Luck of the Draw: Enhancing Safety in Equine University Sport

Equestrian sports have the highest rates of injury across all sports with traumatic brain injury rates twice as high as those in football. The goal of this project is to make our university Intercollegiate Horse Show Association (IHSA) athletes safer by creating an easy-to-use tool that athletes can apply to evaluate new horses they ride at competitions. The tool guides team members through evaluation techniques by providing important safety dimensions and scoring guidelines. An undergraduate majoring in biology with an interest in Veterinarian specialization developed the diagnostic tool. The tool allows evaluation of movement/quality of gaits, jumping ability, equine personality, equipment fit, conformation, and rider’s affect. Three different methods assess usefulness of this tool and suggest refinements. The first method is qualitative face-to-face interviews with equine professionals who will provide expert information about the perceived usefulness of the diagnostic tool. The second method is qualitative face-to-face interviews with English BGSU Equestrian Team (BGET) members to study the personal techniques used when evaluating unfamiliar horses at shows. Finally, BGET English members use the tool to evaluate horses at their training facility, assessing reliability and validity, followed by an online quantitative survey about the tool’s performance and usefulness. This project contributes to equestrian safety by creating a quick, simple tool to evaluate factors that affect competition on unfamiliar horses

A novel chlorhexidine-hexametaphosphate coating for titanium with antibiofilm efficacy and stem cell cytocompatibility

Abstract Dental implants are an increasingly popular way to replace missing teeth. Whilst implant survival rates are high, a small number fail soon after placement, with various factors, including bacterial contamination, capable of disrupting osseointegration. This work describes the development of chlorhexidine-hexametaphosphate coatings for titanium that hydrolyse to release the antiseptic agent chlorhexidine. The aim was to develop a coating for titanium that released sufficient chlorhexidine to prevent biofilm formation, whilst simultaneously maintaining cytocompatibility with cells involved in osseointegration. The coatings were characterised with respect to physical properties, after which antibiofilm efficacy was investigated using a multispecies biofilm model, and cytocompatibility determined using human mesenchymal stem cells. The coatings exhibited similar physicochemical properties to some implant surfaces in clinical use, and significantly reduced formation of multispecies biofilm biomass up to 72 h. One coating had superior cytocompatibility, with mesenchymal stem cells able to perform normal functions and commence osteoblastic differentiation, although at a slower rate than those grown on uncoated titanium. With further refinement, these coatings may have application in the prevention of bacterial contamination of dental implants at the time of surgery. This could aid a reduction in rates of early implant failure

Patient and provider experiences with virtual care during the COVID-19 pandemic: A mixed methods study

The COVID-19 pandemic prompted the rapid uptake of Virtual Care (VC). Positive patient outcomes with VC are previously reported but little is known about the experiences of patients and providers using VC during the pandemic. We aimed to describe patient and primary care provider experiences, satisfaction, perceptions, and attitudes to VC during the COVID-19 pandemic that might explain adoption of VC across the continuum of care and inform sustained uptake. We conducted a sequential explanatory mixed methods study using online surveys and virtual interviews with a convenience sample of primary care providers and patients in a Canadian province (July – December 2020). Eligible participants included patients and primary care providers using VC during the COVID-19 pandemic. Survey responses and interviews were analyzed using descriptive statistics and thematic analysis, respectively. Overall satisfaction was compared using the Mann-Whitney U test. Eighty-five patients and 94 primary care providers responded to the surveys. Patients reported higher overall satisfaction with VC than primary care providers (median [interquartile range]: 4.4 [4.0-4.7] and 3.7 [3.4-3.9] p \u3c 0.001). Ten patients and 11 primary care providers were interviewed. Both groups strongly appreciated VC’s increased access and convenience, identified the lack of compensation as a pre-pandemic barrier to providing VC, and reported willingness to continue VC post-COVID-19 pandemic. The COVID-19 pandemic provided an opportunity for patients and primary care providers to rapidly adopt VC with high satisfaction. Patients and primary care providers viewed VC positively due to its convenience and accessibility; both intend to continue using VC post-pandemic. Experience Framework This article is associated with the Staff & Provider Engagement lens of The Beryl Institute Experience Framework (https://www.theberylinstitute.org/ExperienceFramework). Access other PXJ articles related to this lens. Access other resources related to this lens

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

focus groups in migration research a forum for public thinking

This chapter outlines how to use focus groups (FGs) in migration studies, considering this method a forum for "public thinking" and discussing controversial issues. Moreover, the use of FGs allows us to understand the process of creating consensus and dissent via interaction. The chapter is structured in five sections: the first one introduces what FGs are and why they are useful for migration research; the second focuses on how to build the groups and how to do comparative migration research with FGs; the third illustrates how to prepare and to facilitate group discussion, and how to ask questions and engage participants in collaborative migration research; the fourth introduces how to interpret discussions and how to analyse the everyday naturalization of nation, ethnicity and race; the final section discusses how to communicate FG results. Each section is devoted to a specific methodological issue and it includes at least one "box" with an example from European migration research

Foxp3(+) regulatory T cells, Th17 effector cells, and cytokine environment in inflammatory bowel disease

Background: Inflammatory bowel disease (IBD) is thought to result from an aberrant immune response. Inflammation in IBD may be caused by the loss of homeostasis between CD4+ CD25high Foxp3+ regulatory cells (T reg) and proinflammatory Th17 cells. The aim of this study was to investigate T reg and Th17 cells in the peripheral blood and intestinal mucosa of IBD patients and to assess the mucosal cytokine environment. Methods: T reg and Th17 cells were measured in peripheral blood of 63 IBD patients and 28 controls by flow cytometry. Forkhead box p3 (Foxp3), interleukin (IL)-17a, IL-1β, IL-6, IL-21, IL-23, and transforming growth factor (TGF)-β mRNA were analyzed using real-time reverse transcription polymerase chain reaction in intestinal biopsies of 24 IBD and 18 control subjects. Results: A decrease in T reg and increase in Th17 cells was observed in the peripheral blood of IBD patients. When measured in the same patient and expressed as a ratio, a significant decrease in T reg/Th17 ratio was observed in IBD. Elevated expression of Foxp3, IL-17a, IL-1β, and IL-6 was observed in the mucosa of IBD patients, while TGF-β was only elevated in ulcerative colitis. Conclusion: IBD is associated with a reduced ratio of T reg to Th17 cells in peripheral blood and is characterized by a proinflammatory cytokine microenvironment, which supports the continued generation of Th17 cells.Nicola Eastaff-Leung, Nicholas Mabarrack, Angela Barbour, Adrian Cummins and Simon Barr