Patient Safety Training in Pediatric Emergency Medicine: A National Survey of Program Directors

Objectives The Accreditation Council for Graduate Medical Education requires training in patient safety and medical errors but does not provide specification for content or methods. Pediatric emergency medicine ( EM ) fellowship directors were surveyed to characterize current training of pediatric EM fellows in patient safety and to determine the need for additional training. Methods From June 2013 to August 2013, pediatric EM fellowship directors were surveyed via e‐mail. Results Of the 71 eligible survey respondents, 57 (80.3%) completed surveys. A formal curriculum was present in 24.6% of programs, with a median of 6 hours (range = 1 to 18 hours) dedicated to the curriculum. One program evaluated the efficacy of the curriculum. Nearly 91% of respondents without formal programs identified lack of local faculty expertise or interest as the primary barrier to implementing patient safety curricula. Of programs without formal curricula, 93.6% included at least one component of patient safety training in their fellowship programs. The majority of respondents would implement a standardized patient safety curriculum for pediatric EM if one was available. Conclusions Despite the importance of patient safety training and requirements to train pediatric EM fellows in patient safety and medical errors, there is a lack of formal curriculum and local faculty expertise. The majority of programs have introduced components of patient safety training and desire a standardized curriculum. Resumen Objetivos El Accreditation Council for Graduate Medical Education exige formación en seguridad del paciente y errores médicos, pero no proporciona especificaciones de los contenidos o los métodos. Se encuestó a los directores del programa de posresidencia en Medicina de Urgencias y Emergencias ( MUE ) Pediátrica para caracterizar acerca de la formación actual de los adjuntos de MUE Pediátrica en seguridad del paciente, para intentar determinar la necesidad de formación adicional. Metodología Se encuestó mediante correo electrónico a los directores del programa de posresidencia de MUE Pediátrica de junio de 2013 a agosto de 2013. Resultados De los 71 respondedores elegibles de la encuesta, 57 (80,3%) la completaron. Existía un plan de estudios formal en un 24,6% de los programas, con una mediana de 6 horas (rango de 1 a 18 horas) dedicadas en el plan de estudios. Un programa evaluó la eficacia del plan de formación. Casi un 91% de los respondedores sin un programa formal identificó una falta de experiencia o interés de los profesores locales como la barrera principal para implementar un plan de estudios sobre la seguridad del paciente. De los programas sin un plan de estudios formal, un 93,6% incluyó al menos un componente de formación en seguridad del paciente en su programa de posresidencia. La mayoría de los respondedores implementarían un plan de estudios estandarizado sobre seguridad del paciente en MUE Pediátrica si existiera alguno disponible. Conclusiones A pesar de la importancia de la formación en seguridad del paciente y los requisitos para formar a los adjuntos de MUE Pediátrica en seguridad del paciente y errores médicos, hay una falta de plan de estudios formal y de experiencia de profesores locales. La mayoría de los programas ha introducido componentes de formación en seguridad del paciente y desean un plan de estudios estandarizado.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108264/1/acem12418.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/108264/2/acem12418-sup-0001-DataSupplementS1.pd

Regulatory bioinformatics for food and drug safety

Abstract "Regulatory Bioinformatics" strives to develop and implement a standardized and transparent bioinformatic framework to support the implementation of existing and emerging technologies in regulatory decision-making. It has great potential to improve public health through the development and use of clinically important medical products and tools to manage the safety of the food supply. However, the application of regulatory bioinformatics also poses new challenges and requires new knowledge and skill sets. In the latest Global Coalition on Regulatory Science Research (GCRSR) governed conference, Global Summit on Regulatory Science (GSRS2015), regulatory bioinformatics principles were presented with respect to global trends, initiatives and case studies. The discussion revealed that datasets, analytical tools, skills and expertise are rapidly developing, in many cases via large international collaborative consortia. It also revealed that significant research is still required to realize the potential applications of regulatory bioinformatics. While there is significant excitement in the possibilities offered by precision medicine to enhance treatments of serious and/or complex diseases, there is a clear need for further development of mechanisms to securely store, curate and share data, integrate databases, and standardized quality control and data analysis procedures. A greater understanding of the biological significance of the data is also required to fully exploit vast datasets that are becoming available. The application of bioinformatics in the microbiological risk analysis paradigm is delivering clear benefits both for the investigation of food borne pathogens and for decision making on clinically important treatments. It is recognized that regulatory bioinformatics will have many beneficial applications by ensuring high quality data, validated tools and standardized processes, which will help inform the regulatory science community of the requirements necessary to ensure the safe introduction and effective use of these applications

