Multi-centre implementation of an Educational program to improve the Cardiac Arrest diagnostic accuracy of ambulance Telecommunicators and survival outcomes for sudden cardiac arrest victims: the EduCATe study design and methodology.

BACKGROUND: Sudden cardiac death remains a leading cause of mortality in Canada, resulting in more than 35,000 deaths annually. Most cardiac arrest victims collapse in their own home (85% of the time) and 50% are witnessed by a family member or bystander. Survivors have a quality of life similar to the general population, but the overall survival rate for out-of-hospital cardiac arrest (OHCA) rarely exceeds 8%. Victims are almost four times more likely to survive when receiving bystander CPR, but bystander CPR rates have remained low in Canada over the past decade, not exceeding 15-25% until recently. Telecommunication-assisted CPR instructions have been shown to significantly increase bystander CPR rates, but agonal breathing may be misinterpreted as a sign of life by 9-1-1 callers and telecommunicators, and is responsible for as much as 50% of missed OHCA diagnoses. We sought to improve the ability and speed with which ambulance telecommunicators can recognize OHCA over the phone, initiate timely CPR instructions, and improve survival. METHODS: In this multi-center national study, we will implement and evaluate an educational program developed for ambulance telecommunicators using a multiple baseline interrupted time-series design. We will compare outcomes 12 months before and after the implementation of a 20-min theory-based educational video addressing barriers to recognition of OHCA while in the presence of agonal breathing. Participating Canadian sites demonstrated prior ability to collect standardized data on OHCA. Data will be collected from eligible 9-1-1 recordings, paramedic documentation and hospital medical records. Eligible cases will include suspected or confirmed OHCA of presumed cardiac origin in patients of any age with attempted resuscitation. DISCUSSION: The ability of telecommunication-assisted CPR instructions to improve bystander CPR and survival rates for OHCA victims is undeniable. The ability of telecommunicators to recognize OHCA over the phone is unequivocally impeded by relative lack of training on agonal breathing, and reluctance to initiate CPR instructions when in doubt. Our pilot data suggests the potential impact of this project will be to increase absolute OHCA recognition and bystander CPR rates by at least 10%, and absolute out-of-hospital cardiac arrest survival by 5% or more. TRIAL REGISTRATION: Prospectively registered on March 28, 2019 at ClinicalTrials.gov identifier: NCT03894059 .

Selection of DNA Aptamers for Root Exudate l-Serine Using Multiple Selection Strategies.

Agricultural biosensing can aid decisions about crop health and maintenance, because crops release root exudates that can inform about their status. l-Serine has been found to be indicative of nitrogen uptake in wheat and canola. The development of a biosensor for l-serine could allow farmers to monitor crop nutrient demands more precisely. The development of robust l-serine-binding DNA aptamers is described. Because small molecules can be challenging targets for Systematic Evolution of Ligands by EXponential enrichment (SELEX), three separate DNA libraries were used for SELEX experiments. A l-homocysteine aptamer was randomized to create a starting library for a l-serine selection (randomized SELEX). The final selection rounds of the l-homocysteine selection were also used as a starting library for l-serine (redirected SELEX). Finally, an original DNA library was used (original SELEX). All three SELEX experiments produced l-serine-binding aptamers with micromolar affinity, with Red.1 aptamer having a Kd of 7.9 ± 3.6 µM. Truncation improved the binding affinity to 5.2 ± 2.7 µM, and from this sequence, a Spiegelmer with improved nuclease resistance was created with a Kd of 2.0 ± 0.8 µM. This l-serine-binding Spiegelmer has the affinity and stability to be incorporated into aptamer-based biosensors for agricultural applications.

Microfluidic assay of the deformability of primitive erythroblasts.

Primitive erythroblasts (precursors of red blood cells) enter vascular circulation during the embryonic period and mature while circulating. As a result, primitive erythroblasts constantly experience significant hemodynamic shear stress. Shear-induced deformation of primitive erythroblasts however, is poorly studied. In this work, we examined the deformability of primitive erythroblasts at physiologically relevant flow conditions in microfluidic channels and identified the regulatory roles of the maturation stage of primitive erythroblasts and cytoskeletal protein 4.1 R in shear-induced cell deformation. The results showed that the maturation stage affected the deformability of primitive erythroblasts significantly and that primitive erythroblasts at later maturational stages exhibited a better deformability due to a matured cytoskeletal structure in the cell membrane.

Circulating primitive erythroblasts establish a functional, protein 4.1R-dependent cytoskeletal network prior to enucleating.

Hematopoietic ontogeny is characterized by distinct primitive and definitive erythroid lineages. Definitive erythroblasts mature and enucleate extravascularly and form a unique membrane skeleton, composed of spectrin, 4.1R-complex, and ankyrinR-complex components, to survive the vicissitudes of the adult circulation. However, little is known about the formation and composition of the membrane skeleton in primitive erythroblasts, which progressively mature while circulating in the embryonic bloodstream. We found that primary primitive erythroblasts express the major membrane skeleton genes present in similarly staged definitive erythroblasts, suggesting that the composition and formation of this membrane network is conserved in maturing primitive and definitive erythroblasts despite their respective intravascular and extravascular locations. Membrane deformability and stability of primitive erythroblasts, assayed by microfluidic studies and fluorescence imaged microdeformation, respectively, significantly increase prior to enucleation. These functional changes coincide with protein 4.1 R isoform switching and protein 4.1R-null primitive erythroblasts fail to establish normal membrane stability and deformability. We conclude that maturing primitive erythroblasts initially navigate the embryonic vasculature prior to establishing a deformable cytoskeleton, which is ultimately formed prior to enucleation. Formation of an erythroid-specific, protein 4.1R-dependent membrane skeleton is an important feature not only of definitive, but also of primitive, erythropoiesis in mammals.