GYPC encodes two erythrocyte surface sialoglycoproteins in humans, glycophorin C and glycophorin D (GPC and GPD), via initiation of translation at two start codons on a single transcript. The malaria-causing parasite Plasmodium falciparum uses GPC as a means of invasion into the human red blood cell. Here, we examine the molecular evolution of GYPC among the Hominoidea (Greater and Lesser Apes) and also the pattern of polymorphism at the locus in a global human sample. We find an excess of nonsynonymous divergence among species that appears to be caused solely by accelerated evolution of GYPC in the human lineage. Moreover, we find that the ability of GYPC to encode both GPC and GPD is a uniquely human trait, caused by the evolution of the GPC start codon in the human lineage. The pattern of polymorphism among humans is consistent with a hitchhiking event at the locus, suggesting that positive natural selection affected GYPC in the relatively recent past. Because GPC is exploited by P. falciparum for invasion of the red blood cell, we hypothesize that selection for evasion of P. falciparum has caused accelerated evolution of GYPC in humans (relative to other primates) and that this positive selection has continued to act in the recent evolution of our species. These data suggest that malaria has played a powerful role in shaping molecules on the surface of the human red blood cell. In addition, our examination of GYPC reveals a novel mechanism of protein evolution: co-option of untranslated region (UTR) sequence following the formation of a new start codon. In the case of human GYPC, the ancestral protein (GPD) continues to be produced through leaky translation. Because leaky translation is a widespread phenomenon among genes and organisms, we suggest that co-option of UTR sequence may be an important source of protein innovation.
CHD is the most commonly occurring birth defect in the United States. Improvements in supportive care for CHD result in increasing numbers of survivors who may develop benign or malignant conditions for which HSCT is indicated. However, the ability of individuals with CHD to tolerate HSCT is unknown. Retrospective medical record review of 1031 patients who underwent HSCT at Children's Hospital Boston between 1989 and 2007 identified those with CHD. Ten patients with CHD that required repair or palliation before or after HSCT, or with CHD that would have required repair had they survived HSCT, were identified. These patients tolerated chemotherapy and/or radiation therapy uneventfully. Although half experienced febrile neutropenia and two had documented bacteremia, no endocarditis was observed. During the first 100 days post-HSCT, combined rates of grade 3, 4, and 5 cardiac, renal, and pulmonary toxicity for these patients were 10%, 0%, and 10%, respectively. In children with underlying CHD, there was no clinical evidence of impaired ability to tolerate febrile neutropenia, volume challenge, or other regimen-related toxicities that might require significant cardiac reserve. CHD alone should not be considered an absolute contraindication for indicated HSCT.
Objective: Emergency department (ED) providers require competency in responding to hazardous materials (HAZMAT) events. The optimal strategies to teach HAZMAT response principles to ED providers and to ensure skill retention are not known. Our aim was to design, implement, and evaluate a multifaceted, interprofessional educational curriculum for pediatric ED staff to improve their skills, knowledge, and confidence in responding to a HAZMAT event.Methods: In this longitudinal cohort study, we created and assessed a 3-hour educational curriculum comprised of didactics, skills stations, a tabletop exercise, and a simulated multivictim disaster. Learning objectives included critical aspects of pediatric HAZMAT incident response with an emphasis on donning personal protective equipment (PPE). The primary outcome was the number of HAZMAT PPE donning steps correctly completed within 10 minutes at pre-and postcurriculum assessments measured using a 32-item checklist. Secondary outcomes included skill retention at 3 months, change in knowledge assessed using multiple-choice questions, and change in participant confidence.Results: Eighty-one of 84 participants (96%) completed the entire curriculum. Compared to the precurriculum assessment, participants completed more donning steps correctly after the intervention (mean increase = 58%, 95% confidence interval [CI] = 48%-70%). Relative to the baseline, more steps were also correctly completed at 3 months (mean increase = 49%, 95% CI = 38%-61%). Performance on multiple-choice knowledge questions and confidence in skills also significantly increased from the pre-to postcurriculum assessments. Conclusions:A newly developed HAZMAT educational curriculum improved skills-based performance, knowledge, and confidence in PPE and decontamination skills. Brief, multifaceted educational interventions for ED staff can effectively develop sustainable skills needed for uncommon emergency events.M ass casualty incidents in the emergency department (ED) setting are "high-stakes but low-frequency" events, 1 making training and retention of skills difficult. Response to events involving patient exposure to hazardous materials (HAZMAT) is an important part of ED disaster-preparedness protocols.
Study/Objective: This multinational study of the terminal year of high school students aims to explore the relationship between engaging in discussions about disasters, as primary outcome, and the entities best situated to deliver Disaster Risk Education (DRE), in addition to a series of independent predictors identified in previous research. Background: The aim of Disaster Reduction Education (DRE) is to achieve behavioral change. Over the past two decades, educational activities have been developed based on unverified assumptions, while the literature has not identified any significant change toward disaster preparedness at the individual level. Previous research suggests that change is dependent on multiple independent predictors. This study describes the relationship of the perceived entity responsible for disaster education, disaster education per se, sex, and country-specific characteristics with students discussing disasters with friends and family, as a measure of proactive behavioral change in disaster preparedness. School lessons and a national educational program are essential, but it's less clear which educational and delivery methods are best suited for DRE, which entities are best placed to engage with teenagers, and whether the assumptions that DRE can be learned like any other subject are true. Methods: A total of 3,829 final year high-school students participated in an international, multi-center prospective, crosssectional study using a validated questionnaire. Nine countries with different levels of disaster exposure, risk, and economic development were surveyed. Regression analyses examined the relationship between the likelihood of discussing disasters with friends and family and a series of independent variables. Results: While several independent predictors showed a significant main effect, DRE through school lessons in interaction with Family & Charity organizations had the highest predictive value. Conclusion: A behavioral change towards disaster preparedness in teenagers requires a synergistic partnership between different entities. DRE providers should engage with the entities with which the teenagers are more likely to collaborate, most and foremost, their families. Background: ED providers need competency in responding to HAZMAT events to treat contaminated patients, protect responding staff, and ensure the ED remains operational. The optimal strategy to teach HAZMAT response principles, including decontamination, to ED providers and to ensure the retention of these skills is not known.Methods: This is a prospective cohort study assessing an educational curriculum comprised of didactics, skills stations, a tabletop exercise, and simulation focused on critical aspects of pediatric HAZMAT incident response, with an emphasis on donning Personal Protective Equipment (PPE) and patient decontamination. All ED staff were eligible to participate, and participants were randomly assigned to dyads. The primary outcome was the number of HAZMAT PPE donning steps correctly, completed by each dyad ...
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