Validation of Prediction Rules for Computed Tomography Use in Children With Blunt Abdominal or Blunt Head Trauma: Protocol for a Prospective Multicenter Observational Cohort Study

BackgroundTraumatic brain injuries (TBIs) and intra-abdominal injuries (IAIs) are 2 leading causes of traumatic death and disability in children. To avoid missed or delayed diagnoses leading to increased morbidity, computed tomography (CT) is used liberally. However, the overuse of CT leads to inefficient care and radiation-induced malignancies. Therefore, to maximize precision and minimize the overuse of CT, the Pediatric Emergency Care Applied Research Network (PECARN) previously derived clinical prediction rules for identifying children at high risk and very low risk for IAIs undergoing acute intervention and clinically important TBIs after blunt trauma in large cohorts of children who are injured. ObjectiveThis study aimed to validate the IAI and age-based TBI clinical prediction rules for identifying children at high risk and very low risk for IAIs undergoing acute intervention and clinically important TBIs after blunt trauma. MethodsThis was a prospective 6-center observational study of children aged 24 hours for TBI, or hospital admission of ≥2 nights due to a TBI on CT). Prediction rule accuracy was assessed by measuring rule classification performance, using standard point and 95% CI estimates of the operational characteristics of each prediction rule (sensitivity, specificity, positive and negative predictive values, and diagnostic likelihood ratios). ResultsThe project was funded in 2016, and enrollment was completed on September 1, 2021. Data analyses are expected to be completed by December 2022, and the primary study results are expected to be submitted for publication in 2023. ConclusionsThis study will attempt to validate previously derived clinical prediction rules to accurately identify children at high and very low risk for clinically important IAIs and TBIs. Assuming successful validation, widespread implementation is then indicated, which will optimize the care of children who are injured by better aligning CT use with need. International Registered Report Identifier (IRRID)RR1-10.2196/4302

Restoring Regulatory T Cells in Type 1 Diabetes

Genetic and cellular studies of type 1 diabetes in patients and in the nonobese diabetic mouse model of type 1 diabetes point to an imbalance between effector T cells and regulatory T cells (Tregs) as a driver of the disease. The imbalance may arise as a consequence of genetically encoded defects in thymic deletion of islet antigen-specific T cells, induction of islet antigen-specific thymic Tregs, unfavorable tissue environment for peripheral Treg induction, and failure of islet antigen-specific Tregs to survive in the inflamed islets secondary to insufficient IL-2 signals. These understandings are the foundation for rationalized design of new therapeutic interventions to restore the balance by selectively targeting effector T cells and boosting Tregs

Different factors limit early‐ and late‐season windows of opportunity for monarch development

Abstract Seasonal windows of opportunity are intervals within a year that provide improved prospects for growth, survival, or reproduction. However, few studies have sufficient temporal resolution to examine how multiple factors combine to constrain the seasonal timing and extent of developmental opportunities. Here, we document seasonal changes in milkweed (Asclepias fascicularis)–monarch (Danaus plexippus) interactions with high resolution throughout the last three breeding seasons prior to a precipitous single‐year decline in the western monarch population. Our results show early‐ and late‐season windows of opportunity for monarch recruitment that were constrained by different combinations of factors. Early‐season windows of opportunity were characterized by high egg densities and low survival on a select subset of host plants, consistent with the hypothesis that early‐spring migrant female monarchs select earlier‐emerging plants to balance a seasonal trade‐off between increasing host plant quantity and decreasing host plant quality. Late‐season windows of opportunity were coincident with the initiation of host plant senescence, and caterpillar success was negatively correlated with heatwave exposure, consistent with the hypothesis that late‐season windows were constrained by plant defense traits and thermal stress. Throughout this study, climatic and microclimatic variations played a foundational role in the timing and success of monarch developmental windows by affecting bottom‐up, top‐down, and abiotic limitations. More exposed microclimates were associated with higher developmental success during cooler conditions, and more shaded microclimates were associated with higher developmental success during warmer conditions, suggesting that habitat heterogeneity could buffer the effects of climatic variation. Together, these findings show an important dimension of seasonal change in milkweed–monarch interactions and illustrate how different biotic and abiotic factors can limit the developmental success of monarchs across the breeding season. These results also suggest the potential for seasonal sequences of favorable or unfavorable conditions across the breeding range to strongly affect monarch population dynamics

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes