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Background and aimsDetailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.Approach and resultsA targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM were 9 years and 9.5 kPa. After adjusting for covariates, there were positive correlations among LSM and endoglin ( p = 0.04) and IL-8 ( p

Student engagement promotes communication and knowledge acquisition, a concept that is challenged in the online environment as few opportunities exist to physically connect instructors and learners. Limited research suggests that social media is a tool that can positively impact student engagement in the online classroom, which is especially relevant in the case of the COVID-19 pandemic and learning formats transitioning online. Specifically, Twitter, a favoured format for sharing news, entertainment, and professional networking, may provide a platform and an opportunity for engagement between students and the instructor outside of the traditional, formal classroom setting. This research explores how postsecondary students enrolled in two introductory online self-directed asynchronous courses used social media tools for personal, professional, and academic purposes and how Twitter, as a course evaluation requirement, contributed to interaction and engagement. Relying on 104 pre- and 34 post-semester surveys, our analysis revealed that while Twitter was not used as widely as other social media platforms, a notable proportion of students shared positive perceptions about Twitter's use. Further analysis revealed some polarizing results with recommendations for successfully implementing Twitter in online learning.

The Bali myna Leucopsar rothschildi has long suffered heavy trapping, leading to its near extinction in the wild and categorization as Critically Endangered on the IUCN Red List. Decades of conservation breeding, release of birds and post-release management at Bali Barat National Park have, until recently, failed to secure a viable wild population. However, over the past decade, population increases, expansion into new areas of the National Park and beyond, and successful breeding in both artificial and natural nest sites have occurred. These recent successes are associated with a change in approach by the National Park authority from concentrating efforts on the last refugium of the species (an area protected from trapping but with potentially suboptimal habitat) and towards the human-dominated landscapes around the main road through the National Park. Bali mynas tended to favour areas with extensive shorter grass cover and open canopies and to shun denser woodland. Anthropogenic landscapes such as farmland and plantations presumably mimic the original savannah habitat of the species, but nestbox provision has probably been crucial in these areas in the absence of natural cavities. A potential further factor in the increases in myna numbers and range has been a scheme involving local people in commercial breeding of the species, thereby reducing its market price, and working with communities to reduce trapping pressure. We encourage continuing operation of this management strategy inside the National Park and its further extension into adjacent tourist areas, which appear to have myna-friendly socio-ecological conditions.

The challenges and tensions experienced by mid-career faculty (MCF) can lead to frustration, disengagement, or leaving the professoriate altogether, a trend noted by researchers prior to and especially after the pandemic. In this article, we explore the role that collegial support and career reflection and assessment strategies targeting mid-career faculty can play to preserve institutional vitality, support faculty agency, and promote student success. Additionally, we propose initiatives and supports that may assist these faculty members in staying in the academy and staying well as they pursue professional fulfillment and work towards their goals, including promotion to full professorship. We contend that post-secondary campuses should invest in keeping MCF engaged because of the crucial roles they serve on campus.

Abstract Background Family violence, which includes intimate partner abuse, child abuse, and elder abuse, is a serious public health concern. Primary healthcare (PHC) offers a vital opportunity to identify and address family violence, yet barriers prevent the effective implementation of family violence interventions in PHC settings. The purpose of this study is to improve family violence identification and response in Alberta’s PHC settings by exploring readiness factors. Methods An integrated knowledge translation approach, combining implementation science and participatory action research, was employed to develop a readiness assessment tool for addressing family violence within PHC settings in Alberta. The research involved three phases: phase 1 involved a rapid evidence assessment, phase 2 engaged a panel of healthcare and family violence experts to explore readiness components in the Alberta context, and phase 3 utilized a 3-round Delphi consensus-building process to refine readiness indicators. Results Phase 1 findings from a rapid evidence assessment highlighted five main models/tools for assessing readiness to implement family violence interventions in PHC settings. In phase 2, additional concepts were identified through exploration with healthcare and family violence expert panel members, resulting in a total of 16 concepts for assessing family violence readiness within the Alberta PHC context. The 3-round Delphi consensus-building process in Phase 3 involved nine panelists, who collectively agreed on the inclusion of all concepts and indicators, yielding a total of 60 items for the proposed readiness assessment tool for addressing family violence in PHC within Alberta. Conclusion The current study lays the groundwork for future family violence intervention programs, offering insights into key components that promote readiness for implementing comprehensive programs and supporting PHC organizations in effectively addressing family violence.

