence-base around BSL provides important principles for its use, but relatively little research has examined the experiences of teaching staff in depth. This article uses a self-study methodology to explore educators' experiences of BSL implementation in a post-graduate Initial Teacher Education course in Australia. Six teaching staff, all co-researchers for the study, contributed reflective data, and engaged in analysis and interpretation of the data via structured critical friendships. Insights related to four key themes were derived from the analysis: institutional and pedagogical factors; educator wellbeing, self-efficacy and professional identity; staffing support; and collegial professional learning. The implementation of BSL, while aligned with existing recommendations, produced significant challenges for educators in relation to institutional support and training, pedagogical practices, operation of BSL technologies, professional identity and self-efficacy. Cognitive overload was a prominent feature of the BSL teaching experience. On the whole, while drawing on existing skills and teaching experience, educators held significant concerns with the overall quality of student learning in BSL--especially for remote students. Training, practice, technical and co-teaching support, as well as collegial relationships, were important mediators of educator experience. The findings suggest that the implementation of BSL requires substantial investment in staffing, training, skill development, and opportunities for authentic, meaningful practice and prototyping. The findings also affirm the value of timely, organisationally supported and collaborative professional learning as part of BSL implementation.

This article demonstrates how educators can create opportunities for students to learn about leadership in a variety of circumstances. Through the integrated model for contextualizing leadership learning, educators can center culturally relevant leadership while considering the environment where leadership learning is provided as well as the context in which the identity, capacity, and effectiveness of leadership educators are developed. The implications of this integrated approach emerged from 26 narratives and are explored through three themes centered on co-curricular program development and implementation, as well as personal and professional development. These themes include examining organizations' histories and structures, the developmental readiness of educators and students, and the significance of context.

Laser-driven ion acceleration provides ultrashort, high-charge, low-emittance beams, which are desirable for a wide range of high-impact applications. Yet after decades of research, a significant increase in maximum ion energy is still needed. This paper introduces a quality-preserving staging concept for ultraintense ion bunches that is seamlessly applicable from the nonrelativistic plasma source to the relativistic regime. Full three-dimensional particle-in-cell simulations prove robustness and capture of a high-charge proton bunch, suitable for readily available and near-term laser facilities. Published by the American Physical Society 2024

A primary goal of psychiatry is to better understand the pathways that link genetic risk to psychiatric symptoms. Here, we tested association of diagnosis and endophenotypes with overall and neurotransmitter pathway-specific polygenic risk in patients with early-stage psychosis. Subjects included 205 demographically diverse cases with a psychotic disorder who underwent comprehensive psychiatric and neurological phenotyping and 115 matched controls. Following genotyping, we calculated polygenic scores (PGSs) for schizophrenia (SZ) and bipolar disorder (BP) using Psychiatric Genomics Consortium GWAS summary statistics. To test if overall genetic risk can be partitioned into affected neurotransmitter pathways, we calculated pathway PGSs (pPGSs) for SZ risk affecting each of four major neurotransmitter systems: glutamate, GABA, dopamine, and serotonin. Psychosis subjects had elevated SZ PGS versus controls; cases with SZ or BP diagnoses had stronger SZ or BP risk, respectively. There was no significant association within psychosis cases between individual symptom measures and overall PGS. However, neurotransmitter-specific pPGSs were moderately associated with specific endophenotypes; notably, glutamate was associated with SZ diagnosis and with deficits in cognitive control during task-based fMRI, while dopamine was associated with global functioning. Finally, unbiased endophenotype-driven clustering identified three diagnostically mixed case groups that separated on primary deficits of positive symptoms, negative symptoms, global functioning, and cognitive control. All clusters showed strong genome-wide risk. Cluster 2, characterized by deficits in cognitive control and negative symptoms, additionally showed specific risk concentrated in glutamatergic and GABAergic pathways. Due to the intensive characterization of our subjects, the present study was limited to a relatively small cohort. As such, results should be followed up with additional research at the population and mechanism level. Our study suggests pathway-based PGS analysis may be a powerful path forward to study genetic mechanisms driving psychiatric endophenotypes.

