Project description:IntroductionMillions of out-of-hospital cardiac arrests (OHCA) occur globally each year. Survival after OHCA can be improved with the use of automated external defibrillators (AED). The main strategy for facilitating bystander defibrillation has been fixed-location public access defibrillators (PADs). New strategies of mobile AEDs depart from the model of static PADs and have the potential to address known barriers to early defibrillation and improve outcomes.MethodsMobile AEDs was one of six focus topics for the Wolf Creek XVII Conference held on June 14-17, 2023, in Ann Arbor, Michigan, USA. Conference invitees included international thought leaders and scientists in the field of cardiac arrest resuscitation from academia and industry. Participants submitted via online survey knowledge gaps, barriers to translation and research priorities for each focus topic. Expert panels used the survey results and their own perspectives and insights to create and present a preliminary unranked list for each category that was debated, revised, and ranked by all attendees to identify the top 5 for each category.ResultsTop knowledge gaps center around understanding the impact of mobile AEDs on OHCA outcomes in various settings and the impact of novel AED technologies. Top barriers to translation include questionable public comfort/acceptance, financial/regulatory constraints, and a lack of centralized accountability. Top research priorities focus on understanding the impact of the mobile AED strategies and technologies on time to defibrillation and OHCA outcomes.ConclusionThis work informs research agendas, funding priorities and policy decisions around using mobile AEDs to optimize prehospital response to OHCA.
Project description:Failure to restore spontaneous circulation remains a major cause of death for cardiac arrest (CA) patients. Mechanical circulatory support, specifically extracorporeal cardiopulmonary resuscitation (ECPR), has emerged as a feasible and efficacious rescue strategy for selected refractory CA patients. Mechanical Circulatory Support was one of six focus topics for the Wolf Creek XVII Conference held on June 14-17, 2023 in Ann Arbor, Michigan, USA. Conference invitees included international thought leaders and scientists in the field of CA resuscitation from academia and industry. Participants submitted via online survey knowledge gaps, barriers to translation and research priorities for each focus topic. Expert panels used the survey results and their own perspectives and insights to create and present a preliminary unranked list for each category that was debated, revised and ranked by all attendees to identify the top 5 for each category. Top 5 knowledge gaps included optimal patient selection, pre-ECPR treatments, logistical and programmatic characteristics of ECPR programs, generalizability and effectiveness of ECPR, and prevention of reperfusion injury. Top 5 barriers to translation included cost/resource limitations, technical challenges, collaboration across multiple disciplines, limited patient population, and early identification of eligible patients. Top 5 research priorities focused on comparing the outcomes of prehospital/rapid transport strategies vs in-hospital ECPR initiation, implementation of high-performing ECPR system vs standard care, rapid patient identification tools vs standard clinical judgment, post-cardiac arrest bundled care vs no bundled care, and standardized ECPR clinical protocol vs routine care. This overview can serve as an innovative guide to transform the care and outcome of patients with refractory CA.
Project description:IntroductionAutomated cardiac arrest diagnosis offers the possibility to significantly shorten the interval between onset of out-of-hospital cardiac arrest (OHCA) and notification of EMS, providing the opportunity for earlier resuscitation and possibly increased survival.MethodsAutomated cardiac arrest diagnosis was one of six focus topics for the Wolf Creek XVII Conference held on June 14-17 2023 in Ann Arbor, Michigan, USA. Conference invitees included international thought leaders and scientists in the field of cardiac arrest resuscitation from academia and industry. Participants submitted via online survey knowledge gaps, barriers to translation and research priorities for each focus topic. Expert panels used the survey results and their own perspectives and insights to create and present a preliminary unranked list for each category that was debated, revised and ranked by all attendees to identify the top 5 for each category.ResultsTop knowledge gaps include the accuracy of automated OHCA detection technologies and the feasibility and reliability of automated EMS activation. The main barriers to translation are the risk of false positives potentially overburdening EMS, development and application costs of technology and the challenge of integrating new technology in EMS IT systems. The top research priorities are large-scale evaluation studies to measure real world performance and user research regarding the willingness to adopt these technologies.ConclusionAutomated cardiac arrest diagnosis has the potential to significantly impact time to resuscitation and survival of OHCA because it could convert unwitnessed events into witnessed events. Validation and feasibility studies are needed. The specificity of the technology must be high not to overburden limited EMS resources. If adequate event classification is achieved, future research could shift toward event prediction, focusing on identifying potential digital biomarkers and signatures of imminent cardiac arrest. Implementation could be challenging due to high costs of development, regulatory considerations and instantiation logistics.