Abstract Cells must sense and respond to sudden maladaptive environmental changes—stresses—to survive and thrive. Across eukaryotes, stresses such as heat shock trigger conserved responses: growth arrest, a specific transcriptional response, and biomolecular condensation of protein and mRNA into structures known as stress granules under severe stress. The composition, formation mechanism, adaptive significance, and even evolutionary conservation of these condensed structures remain enigmatic. Here we provide a remarkable view into stress-triggered condensation, its evolutionary conservation and tuning, and its integration into other well-studied aspects of the stress response. Using three morphologically near-identical budding yeast species adapted to different thermal environments and diverged by up to 100 million years, we show that proteome-scale biomolecular condensation is tuned to species-specific thermal niches, closely tracking corresponding growth and transcriptional responses. In each species, poly(A)-binding protein—a core marker of stress granules—condenses in isolation at species-specific temperatures, with conserved molecular features and conformational changes modulating condensation. From the ecological to the molecular scale, our results reveal previously unappreciated levels of evolutionary selection in the eukaryotic stress response, while establishing a rich, tractable system for further inquiry.

READY is a self-report prospective longitudinal study of deaf and hard of hearing (DHH) young people aged 16 to 19 years on entry. Its overarching aim is to explore the risk and protective factors for successful transition to adulthood. This article introduces the cohort of 163 DHH young people, background characteristics and study design. Focusing on self-determination and subjective well-being only, those who completed the assessments in written English (n = 133) score significantly lower than general population comparators. Sociodemographic variables explain very little of the variance in well-being scores; higher levels of self-determination are a predictor of higher levels of well-being, outweighing the influence of any background characteristics. Although women and those who are LGBTQ+ have statistically significantly lower well-being scores, these aspects of their identity are not predictive risk factors. These results add to the case for self-determination interventions to support better well-being amongst DHH young people.

Liquid droplets of biomolecules play key roles in organizing cellular behavior, and are also technologically relevant, yet physical studies of dynamic processes of such droplets have generally been lacking. Here, we investigate and quantify the dynamics of formation of dilute internal inclusions, i.e., vacuoles, within a model system consisting of liquid droplets of DNA 'nanostar' particles. When acted upon by DNA-cleaving restriction enzymes, these DNA droplets exhibit cycles of appearance, growth, and bursting of internal vacuoles. Analysis of vacuole growth shows their radius increases linearly in time. Further, vacuoles pop upon reaching the droplet interface, leading to droplet motion driven by the osmotic pressure of restriction fragments captured in the vacuole. We develop a model that accounts for the linear nature of vacuole growth, and the pressures associated with motility, by describing the dynamics of diffusing restriction fragments. The results illustrate the complex non-equilibrium dynamics possible in biomolecular condensates.

We examined the extent to which automated written expression curriculum-based measurement (aWE-CBM) can be accurately used to computer score student writing samples for screening and progress monitoring. Students (n = 174) with learning difficulties in Grades 1 to 12 who received 1:1 academic tutoring through a community-based organization completed narrative writing samples in the fall and spring across two academic years. The samples were evaluated using four automated and hand-calculated WE-CBM scoring metrics. Results indicated automated and hand-calculated scores were highly correlated at all four timepoints for counts of total words written (rs = 1.00), words spelled correctly (rs = 0.99-1.00), correct word sequences (CWS; rs = 0.96-0.97), and correct minus incorrect word sequences (CIWS; rs = 0.86-0.92). For CWS and CIWS, however, automated scores systematically overestimated hand-calculated scores, with an unacceptable amount of error for CIWS for some types of decisions. These findings provide preliminary evidence that aWE-CBM can be used to efficiently score narrative writing samples, potentially improving the feasibility of implementing multi-tiered systems of support in which the written expression skills of large numbers of students are screened and monitored.