The Cerebellar Cognitive Affective/Schmahmann Syndrome (CCAS) manifests as impaired executive control, linguistic processing, visual spatial function, and affect regulation. The CCAS has been described in the spinocerebellar ataxias (SCAs), but its prevalence is unknown. We analyzed results of the CCAS/Schmahmann Scale (CCAS-S), developed to detect and quantify CCAS, in two natural history studies of 309 individuals Symptomatic for SCA1, SCA2, SCA3, SCA6, SCA7, or SCA8, 26 individuals Pre-symptomatic for SCA1 or SCA3, and 37 Controls. We compared total raw scores, domain scores, and total fail scores between Symptomatic, Pre-symptomatic, and Control cohorts, and between SCA types. We calculated scale sensitivity and selectivity based on CCAS category designation among Symptomatic individuals and Controls, and correlated CCAS-S performance against age and education, and in Symptomatic patients, against genetic repeat length, onset age, disease duration, motor ataxia, depression, and fatigue. Definite CCAS was identified in 46% of the Symptomatic group. False positive rate among Controls was 5.4%. Symptomatic individuals had poorer global CCAS-S performance than Controls, accounting for age and education. The domains of semantic fluency, phonemic fluency, and category switching that tap executive function and linguistic processing consistently separated Symptomatic individuals from Controls. CCAS-S scores correlated most closely with motor ataxia. Controls were similar to Pre-symptomatic individuals whose nearness to symptom onset was unknown. The use of the CCAS-S identifies a high CCAS prevalence in a large cohort of SCA patients, underscoring the utility of the scale and the notion that the CCAS is the third cornerstone of clinical ataxiology.

Neuroendocrine analyses of posttraumatic stress disorder (PTSD) have generally focused on hypothalamic-pituitary-adrenal (HPA) axis alterations. In the present analyses, we examine two additional neuroendocrine factors that have been previously implicated in biological stress responses: oxytocin (OT) and arginine vasopressin (AVP). Here we examined basal neuropeptide status in military veterans clinically diagnosed with PTSD (n = 29) and in two non-traumatized comparison groups with previous stress exposure (n = 11 SWAT trainees and n = 21 ultramarathon runners). PTSD patients showed low levels of plasma OT and high levels of AVP. The ratio of AVP/OT robustly related to PTSD status, and emerged as a statistically plausible mediator of relationships between the number of personal traumatic experiences and subsequent PTSD symptom burden. Over the course of behavioral therapy for PTSD, measures of OT showed a significant but modest normalization. Plasma cortisol levels were not statistically different among the three groups. This study suggests that AVP/OT ratios may represent a neuroendocrine predictor of severe PTSD, as well as a potential treatment response biomarker.

The prevalence of "long COVID" is just one of the conundrums highlighting how little we know about the lung's response to viral infection, particularly to syndromecoronavirus-2 (SARS-CoV-2), for which the lung is the point of entry. We used an in vitro human lung system to enable a prospective, unbiased, sequential single-cell level analysis of pulmonary cell responses to infection by multiple SARS-CoV-2 strains. Starting with human induced pluripotent stem cells and emulating lung organogenesis, we generated and infected three-dimensional, multi-cell-type-containing lung organoids (LOs) and gained several unexpected insights. First, SARS-CoV-2 tropism is much broader than previously believed: Many lung cell types are infectable, if not through a canonical receptor-mediated route (e.g., via Angiotensin-converting encyme 2(ACE2)) then via a noncanonical "backdoor" route (via macropinocytosis, a form of endocytosis). Food and Drug Administration (FDA)-approved endocytosis blockers can abrogate such entry, suggesting adjunctive therapies. Regardless of the route of entry, the virus triggers a lung-autonomous, pulmonary epithelial cell-intrinsic, innate immune response involving interferons and cytokine/chemokine production in the absence of hematopoietic derivatives. The virus can spread rapidly throughout human LOs resulting in mitochondrial apoptosis mediated by the prosurvival protein Bcl-xL. This host cytopathic response to the virus may help explain persistent inflammatory signatures in a dysfunctional pulmonary environment of long COVID. The host response to the virus is, in significant part, dependent on pulmonary Surfactant Protein-B, which plays an unanticipated role in signal transduction, viral resistance, dampening of systemic inflammatory cytokine production, and minimizing apoptosis. Exogenous surfactant, in fact, can be broadly therapeutic.

