Considering a Model of Support for At Risk Children in Rural Appalachian Communities

Many children in rural Appalachia are at risk for school dropout, substance abuse, risky sexual behavior and mental health disorders due to sparse resources and limited support systems within the family and the community. The resources that are available to assist children in rural Appalachia may be underutilized due to limited understanding of resource availability and other limitations (e.g., geographical, limited finances). The purpose of this presentation is to discuss methods of building healthy communities for children at risk through accessing a “natural helper framework” inherent in many Appalachian communities. The presentation will discuss accessing religious communities, extended family care, and other resources that may be available to Appalachian families. Additionally, it will discuss the unique needs for children at risk for socioemotional and academic failure and a model for analyzing and accessing available resources that can be present when mental health resources are lacking

Emergency admission predictive risk stratification models: assessment of implementation consequences (PRISMATIC 2): protocol for a mixed methods study.

Emergency admissions are costly, increasingly numerous, and associated with adverse patient outcomes. Policy responses have included the widespread introduction of emergency admission risk stratification (EARS) tools in primary care. These tools generate scores that predict patients' risk of emergency hospital admission and can be used to support targeted approaches to improve care and reduce admissions. However, the impact of EARS is poorly understood and there may be unintended consequences. To assess effects, mechanisms, costs, and patient and healthcare professionals' views related to the introduction of EARS tools in England. Quasi-experimental mixed methods design using anonymised routine data and qualitative methods. We will apply multiple interrupted time series analysis to data, aggregated at former Clinical Commissioning Group level, to look at changes in emergency admission and other healthcare use following EARS introduction across England. We will investigate GP decision-making at practice level using linked general practice and secondary care data to compare case-mix, demographics, indicators of condition severity and frailty associated with emergency admissions before and after EARS introduction. We will undertake interviews ( ~48) with GPs and healthcare staff to understand how patient care may have changed. We will conduct focus groups ( =2) and interviews ( ~16) with patients to explore how they perceive that communication of individual risk scores might affect their experiences and health seeking behaviours. Findings will provide policymakers, healthcare professionals, and patients, with a better understanding of the effects, costs and stakeholder perspectives related to the introduction of EARS tools. [Abstract copyright: Copyright © 2024, The Authors.

Modeling Progressive Fibrosis with Pluripotent Stem Cells Identifies an Anti-fibrotic Small Molecule.

Progressive organ fibrosis accounts for one-third of all deaths worldwide, yet preclinical models that mimic the complex, progressive nature of the disease are lacking, and hence, there are no curative therapies. Progressive fibrosis across organs shares common cellular and molecular pathways involving chronic injury, inflammation, and aberrant repair resulting in deposition of extracellular matrix, organ remodeling, and ultimately organ failure. We describe the generation and characterization of an in vitro progressive fibrosis model that uses cell types derived from induced pluripotent stem cells. Our model produces endogenous activated transforming growth factor β (TGF-β) and contains activated fibroblastic aggregates that progressively increase in size and stiffness with activation of known fibrotic molecular and cellular changes. We used this model as a phenotypic drug discovery platform for modulators of fibrosis. We validated this platform by identifying a compound that promotes resolution of fibrosis in in vivo and ex vivo models of ocular and lung fibrosis

The successes and challenges of harmonising juvenile idiopathic arthritis (JIA) datasets to create a large-scale JIA data resource

Background CLUSTER is a UK consortium focussed on precision medicine research in JIA/JIA-Uveitis. As part of this programme, a large-scale JIA data resource was created by harmonizing and pooling existing real-world studies. Here we present challenges and progress towards creation of this unique large JIA dataset. Methods Four real-world studies contributed data; two clinical datasets of JIA patients starting first-line methotrexate (MTX) or tumour necrosis factor inhibitors (TNFi) were created. Variables were selected based on a previously developed core dataset, and encrypted NHS numbers were used to identify children contributing similar data across multiple studies. Results Of 7013 records (from 5435 individuals), 2882 (1304 individuals) represented the same child across studies. The final datasets contain 2899 (MTX) and 2401 (TNFi) unique patients; 1018 are in both datasets. Missingness ranged from 10 to 60% and was not improved through harmonisation. Conclusions Combining data across studies has achieved dataset sizes rarely seen in JIA, invaluable to progressing research. Losing variable specificity and missingness, and their impact on future analyses requires further consideration