Introduction Globally, 55 million individuals have dementia, with an increasing annual incident of 10 million. Enabling the development of new multi-modal models can improve the current diagnostic pathways and potentially contribute to early diagnosis and treatment of dementia. Here, we report how multi-modal resources is achieved within the successful Trusted Research Environment (TRE). Objectives We aimed to identify the challenges of the storage, distribution and analysis of neuroimaging data and how we could implement a comprehensive infrastructure to deal with these. The problems we specifically aimed to address were how to: anonymise scans, store large amounts of data, standardise datasets to a common format, extract metadata, provision the data, and allow for analysis. Methods We document various stages and capacities required for multi-modal neuroimaging analysis for dementia and conclude that achieving research ready assets to enable neuroimaging analysis for dementia from existing resources requires an engineered process to facilitate multiple aspects of curation, provisioning and large-scale analysis. Results We developed an ingest pipeline for neuroimaging data to meet the requirements set out in the objectives. This involved standardising all datasets to the Brain Imaging Data Structure, defacing scans and anonymising data, using MinIO for data storage and extracting metadata from header information for data discovery and provisioning. Conclusion The neuroimaging ingest pipeline developed has allowed for the distribution of imaging datasets within DPUK which has facilitated multi-modal research on anonymised and standardised data and enabled linkage with phenotypic and genomic data.

The Dementias Platform UK (DPUK) Data Portal holds over 60 cohort datasets from over 3 million participants with a range of multi-modal data including neuroimaging and genomics. This has meant we have seen an increasing interest in the development of AI models with the potential for clinical implementation. However, this presents a unique challenge to disclosure control when it comes to assessing these AI models for release due to the risk of attacks such as membership inference, model inversion or even just vulnerabilities in the models like overfitting. This is why we hosted a series of workshops bringing together members of the public, expert researchers, and data owners across the UK to build a framework for allowing the safe development and release of AI models trained on sensitive healthcare data. From this, we have put together recommendations and guidelines for the use of privacy-preserving techniques in AI models to protect patient privacy, and to allow the safe deployment of these models outside of trusted research environments. We also identified the unique challenges to privacy and implementation of privacy-preserving techniques in AI models regarding the use of complex data such as neuroimaging and genomics. This framework has created a path forward for supporting safe AI model development which takes into consideration rapidly evolving ethical, legal and privacy considerations.

The Capuchin Catacombs in Palermo, Sicily, have been home to non-adult mummified remains since the seventeenth century CE. Despite the increasing numbers of scientific studies conducted at this site, very little research has focused specifically on the youngest members of late modern (1787–1880 CE) society. This research aims to redress the balance by examining 43 individuals to gain insight into the demographic profile of mummified non-adults, to characterize their health status and possible cause of death, and to better understand the funerary treatment offered to the youngest members of society. A portable X-ray unit was used to capture anteroposterior and lateral images of each mummy; this facilitated age estimation, the identification of pathological and/traumatic lesions, and evidence of conservation and the mummification process more generally. This study revealed that regardless of age and health status at the time of death, the mortuary rite performed was primarily influenced by the wealth and social standing of the deceased’s kin. No demographic trends were observed in the data and the lack of evidence of metabolic, neoplastic, and traumatic bone lesions suggest these non-adults died from short-term, acute illnesses. Even when individuals did display evidence of chronic health conditions that would have impacted their day-to-day lives (e.g., B035), they were not excluded from this mortuary tradition on the basis of their long-term health and care requirements in life. Artifacts were found with all individuals examined and were associated with the mummification process, conservation of mummies, and/or their display. This research has ultimately demonstrated that non-invasive imaging can be used to gain a more comprehensive understanding of the lives and deaths of non-adults inhabiting late modern Palermo.

Introduction We undertook phenotypic characterization of early-onset and late-onset type 2 diabetes (T2D) in adult black African and white European populations with recently diagnosed T2D to explore ethnic differences in the manifestation of early-onset T2D.Research design and methods Using the Uganda Diabetes Phenotype study cohort of 500 adult Ugandans and the UK StartRight study cohort of 714 white Europeans with recently diagnosed islet autoantibody-negative T2D, we compared the phenotypic characteristics of participants with early-onset T2D (diagnosed at

Introduction Oral sucrose is repeatedly administered to neonates in the neonatal intensive care unit (NICU) to treat pain from commonly performed procedures; however, there is limited evidence on its long-term cumulative effect on neurodevelopment. We examined the association between total sucrose volumes administered to preterm neonates for pain mitigation in the NICU and their neurodevelopment at 18 months of corrected age (CA).Methods A prospective longitudinal single-arm observational study that enrolled hospitalised preterm neonates

The Paleogene cypraeoidean fauna of the northeast Pacific region (NEP), extending from Vancouver Island, British Columbia, Canada southward to Baja California Sur, México, consists of 12 genera, 20 named species (three of which are new), six open-nomenclature species, one Cypraeidae, indeterminate to genus and species, one cf. species, and four nomina dubia. All taxa are figured here. Species reassigned at the genus level are Protocypraea? simiensis (Nelson, 1925) and Luponovula maniobraensis (Squires and Advocate, 1986). Improved documentation of known NEP species include Propustularia kemperae (Nelson, 1925), Grovesia castacensis (Stewart, 1926) [1927]), G. mathewsonii (Gabb, 1864), and Eratotrivia crescentensis (Weaver and Palmer, 1922). The three new species, Subepona leahae, Bernaya kaylinae, and Eocypraea judithsmithae are from the upper lower Eocene Llajas Formation of Simi Valley, Ventura County and Devil Canyon, Los Angeles County, California. Six open-nomenclature species need better preserved material; they are: Bernaya sp., two Protocypraea? sp., Gisortia sp., Eocypraea sp., and Cypraedia sp., as does an indeterminate cypraeid from the Lodo Formation of central California. Nomina dubia are “Bernaya” fresnoensis (Anderson, 1905), “Eocypraea” bayerquei (Gabb, 1864), “Sphaerocypraea” martini (Dickerson, 1914), and “Sulcocypraea” oakvillensis (Van Winkle, 1918). Eratotrivia mackini (Durham, 1944) is herein reassigned to the synonymy of Grovesia mathewsonii (Gabb, 1869). The NEP Paleocene cypraeoidean fauna consists of four genera, a cypraeid of unknown generic affinity, and two nomina dubia. The early Eocene “Capay Stage” cypraeoidean fauna is comprised of eight genera and two nomina dubia. That was during the peak of NEP cypraeoidean biodiversity, which coincided with the “Early Eocene Climate Optimum” (EECO), the warmest time of the Paleogene. At the end of “Capay” time, biodiversity abruptly decreased, and this trend continued to the end of “Domengine Stage” time, when a faunal turnover took place. The cypraeoidean faunas in the subsequent “Tejon Stage” and Galvinian Stage continued to be diminished because of the ongoing cooling of the ocean waters. Continued global cooling eventually caused the disappearance of the thermophilic Paleogene NEP cypraeoideans before the beginning of the Oligocene. Most of the NEP cypraeoidean fauna is very similar morphologically to species found in the Tethys region of Europe, especially France, Italy, and Ukraine. These similar species are indicative that the introduction of most of the NEP cyraeoidean genera into the NEP region was via a westward-directed, warm-water current originating in the ancient Tethys Sea region of western Europe. The point of origin of the Paleocene Propustularia is unknown, and the late Eocene Nuceolaria most likely arrived in the NEP region via a Pacific Ocean route.

Introduction: Childhood obesity is a serious concern in the United States, with over one third of the pediatric population classified as obese. Abdominal pain is one of the most common chief complaints among pediatric emergency department (ED) visits. We hypothesized that overweight and obese children being evaluated in the ED for abdominal pain would have higher resource utilization than their normal and underweight peers.Methods: This was a retrospective review of pediatric patients