Abstract: Large Language Models (LLMs) have been criticized for failing to connect linguistic meaning to the world—for failing to solve the “symbol grounding problem.” Multimodal Large Language Models (MLLMs) offer a potential solution to this challenge by combining linguistic representations and processing with other modalities. However, much is still unknown about exactly how and to what degree MLLMs integrate their distinct modalities—and whether the way they do so mirrors the mechanisms believed to underpin grounding in humans. In humans, it has been hypothesized that linguistic meaning is grounded through “embodied simulation,” the activation of sensorimotor and affective representations reflecting described experiences. Across four pre-registered studies, we adapt experimental techniques originally developed to investigate embodied simulation in human comprehenders to ask whether MLLMs are sensitive to sensorimotor features that are implied but not explicit in descriptions of an event. In Experiment 1, we find sensitivity to some features (color and shape) but not others (size, orientation, and volume). In Experiment 2, we identify likely bottlenecks to explain an MLLM’s lack of sensitivity. In Experiment 3, we find that despite sensitivity to implicit sensorimotor features, MLLMs cannot fully account for human behavior on the same task. Finally, in Experiment 4, we compare the psychometric predictive power of different MLLM architectures and find that ViLT, a single-stream architecture, is more predictive of human responses to one sensorimotor feature (shape) than CLIP, a dual-encoder architecture—despite being trained on orders of magnitude less data. These results reveal strengths and limitations in the ability of current MLLMs to integrate language with other modalities, and also shed light on the likely mechanisms underlying human language comprehension.

Complete representation of rainfall–runoff responses in complex, large watersheds using a single-objective parameterization approach in watershed models is often unachievable. In this study we present a calibration approach for the SWAT+ model that independently fits model parameters for different flow segments of the hydrograph. The approach is demonstrated for the Feather River, California, USA, using daily streamflow from the Lake Oroville Reservoir outlet gage. Results show that when model parameters were independently fitted for different flow segments the KGE, NSE, PBIAS, and RSR values improved to 0.96, 0.99, −3.3, and 0.10, respectively, compared to 0.72, 0.66, −9.30, and 0.53, respectively, achieved under a multiobjective and full hydrograph (average hydrograph) calibration. The results highlight that when considering the average hydrograph and flow duration curves, a more balanced representation of both poorly and well-performing segments is achieved, emphasizing the importance of segment-specific parameterization and multi-objective evaluation for accurately representing different flow conditions.

Theories of psychotic illness suggest that abnormal intrinsic functional connectivity may explain its characteristic positive and disorganization symptoms as well as lead to impaired general functioning. Here we used resting state functional magnetic resonance imaging (fMRI) to evaluate associations between these symptoms and the degree to which global connectivity is abnormal in early psychosis (EP). Eighty-six healthy controls (HCs) and 108 individuals with EP with resting state fMRI data were included in primary analyses. The EP group included 83 participants with schizophrenia-spectrum disorders and 25 with bipolar disorder type I with psychotic features. A global intrinsic connectivity "similarity index" for each EP individual was determined by calculating its correlation with the average HC connectivity matrix extracted using Schaefer atlases of multiple parcellations (100, 200, 300, and 400 region parcellations). As hypothesized, connectivity similarity with the average HC matrix was negatively associated with Brief Psychiatric Rating Scale total score, Scale for the Assessment of Positive Symptoms total score, and disorganization symptoms. Similarity was also positively associated with Global Assessment of Functioning score. Results were not driven by sex or diagnosis effects and were consistent across parcellation schemes. These results support the hypothesis that changes in whole-brain connectivity patterns are associated with psychosis symptoms and support the use of functional connectivity as a biomarker for these symptoms in EP.

