Publications

The limb is widely used as a model developmental system and changes to gene expression patterns in its signaling centers, notably the zone of polarizing activity (ZPA) and the apical ectodermal ridge (AER), are known to cause limb malformations and evolutionary differences in limb morphology. Although several genes that define these limb signaling centers have been described, the identification of regulatory elements that are active within these centers has been limited. By dissecting mouse E11.5 limbs that fluorescently mark the ZPA or AER, followed by fluorescence-activated cell sorting and low-cell H3K27ac ChIP-seq, we identified thousands of specific signaling-center enhancers. Our ChIP-seq datasets show strong correlation with ZPA- and AER-expressed genes, previously characterized functional ZPA and AER enhancers and enrichment for relevant biological terms related to limb development and malformation for the neighboring genes. Using transgenic assays, we show that several of these sequences function as ZPA and AER enhancers. Our results identify novel ZPA and AER enhancers that could be important regulators of genes involved in the establishment of these specialized regions and the patterning of tetrapod limbs.

OBJECTIVE

Systemic lupus erythematosus (SLE) has one of the highest hospital readmission rates among chronic conditions. This study was undertaken to identify patient-level, hospital-level, and geographic predictors of 30-day hospital readmissions associated with SLE.

METHODS

Using hospital discharge databases from 5 geographically dispersed states, we studied all-cause readmission of SLE patients between 2008 and 2009. We evaluated each hospitalization as a possible index event leading up to a readmission, our primary outcome. We accounted for clustering of hospitalizations within patients and within hospitals and adjusted for hospital case mix. Using multilevel mixed-effects logistic regression, we examined factors associated with 30-day readmission and calculated risk-standardized hospital-level and state-level readmission rates.

RESULTS

We examined 55,936 hospitalizations among 31,903 patients with SLE. Of these hospitalizations, 9,244 (16.5%) resulted in readmission within 30 days. In adjusted analyses, age was inversely related to risk of readmission. African American and Hispanic patients were more likely to be readmitted than white patients, as were those with Medicare or Medicaid insurance (versus private insurance). Several clinical characteristics of lupus, including nephritis, serositis, and thrombocytopenia, were associated with readmission. Readmission rates varied significantly between hospitals after accounting for patient-level clustering and hospital case mix. We also found geographic variation, with risk-adjusted readmission rates lower in New York and higher in Florida as compared to California.

CONCLUSION

We found that ~1 in 6 hospitalized patients with SLE were readmitted within 30 days of discharge, with higher rates among historically underserved populations. Significant geographic and hospital-level variation in risk-adjusted readmission rates suggests potential for quality improvement.