Development of Translational Methods in Spectral Analysis of Human Infant Crying and Rat Pup Ultrasonic Vocalizations for Early Neurobehavioral Assessment

The purpose of this article is to describe the development of translational methods by which spectrum analysis of human infant crying and rat pup ultrasonic vocalizations (USVs) can be used to assess potentially adverse effects of various prenatal conditions on early neurobehavioral development. The study of human infant crying has resulted in a rich set of measures that has long been used to assess early neurobehavioral insult due to non-optimal prenatal environments, even among seemingly healthy newborn and young infants. In another domain of study, the analysis of rat put USVs has been conducted via paradigms that allow for better experimental control over correlated prenatal conditions that may confound findings and conclusions regarding the effects of specific prenatal experiences. The development of translational methods by which cry vocalizations of both species can be analyzed may provide the opportunity for findings from the two approaches of inquiry to inform one another through their respective strengths. To this end, we present an enhanced taxonomy of a novel set of common measures of cry vocalizations of both human infants and rat pups based on a conceptual framework that emphasizes infant crying as a graded and dynamic acoustic signal. This set includes latency to vocalization onset, duration and repetition rate of expiratory components, duration of inter-vocalization-intervals and spectral features of the sound, including the frequency and amplitude of the fundamental and dominant frequencies. We also present a new set of classifications of rat pup USV waveforms that include qualitative shifts in fundamental frequency, similar to the presence of qualitative shifts in fundamental frequency that have previously been related to insults to neurobehavioral integrity in human infants. Challenges to the development of translational analyses, including the use of different terminologies, methods of recording, and spectral analyses are discussed, as well as descriptions of automated processes, software solutions, and pitfalls

What is the function of mitochondrial networks? A theoretical assessment of hypotheses and proposal for future research

Mitochondria can change their shape from discrete isolated organelles to a large continuous reticulum. The cellular advantages underlying these fused networks are still incompletely understood. In this paper, we describe and compare hypotheses regarding the function of mitochondrial networks. We use mathematical and physical tools both to investigate existing hypotheses and to generate new ones, and we suggest experimental and modelling strategies. Among the novel insights we underline from this work are the possibilities that (i) selective mitophagy is not required for quality control because selective fusion is sufficient; (ii) increased connectivity may have non-linear effects on the diffusion rate of proteins; and (iii) fused networks can act to dampen biochemical fluctuations. We hope to convey to the reader that quantitative approaches can drive advances in the understanding of the physiological advantage of these morphological changes

Sudden Death in Pediatric Populations

Sudden death (SD) in children is rarer than in adults. In the pediatric population, SD accounts for less than one tenth of deaths from all causes. SD in infants is a separate entity commonly termed "sudden infant death syndrome (SIDS)". Previous studies on SD in pediatric patients primarily focused on infants and showed that the incidence of SIDS was much lower in Asian countries than in Western ones. However, these differences diminished after educational campaigns such as the back to sleep act in the late 1980s to early 1990s. The incidence of SIDS from Western reports has decreased from 2.69 to around 0.5-0.24 per 1,000 live births. Beyond infancy, the annual incidence of SD ranges from 1.3 to 7.5 per 100,000. In 2009, two population-based studies, one from Taiwan and the other from the US, explored the epidemiological profile of SD in children. The child health care indexes of these two countries are similar, but the annual incidence of pediatric SD was 7.5 and 2.7 per 100,000 in the USA and Taiwan, respectively. The implications of ethic-related differences requires further confirmation. Around 40% of pediatric SD could be from cardiac causes, either diagnosed or undiagnosed. Risk stratification for cardiac SD and patient selection for implantable cardioverter-defibrillator (ICD) therapy are recommended. However, the adoption of ICD as primary prevention for SD in children is still a challenging issue. Early detection of undiagnosed cardiac risk may be facilitated by cardiac screening either in newborns or the school-age population to better manage the risk of SD. However, the efficacy of such screening remains still controversial

Organelle tethering by a homotypic PDZ interaction underlies formation of the Golgi membrane network

Formation of the ribbon-like membrane network of the Golgi apparatus depends on GM130 and GRASP65, but the mechanism is unknown. We developed an in vivo organelle tethering assaying in which GRASP65 was targeted to the mitochondrial outer membrane either directly or via binding to GM130. Mitochondria bearing GRASP65 became tethered to one another, and this depended on a GRASP65 PDZ domain that was also required for GRASP65 self-interaction. Point mutation within the predicted binding groove of the GRASP65 PDZ domain blocked both tethering and, in a gene replacement assay, Golgi ribbon formation. Tethering also required proximate membrane anchoring of the PDZ domain, suggesting a mechanism that orientates the PDZ binding groove to favor interactions in trans. Thus, a homotypic PDZ interaction mediates organelle tethering in living cells

The making of a mammalian peroxisome, version 2.0: mitochondria get into the mix

This is the author accepted manuscript. The final version is available from Nature Publishing Group via the DOI in this record.A recent report from the laboratory of Heidi McBride (McGill University) presents a role for mitochondria in the de novo biogenesis of peroxisomes in mammalian cells (1). Peroxisomes are essential organelles responsible for a wide variety of biochemical functions, from the generation of bile, to plasmalogen synthesis, reduction of peroxides, and the oxidation of very long chain fatty acids (2). Like mitochondria, peroxisomes proliferate primarily through growth and division of pre-existing peroxisomes (3-6). However, unlike mitochondria, peroxisomes do not fuse (5,7); further, and perhaps most importantly, they can also be born de novo, a process thought to occur through the generation of pre-peroxisomal vesicles that originate from the endoplasmic reticulum (reviewed in (8,9). De novo peroxisome biogenesis has been extensively studies in yeast, with a major focus on the role of the ER in this process. Comprehensive studies in mammalian cells are, however, scarce (5,10-12). By exploiting patient cells lacking mature peroxisomes, Sugiura et al. (1) now assign a role to ER and mitochondria in de novo mammalian peroxisome biogenesis by showing that the formation of immature preperoxisomes occurs through the fusion of Pex3- / Pex14-containing mitochondriaderived vesicles with Pex16-containing ER-derived vesicles

Mitochondrial and Plasma Membrane Pools of Stomatin-Like Protein 2 Coalesce at the Immunological Synapse during T Cell Activation

Stomatin-like protein 2 (SLP-2) is a member of the stomatin – prohibitin – flotillin – HflC/K (SPFH) superfamily. Recent evidence indicates that SLP-2 is involved in the organization of cardiolipin-enriched microdomains in mitochondrial membranes and the regulation of mitochondrial biogenesis and function. In T cells, this role translates into enhanced T cell activation. Although the major pool of SLP-2 is associated with mitochondria, we show here that there is an additional pool of SLP-2 associated with the plasma membrane of T cells. Both plasma membrane-associated and mitochondria-associated pools of SLP-2 coalesce at the immunological synapse (IS) upon T cell activation. SLP-2 is not required for formation of IS nor for the re-localization of mitochondria to the IS because SLP-2-deficient T cells showed normal re-localization of these organelles in response to T cell activation. Interestingly, upon T cell activation, we found the surface pool of SLP-2 mostly excluded from the central supramolecular activation complex, and enriched in the peripheral area of the IS where signalling TCR microclusters are located. Based on these results, we propose that SLP-2 facilitates the compartmentalization not only of mitochondrial membranes but also of the plasma membrane into functional microdomains. In this latter location, SLP-2 may facilitate the optimal assembly of TCR signalosome components. Our data also suggest that there may be a net exchange of membrane material between mitochondria and plasma membrane, explaining the presence of some mitochondrial proteins in the plasma membrane

MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo

Erratum: https://link.springer.com/article/10.1007/s10863-014-9597-1MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1’s role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1−/− mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased α-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose oxidation. This is an factual error as written; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1−/− hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2’s regulation of mitochondrial function.Funding support from Medical Research Council, United Kingdom; National Institutes of Health, United States; British Heart Foundation, United Kingdo