The dry mass and the orientation of biomolecules can be imaged without a label by measuring their permittivity tensor (PT), which describes how biomolecules affect the phase and polarization of light. Three-dimensional (3D) imaging of PT has been challenging. We present a label-free computational microscopy technique, PT imaging (PTI), for the 3D measurement of PT. PTI encodes the invisible PT into images using oblique illumination, polarization-sensitive detection and volumetric sampling. PT is decoded from the data with a vectorial imaging model and a multi-channel inverse algorithm, assuming uniaxial symmetry in each voxel. We demonstrate high-resolution imaging of PT of isotropic beads, anisotropic glass targets, mouse brain tissue, infected cells and histology slides. PTI outperforms previous label-free imaging techniques such as vector tomography, ptychography and light-field imaging in resolving the 3D orientation and symmetry of organelles, cells and tissue. We provide open-source software and modular hardware to enable the adoption of the method.

BACKGROUND: Given the complexity of arthroscopic rotator cuff repair (ARCR) and increasing prevalence, there is a need for comprehensive, large-scale studies that investigate potential correlations between surgeon-specific factors and postoperative outcomes after ARCR. This study examines how surgeon-specific factors including case volume, career length, fellowship training, practice setting, and regional practice impact two-year reoperation rates, conversion to total shoulder arthroplasty (anatomic or reverse), and 90-day post-ARCR hospitalization. METHODS: The PearlDiver Mariner database was used to collect surgeon-specific variables and query patients who underwent ARCR from 2015 to 2018. Patient outcomes were tracked for two years, including reoperations, hospitalizations, and International Classification of Diseases, Tenth Revision codes for revision rotator cuff repair (RCR) laterality. Hospitalizations were defined as any emergency department (ED) visit or hospital readmission within 90 days after primary ARCR. Surgeon-specific factors including surgeon case volume, career length, fellowship training, practice setting, and regional practice were analyzed in relation to postoperative outcomes using both univariate and multivariate logistic regression. RESULTS: 94,150 patients underwent ARCR by 1489 surgeons. On multivariate analysis, high-volume surgeons demonstrated a higher risk for two-year total reoperation (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.01-1.12, P = .03) and revision RCR (OR = 1.06, 95% CI: 1.01-1.12, P = .02) compared to low-volume surgeons. Early-career surgeons showed higher rates of 90-day ED visits (mid-career surgeons: OR = 0.78, 95% CI: 0.73-0.83, P

Chest wall pain syndromes can emerge following local therapies for lung cancer and can adversely affect patients quality-of-life. This can occur after lung surgery, radiation therapy, or percutaneous image-guided thermal ablation. This review describes the multifactorial pathophysiology of chest wall pain syndromes that develop following surgical and non-surgical local therapies for lung cancer and summarizes evidence-based management strategies for inflammatory, neuropathic, myofascial, and osseous pain. It discusses a step-wise approach to treating chest wall pain that begins with non-opioid oral analgesics and includes additional pharmacologic treatments as clinically indicated, such as anticonvulsants, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, and various topical treatments. For myofascial pain, physical medicine techniques, such as acupuncture, trigger point injections, deep tissue massage, and intercostal myofascial release can also offer pain relief. For severe or refractory cases, opioid analgesics, intercostal nerve blocks, or intercostal nerve ablations may be indicated. Fortunately, palliation of treatment-related chest wall pain syndromes can be managed by most clinical providers, regardless of the type of local therapy utilized for a patients lung cancer treatment. In cases where a patients pain fails to respond to initial medical management, clinicians can consider referring to a pain specialist who can tailor a more specific pharmacologic approach or perform a procedural intervention to relieve pain.

Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5.

STUDY OBJECTIVE: African Americans (AAs) show early signs of vascular dysfunction paired with elevated blood pressure (BP) and total peripheral resistance (TPR), which is thought to underlie their increased rates of cardiovascular health complications relative to European Americans (EAs). AAs paradoxically have higher cardiac vagal tone, indexed by heart rate variability (HRV), which is cardio-protective. This paradox has been termed the Cardiovascular Conundrum. The physiological mechanism underlying this phenomenon is not well understood. We examined race differences in baroreflex function, which might be an important mechanism underlying the Cardiovascular Conundrum. DESIGN: Participants completed a 5-minute baseline period where resting cardiac metrics were assessed. SETTING: Laboratory. PARTICIPANTS: 130 college-aged individuals (54 women, 57 AAs). MAIN OUTCOME MEASURES: Baroreflex function was indexed as baroreflex sensitivity (BRS; the magnitude of changes in cardiovascular activity in accordance with BP changes) and effectiveness (BEI; the ratio of BP changes that elicit changes in cardiovascular activity) in the cardiac, vascular, and myocardial limbs. RESULTS AND CONCLUSIONS: Results showed AAs to have higher HRV and cardiac BRS in comparison to EAs, suggesting the baroreflex is more sensitive to correcting the heart period for changes in BP among AAs compared to EAs. However, AAs showed lower vascular BEI relative to EAs, suggesting less effective control of TPR. In sum, lower BEI in the vascular branch might be an important mechanism underlying the Cardiovascular Conundrum (i.e., higher HRV and BP) and by extension, health disparities in cardiovascular diseases between AAs and EAs.

Abstract: We address a growing debate about the extent to which large language models (LLMs) produce behavior consistent with Theory of Mind (ToM) in humans. We present EPITOME: a battery of six experiments that tap diverse ToM capacities, including belief attribution, emotional inference, and pragmatic reasoning. We elicit a performance baseline from human participants for each task. We use the dataset to ask whether distributional linguistic information learned by LLMs is sufficient to explain ToM in humans. We compare performance of five LLMs to a baseline of responses from human comprehenders. Results are mixed. LLMs display considerable sensitivity to mental states and match human performance in several tasks. Yet, they commit systematic errors in others, especially those requiring pragmatic reasoning on the basis of mental state information. Such uneven performance indicates that human-level ToM may require resources beyond distributional information.

OBJECTIVE: Nursing home residents may be particularly vulnerable to coronavirus disease 2019 (COVID-19). Therefore, a question is when and how often nursing homes should test staff for COVID-19 and how this may change as severe acute respiratory coronavirus virus 2 (SARS-CoV-2) evolves. DESIGN: We developed an agent-based model representing a typical nursing home, COVID-19 spread, and its health and economic outcomes to determine the clinical and economic value of various screening and isolation strategies and how it may change under various circumstances. RESULTS: Under winter 2023-2024 SARS-CoV-2 omicron variant conditions, symptom-based antigen testing averted 4.5 COVID-19 cases compared to no testing, saving $191 in direct medical costs. Testing implementation costs far outweighed these savings, resulting in net costs of $990 from the Centers for Medicare & Medicaid Services perspective, $1,545 from the third-party payer perspective, and $57,155 from the societal perspective. Testing did not return sufficient positive health effects to make it cost-effective [$50,000 per quality-adjusted life-year (QALY) threshold], but it exceeded this threshold in ≥59% of simulation trials. Testing remained cost-ineffective when routinely testing staff and varying face mask compliance, vaccine efficacy, and booster coverage. However, all antigen testing strategies became cost-effective (≤$31,906 per QALY) or cost saving (saving ≤$18,372) when the severe outcome risk was ≥3 times higher than that of current omicron variants. CONCLUSIONS: SARS-CoV-2 testing costs outweighed benefits under winter 2023-2024 conditions; however, testing became cost-effective with increasingly severe clinical outcomes. Cost-effectiveness can change as the epidemic evolves because it depends on clinical severity and other intervention use. Thus, nursing home administrators and policy makers should monitor and evaluate viral virulence and other interventions over time.

Microbial genome sequences are rapidly accumulating, enabling large-scale studies of sequence variation. Existing studies primarily focus on coding regions to study amino acid substitution patterns in proteins. However, non-coding regulatory regions also play a distinct role in determining physiologic responses. To investigate intergenic sequence variation on a large-scale, we identified non-coding regulatory region alleles across 2350 Escherichia coli strains. This alleleome consists of 117 781 unique alleles for 1169 reference regulatory regions (transcribing 1975 genes) at single base-pair resolution. We find that 64% of nucleotide positions are invariant, and variant positions vary in a median of just 0.6% of strains. Additionally, non-coding alleles are sufficient to recover E. coli phylogroups. We find that core promoter elements and transcription factor binding sites are significantly conserved, especially those located upstream of essential or highly-expressed genes. However, variability in conservation of transcription factor binding sites is significant both within and across regulons. Finally, we contrast mutations acquired during adaptive laboratory evolution with wild-type variation, finding that the former preferentially alter positions that the latter conserves. Overall, this analysis elucidates the wealth of information found in E. coli non-coding sequence variation and expands pangenomic studies to non-coding regulatory regions at single-nucleotide resolution.

Food insecurity is highly prevalent and linked to poorer diet and worse metabolic outcomes. Food insecurity can be stressful, and could elicit chronic psychological and physiological stress. In this study, we tested whether stress could be used to identify those at highest risk for worse diet and metabolic measures from food insecurity. Specifically, we hypothesized that cortisol (a physiological marker of stress) and perceived psychological stress would amplify the link between food insecurity and hyperpalatable food intake as well as metabolic measures. In a sample of 624 Black and White women aged 36-43 who participated in the NHLBI Growth and Health Study's midlife assessment, we assessed associations between food insecurity with hyperpalatable food intake (high fat + high sodium foods; high fat + high sugar foods; and high carbohydrate + high sodium foods), and metabolic measures (fasting glucose, insulin resistance, and waist circumference). We found that food insecurity was associated with higher levels of perceived stress (R2 = 0.09), and greater intake of high fat + high sugar (hyperpalatable) foods (R2 = 0.03). In those with higher cumulative cortisol (as indexed by hair cortisol), food insecurity was associated with higher levels of fasting glucose. Neither cortisol nor perceived stress moderated any other relationships, and neither variable functioned as a mediator in sensitivity analyses. Given these largely null findings, further research is needed to understand the role stress plays in the chronic health burdens of food insecurity.

* Context.-Artificial intelligence algorithms hold the potential to fundamentally change many aspects of society. Application of these tools, including the publicly available ChatGPT, has demonstrated impressive domain-specific knowledge in many areas, including medicine. Objectives.-To understand the level of pathology domain-specific knowledge for ChatGPT using different underlying large language models, GPT-3.5 and the updated GPT-4. Design.-An international group of pathologists (n = 15) was recruited to generate pathology-specific questions at a similar level to those that could be seen on licensing (board) examinations. The questions (n = 15) were answered by GPT-3.5, GPT-4, and a staff pathologist who recently passed their Canadian pathology licensing exams. Participants were instructed to score answers on a 5-point scale and to predict which answer was written by ChatGPT. Results.-GPT-3.5 performed at a similar level to the staff pathologist, while GPT-4 outperformed both. The overall score for both GPT-3.5 and GPT-4 was within the range of meeting expectations for a trainee writing licensing examinations. In all but one question, the reviewers were able to correctly identify the answers generated by GPT-3.5. Conclusions.-By demonstrating the ability of ChatGPT to answer pathology-specific questions at a level similar to (GPT-3.5) or exceeding (GPT-4) a trained pathologist, this study highlights the potential of large language models to be transformative in this space. In the future, more advanced iterations of these algorithms with increased domain-specific knowledge may have the potential to assist pathologists and enhance pathology resident training. (Arch Pathol Lab Med. 2024;148:1152-1158; doi: 10.5858/arpa.2023-0296-OA), Rapid technological advancements in molecular pathology and a continuously growing body of knowledge have resulted in an unprecedented increase in diagnostic complexity for pathologists. (1) This presents a challenge for [...]