Project description:IntroductionAmplifying lay-rescuer response is a key priority to increase survival from out-of-hospital cardiac arrest (OHCA). We describe the current state of lay-rescuer response, how we envision the future, and the gaps, barriers, and research priorities that will amplify response to OHCA.Methods'Amplifying Lay-Rescuer Response' was one of six focus topics for the Wolf Creek XVII Conference held on June 14-17, 2023, in Ann Arbor, Michigan, USA. Conference invitees included international thought leaders and scientists in the field of cardiac arrest resuscitation from academia and industry. Participants submitted via online survey knowledge gaps, barriers to translation and research priorities for each focus topic. Expert panels used the survey results and their own perspectives and insights to create and present a preliminary unranked list for each category that was debated, revised and ranked by all attendees to identify the top 5 for each category.ResultsThe top five knowledge gaps as ranked by the panel, reflected a recognition of the need to better understand the psycho-social aspects of lay response. The top five barriers to translation reflected issues at the individual, community, societal, structural, and governmental levels. The top five research priorities were focused on understanding the social/psychological and emotional barriers to action, finding the most effective/cost-effective strategies to educate lay persons and implement community life-saving interventions, evaluation of new technological solutions and how to enhance the role of dispatch working with lay-rescuers.ConclusionFuture research in lay rescuer response should incorporate technology innovations, understand the "humanity" of the situation, leverage implementation science and systems thinking to save lives. This will require the field of resuscitation to engage with scholars outside our traditional ranks and to be open to new ways of thinking about old problems.
Project description:BP180 is a type II collagenous transmembrane protein and is best known as the major autoantigen in the blistering skin disease bullous pemphigoid (BP). The BP180 trimer is a central component in type I hemidesmosomes (HD), which cause the adhesion between epidermal keratinocytes and the basal lamina, but BP180 is also expressed in several non-HD locations, where its functions are poorly characterized. The immunological roles of intact and proteolytically processed BP180, relevant in BP, have been subject to intensive research, but novel functions in cell proliferation, differentiation, and aging have also recently been described. To better understand the multiple physiological functions of BP180, the focus should return to the protein itself. Here, we comprehensively review the properties of the BP180 molecule, present new data on the biochemical features of its intracellular domain, and discuss their significance with regard to BP180 folding and protein-protein interactions.
Project description:As part of the ENCODE consortium, the GENCODE project is producing a reference gene set through manual and automated gene prediction. Selected transcript models are verified experimentally by RT-PCR amplification of at least one of their unique splice junctions, followed by high-throughput sequencing (RT-PCR-seq). The experimental targets are manually annotated transcripts with novel or putative status, non-pseudogene biotype, and unique splice junctions which have not been validated previously and are not supported by RNAseq data from the ENCODE and GTEx projects. For Batch XVII, 1159 splice junctions which failed this experimental verification in previous experiments were tested again. On this occasion, newly designed PCR primers were used and compared with the original ones. In addition, the original tissue panel was widened with the inclusion of eight new tissues.
Project description:Collagen XVII (COL17) is a hemidesmosomal transmembrane protein in the skin, which, in several autoimmune blistering skin diseases, may be targeted by autoantibodies. In addition, loss-of-function mutations in the COL17A1 gene induce a subtype of junctional epidermolysis bullosa. The extracellular domain of COL17 can be physiologically cleaved from the cell surface by ADAM family proteins in a process known as ectodomain shedding. COL17 ectodomain shedding is thought to be associated with the migration and proliferation of keratinocytes. Furthermore, the C-terminal cleavage of COL17 may be associated with basement membrane formation. COL17 can be targeted by various proteases, including MMP9, neutrophil elastase, plasmin and granzyme B, which may be associated with blister formation in pemphigoid diseases. Interestingly, cleavage of COL17 may induce neoepitopes on the proteolysed fragments, and such induction is associated with dynamic structural changes. This review summarizes the current understanding of cleavage of COL17, and how such cleavage relates to blistering skin diseases.
Project description:We used the mummichog (Fundulus heteroclitus) array we developed to test whether our arrays could be used to monitor the efficacy of remediation at an estuarine Superfund site. Shipyard Creek is a chromium-contaminated Superfund site in Charleston, SC undergoing remediation, therefore it provides a unique opportunity to study the efficacy of arrays as a molecular biomarker in of toxicant effects in mummichogs. Mummichogs were captured in Shipyard Creek in Charleston, SC prior to remediation (2000), after remediation began (2003), and as remediation further progressed (2005). Simultaneously, mummichogs were collected from a reference site at the Winyah-Bay National Estuarine Research Reserve (NERR). The hepatic gene expression pattern of fish captured at Shipyard Creek showed wide differences from the fish captured at NERR in 2000. As remediation progressed the gene expression pattern of fish captured at Shipyard Creek became increasingly similar to fish captured at NERR, and the number of genes differently expressed dropped from 22 to 4. The magnitude of differential gene expression of the individual genes also decreased during remediation. The recovering gene expression profile is associated with lower chromium bioavailability, demonstrated through significantly decreased body burden and sediment concentrations. For example, sediment concentrations at Shipyard Creek were 80-fold greater than NERR in 2000, 51-fold greater in 2003, and only 8-fold greater in 2005. However, hydraulic dredging in 2005 stirred up the sediments and increased body burden of chromium even though chromium sediment concentrations continued to drop. Therefore, the number of differentially expressed genes increased to 9. Overall, the data supports our hypothesis that arrays can be used to monitor site mitigation, as the number of genes differentially expressed mimics the body burden and also indicates when on-site remediation is increasing bioavailability. Keywords: Field site