2015 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1002/thumbnail.jp

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Phylogenetic evidence for the invasion of a commercialized European Phasmarhabditis hermaphrodita lineage into North America and New Zealand

Biological control (biocontrol) as a component of pest management strategies reduces reliance on synthetic chemicals, and seemingly offers a natural approach that minimizes environmental impact. However, introducing a new organism to new environments as a classical biocontrol agent can have broad and unanticipated biodiversity effects and conservation consequences. Nematodes are currently used in a variety of commercial biocontrol applications, including the use of Phasmarhabditis hermaphrodita as an agent targeting pest slug and snail species. This species was originally discovered in Germany, and is generally thought to have European origins. P. hermaphrodita is sold under the trade name Nemaslug®, and is available only in European markets. However, this nematode species was discovered in New Zealand and the western United States, though its specific origins remained unclear. In this study, we analyzed 45 nematode strains representing eight different Phasmarhabditis species, collected from nine countries around the world. A segment of nematode mitochondrial DNA (mtDNA) was sequenced and subjected to phylogenetic analyses. Our mtDNA phylogenies were overall consistent with previous analyses based on nuclear ribosomal RNA (rRNA) loci. The recently discovered P. hermaphrodita strains in New Zealand and the United States had mtDNA haplotypes nearly identical to that of Nemaslug®, and these were placed together in an intraspecific monophyletic clade with high support in maximum likelihood and Bayesian analyses. We also examined bacteria that co-cultured with the nematode strains isolated in Oregon, USA, by analyzing 16S rRNA sequences. Eight different bacterial genera were found to associate with these nematodes, though Moraxella osloensis, the bacteria species used in the Nemaslug® formulation, was not detected. This study provided evidence that nematodes deriving from the Nemaslug® biocontrol product have invaded countries where its use is prohibited by regulatory agencies and not commercially available

Terrestrial behavior in titi monkeys (Callicebus, Cheracebus, and Plecturocebus) : potential correlates, patterns, and differences between genera

For arboreal primates, ground use may increase dispersal opportunities, tolerance to habitat change, access to ground-based resources, and resilience to human disturbances, and so has conservation implications. We collated published and unpublished data from 86 studies across 65 localities to assess titi monkey (Callicebinae) terrestriality. We examined whether the frequency of terrestrial activity correlated with study duration (a proxy for sampling effort), rainfall level (a proxy for food availability seasonality), and forest height (a proxy for vertical niche dimension). Terrestrial activity was recorded frequently for Callicebus and Plecturocebus spp., but rarely for Cheracebus spp. Terrestrial resting, anti-predator behavior, geophagy, and playing frequencies in Callicebus and Plecturocebus spp., but feeding and moving differed. Callicebus spp. often ate or searched for new leaves terrestrially. Plecturocebus spp. descended primarily to ingest terrestrial invertebrates and soil. Study duration correlated positively and rainfall level negatively with terrestrial activity. Though differences in sampling effort and methods limited comparisons and interpretation, overall, titi monkeys commonly engaged in a variety of terrestrial activities. Terrestrial behavior in Callicebus and Plecturocebus capacities may bolster resistance to habitat fragmentation. However, it is uncertain if the low frequency of terrestriality recorded for Cheracebus spp. is a genus-specific trait associated with a more basal phylogenetic position, or because studies of this genus occurred in pristine habitats. Observations of terrestrial behavior increased with increasing sampling effort and decreasing food availability. Overall, we found a high frequency of terrestrial behavior in titi monkeys, unlike that observed in other pitheciids

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions