The effects of 17-β-estradiol in osteoblasts are primarily mediated by the nuclear transcription factors, estrogen receptor (ER)α and ERβ. ERs function through three general modes of action: DNA-binding dependent through estrogen response elements (EREs; designated nuclear ERE signaling); nuclear signaling via protein-protein interactions to other transcription factors (nuclear non-ERE signaling); and extra-nuclear signaling (membrane-bound functions of ERs). Identification of the specific transcriptional signatures regulated by each of these modes of action should contribute to an enhanced understanding of estrogen signaling in osteoblasts. To achieve this goal, we utilized specific mutations of ERα that eliminate the ability of the receptor to signal through a specific mode of action. The non-classical ERα knock-in (NERKI) mutation is incapable of signaling through direct DNA binding to EREs and the nuclear only ERα (NOER) mutation eliminates all membrane-localized signaling. Comparison of the gene expression patterns elicited by these mutations with the wild-type ERα (WT) pattern provides mode-specific data concerning transcriptional regulation by ERα. We expressed these constructs in the ER-negative osteoblastic cell line hFOB (-/+ estrogen) and performed global RNA-sequencing. Using a series of pair-wise comparisons, we generated three lists of genes that were regulated either by the nuclear ERE-dependent, nuclear ERE-independent, or extra-nuclear actions of ERα. Pathway and gene ontology analyses revealed that genes regulated through the nuclear ERE and nuclear non-ERE pathways were largely involved in transcriptional regulation, whereas genes regulated through extra-nuclear mechanisms are involved in cytoplasmic signaling transduction pathways. We also intersected our data with genes linked to bone density and fractures from a recent genome-wide association study and found 25 of 72 genes (35%) regulated by estrogen. These data provide a comprehensive list of genes and pathways targeted by these specific modes of ERα action and suggest that "mode-specific" ligands could be developed to modulate specific ERα functionality in bone.

Objectives

The objective was to determine whether a child's race or ethnicity as determined by the treating physician is independently associated with receiving abdominal computed tomography (CT) after blunt torso trauma.

Methods

We performed a planned secondary analysis of a prospective observational cohort of children < 18 years old presenting within 24 hours of blunt torso trauma to 20 North American emergency departments (EDs) participating in a pediatric research network, 2007-2010. Treating physicians documented race/ethnicity as white non-Hispanic, black non-Hispanic, or Hispanic. Using a previously derived clinical prediction rule, we classified each child's risk for having an intra-abdominal injury undergoing acute intervention to define injury severity. We performed multivariable analyses using generalized estimating equations to control for confounding and for clustering of children within hospitals.

Results

Among 12,044 enrolled patients, treating physicians documented race/ethnicity as white non-Hispanic (n = 5,847, 54.0%), black non-Hispanic (n = 3,687, 34.1%), or Hispanic of any race (n = 1,291, 11.9%). Overall, 51.8% of white non-Hispanic, 32.7% of black non-Hispanic, and 44.2% of Hispanic children underwent abdominal CT imaging. After age, sex, abdominal ultrasound use, risk for intra-abdominal injury undergoing acute intervention, and hospital clustering were adjusted for, the likelihood of receiving an abdominal CT was lower (odds ratio [OR] = 0.8, 95% confidence interval [CI] = 0.7 to 0.9) for black non-Hispanic than for white non-Hispanic children. For Hispanic children, the likelihood of receiving an abdominal CT did not differ from that observed in white non-Hispanic children (OR = 0.9, 95% CI = 0.8 to 1.1).

Conclusions

After blunt torso trauma, pediatric patients identified by the treating physicians as black non-Hispanic were less likely to receive abdominal CT imaging than those identified as white non-Hispanic. This suggests that nonclinical factors influence clinician decision-making regarding use of abdominal CT in children. Further studies should focus on explaining how patient race can affect provider choices regarding ED radiographic imaging.

Objective

To examine pediatric emergency department (ED) visits over 5 years, trends in injury severity, and associations between injury-related ED visit outcome and patient and community-level sociodemographic characteristics.

Study design

Retrospective analysis of administrative data provided to the Pediatric Emergency Care Applied Research Network Core Data Project, 2004-2008. Home addresses were geocoded to determine census block group and associated sociodemographic characteristics. Maximum Abbreviated Injury Scale severity and Severity Classification System scores were calculated. Generalized estimating equations were used to test for associations between sociodemographic characteristics and admission or transfer among injury-related ED visits.

Results

Overall ED visits and injury-related visits increased from 2004 to 2008 at study sites. Of 2,833676 successfully geocoded visits, 700,821 (24.7%) were injury-related. The proportion of higher severity injury-related visits remained consistent. Nearly 10% of injury-related visits resulted in admission or transfer each year. After adjusting for age, sex, payer, and injury severity, odds of admission or transfer were lower among minority children and children from areas with moderate and high prevalence of poverty.

Conclusions

Pediatric injury-related ED visits to included sites increased over the study period while injury severity, anticipated resource utilization, and visit outcomes remained stable, with low rates of admission or transfer. Sociodemographic differences in injury-related visits and ED disposition were apparent. ED-based injury surveillance is essential to understand disparities, inform targets for prevention programs, and reduce the overall burden of childhood injuries.