Quality Improvement in Pediatric Head Trauma with PECARN Rules Implementation as Computerized Decision Support

Background: For the 1.4 million emergency department (ED) visits for traumatic brain injury (TBI) annually in the United States, computed tomography (CT) may be over utilized. The Pediatric Emergency Care Applied Research Network developed 2 prediction rules to identify children at very low risk of clinically important TBI. We implemented these prediction rules as decision support within our electronic health record (EHR) to reduce CT. Objective: To test EHR decision support implementation in reducing CT rates for head trauma at 2 pediatric EDs. Methods: We compared monthly CT rates 1 year before [preimplementation (PRE)] and 1 year after [postimplementation (POST)] decision support implementation. The primary outcome was change in CT use rate over time, measured using statistical process control charts. Secondary analyses included multivariate comparisons of PRE to POST. Balancing measures included ED length of stay and returns within 7 days after ED release. Results: There were 2,878 patients with head trauma (1,329 PRE and 1,549 POST) included. Statistical process control charts confirmed decreased CT rates over time POST that was not present PRE. Secondary statistical analyses confirmed that CT scan utilization rates decreased from 26.8% to 18.9% (unadjusted Odds Ratio [OR], 0.64; 95% Confidence Interval [CI], 0.53 -0.76; adjusted OR, 0.71; 95% CI, 0.58 -0.86). Length of stay was unchanged. There was no increase in returns within 7 days and no significant missed diagnoses. Conclusions: Implementation of EHR-integrated decision support for children with head trauma presenting to the ED is associated with a decrease in CT utilization and no increase in significant safety events

Graph Neural Networks as Gradient Flows: understanding graph convolutions via energy

Gradient flows are differential equations that minimize an energy functional and constitute the main descriptors of physical systems. We apply this formalism to Graph Neural Networks (GNNs) to develop new frameworks for learning on graphs as well as provide a better theoretical understanding of existing ones. We derive GNNs as a gradient flow equation of a parametric energy that provides a physics-inspired interpretation of GNNs as learning particle dynamics in the feature space. In particular, we show that in graph convolutional models (GCN), the positive/negative eigenvalues of the channel mixing matrix correspond to attractive/repulsive forces between adjacent features. We rigorously prove how the channel-mixing can learn to steer the dynamics towards low or high frequencies, which allows to deal with heterophilic graphs. We show that the same class of energies is decreasing along a larger family of GNNs; albeit not gradient flows, they retain their inductive bias. We experimentally evaluate an instance of the gradient flow framework that is principled, more efficient than GCN, and achieves competitive performance on graph datasets of varying homophily often outperforming recent baselines specifically designed to target heterophily.Comment: First two authors equal contribution; 39 page

An ex vivo gene therapy approach to treat muscular dystrophy using inducible pluripotent stem cells.

Duchenne muscular dystrophy is a progressive and incurable neuromuscular disease caused by genetic and biochemical defects of the dystrophin-glycoprotein complex. Here we show the regenerative potential of myogenic progenitors derived from corrected dystrophic induced pluripotent stem cells generated from fibroblasts of mice lacking both dystrophin and utrophin. We correct the phenotype of dystrophic induced pluripotent stem cells using a Sleeping Beauty transposon system carrying the micro-utrophin gene, differentiate these cells into skeletal muscle progenitors and transplant them back into dystrophic mice. Engrafted muscles displayed large numbers of micro-utrophin-positive myofibers, with biochemically restored dystrophin-glycoprotein complex and improved contractile strength. The transplanted cells seed the satellite cell compartment, responded properly to injury and exhibit neuromuscular synapses. We also detect muscle engraftment after systemic delivery of these corrected progenitors. These results represent an important advance towards the future treatment of muscular dystrophies using genetically corrected autologous induced pluripotent stem cells

Relative importance of βcyto- and γcyto-actin in primary mouse embryonic fibroblasts

The highly homologous β (βcyto) and γ (γcyto) cytoplasmic actins are hypothesized to carry out both redundant and unique essential functions, but studies using targeted gene knockout and siRNA-mediated transcript knockdown to examine βcyto- and γcyto-isoform--specific functions in various cell types have yielded conflicting data. Here we quantitatively characterized actin transcript and protein levels, as well as cellular phenotypes, in both gene- and transcript-targeted primary mouse embryonic fibroblasts. We found that the smooth muscle αsm-actin isoform was the dominantly expressed actin isoform in WT primary fibroblasts and was also the most dramatically up-regulated in primary βcyto- or β/γcyto-actin double-knockout fibroblasts. Gene targeting of βcyto-actin, but not γcyto-actin, led to greatly decreased cell proliferation, decreased levels of cellular ATP, and increased serum response factor signaling in primary fibroblasts, whereas immortalization induced by SV40 large T antigen supported fibroblast proliferation in the absence of βcyto-actin. Consistent with in vivo gene-targeting studies in mice, both gene- and transcript-targeting approaches demonstrate that the loss of βcyto-actin protein is more disruptive to primary fibroblast function than is the loss of γcyto-actin

Near misses and unsafe conditions reported in a Pediatric Emergency Research Network

Objective Patient safety may be enhanced by using reports from front-line staff of near misses and unsafe conditions to identify latent safety events. We describe paediatric emergency department (ED) near-miss events and unsafe conditions from hospital reporting systems in a 1-year observational study from hospitals participating in the Pediatric Emergency Care Applied Research Network (PECARN). Design This is a secondary analysis of 1 year of incident reports (IRs) from 18 EDs in 2007–2008. Using a prior taxonomy and established method, this analysis is of all reports classified as near-miss (events not reaching the patient) or unsafe condition. Classification included type, severity, contributing factors and personnel involved. In-depth review of 20% of IRs was performed. Results 487 reports (16.8% of eligible IRs) are included. Most common were medication-related, followed by laboratory-related, radiology-related and process-related IRs. Human factors issues were related to 87% and equipment issues to 11%. Human factor issues related to non-compliance with procedures accounted for 66.4%, including 5.95% with no or incorrect ID. Handoff issues were important in 11.5%. Conclusions Medication and process-related issues are important causes of near miss and unsafe conditions in the network. Human factors issues were highly reported and non-compliance with established procedures was very common, and calculation issues, communications (ie, handoffs) and clinical judgment were also important. This work should enable us to help improve systems within the environment of the ED to enhance patient safety in the future

Pilot In-Trail Procedure Validation Simulation Study

A Human-In-The-Loop experiment was conducted at the National Aeronautics and Space Administration (NASA) Langley Research Center (LaRC) to investigate the viability of the In-Trail Procedure (ITP) concept from a flight crew perspective, by placing participating airline pilots in a simulated oceanic flight environment. The test subject pilots used new onboard avionics equipment that provided improved information about nearby traffic and enabled them, when specific criteria were met, to request an ITP flight level change referencing one or two nearby aircraft that might otherwise block the flight level change. The subject pilots subjective assessments of ITP validity and acceptability were measured via questionnaires and discussions, and their objective performance in appropriately selecting, requesting, and performing ITP flight level changes was evaluated for each simulated flight scenario. Objective performance and subjective workload assessment data from the experiment s test conditions were analyzed for statistical and operational significance and are reported in the paper. Based on these results, suggestions are made to further improve the ITP

The linked survival prospects of siblings : evidence for the Indian states

This paper reports an analysis of micro-data for India that shows a high correlation in infant mortality among siblings. In 13 of 15 states, we identify a causal effect of infant death on the risk of infant death of the subsequent sibling (a scarring effect), after controlling for mother-level heterogeneity. The scarring effects are large, the only other covariate with a similarly large effect being mother’s (secondary or higher) education. The two states in which evidence of scarring is weak are Punjab, the richest, and Kerala, the socially most progressive. The size of the scarring effect depends upon the sex of the previous child in three states, in a direction consistent with son-preference. Evidence of scarring implies that policies targeted at reducing infant mortality will have social multiplier effects by helping avoid the death of subsequent siblings. Comparison of other covariate effects across the states offers some interesting new insights

Onset of experimental severe cardiac fibrosis is mediated by overexpression of angiotensin-converting enzyme 2

Angiotensin-converting enzyme (ACE) 2 is a recently identified homologue of ACE. There is great interest in the therapeutic benefit for ACE2 overexpression in the heart. However, the role of ACE2 in the regulation of cardiac structure and function, as well as maintenance of systemic blood pressure, remains poorly understood. In cell culture, ACE2 overexpression led to markedly increased myocyte volume, assessed in primary rabbit myocytes. To assess ACE2 function in vivo, we used a recombinant adeno-associated virus 6 delivery system to provide 11-week overexpression of ACE2 in the myocardium of stroke-prone spontaneously hypertensive rats. ACE2, as well as the ACE inhibitor enalapril, significantly reduced systolic blood pressure. However, in the heart, ACE2 overexpression resulted in cardiac fibrosis, as assessed by histological analysis with concomitant deficits in ejection fraction and fractional shortening measured by echocardiography. Furthermore, global gene expression profiling demonstrated the activation of profibrotic pathways in the heart mediated by ACE2 gene delivery. This study demonstrates that sustained overexpression of ACE2 in the heart in vivo leads to the onset of severe fibrosis