Publications

Type I neurofibromatosis (NF1) is caused by mutations in the NF1 gene encoding neurofibromin. Neurofibromin exhibits Ras GTPase activating protein (Ras-GAP) activity that is thought to mediate cellular functions relevant to disease phenotypes. Loss of murine Nf1 results in embryonic lethality due to heart defects, while mice with monoallelic loss of function mutations or with tissue-specific inactivation have been used to model NF1. Here, we characterize previously unappreciated phenotypes in Nf1-/- embryos, which are inhibition of hemogenic endothelial specification in the dorsal aorta, enhanced yolk sac hematopoiesis, and exuberant cardiac blood island formation. We show that a missense mutation engineered into the active site of the Ras-GAP domain is sufficient to reproduce ectopic blood island formation, cardiac defects, and overgrowth of neural crest-derived structures seen in Nf1-/-embryos. These findings demonstrate a role for Ras-GAP activity in suppressing the hemogenic potential of the heart and restricting growth of neural crest-derived tissues.

BACKGROUND

Older adults are the fastest growing segment of the United States population. There is an immediate need to identify novel, cost-effective community-based approaches that promote health and well-being for older adults, particularly those from diverse racial/ethnic and socioeconomic backgrounds. Because choral singing is multi-modal (requires cognitive, physical, and psychosocial engagement), it has the potential to improve health outcomes across several dimensions to help older adults remain active and independent. The purpose of this study is to examine the effect of a community choir program (Community of Voices) on health and well-being and to examine its costs and cost-effectiveness in a large sample of diverse, community-dwelling older adults.

METHOD/DESIGN

In this cluster randomized controlled trial, diverse adults age 60 and older were enrolled at Administration on Aging-supported senior centers and completed baseline assessments. The senior centers were randomly assigned to either start the choir immediately (intervention group) or wait 6 months to start (control). Community of Voices is a culturally tailored choir program delivered at the senior centers by professional music conductors that reflects three components of engagement (cognitive, physical, and psychosocial). We describe the nature of the study including the cluster randomized trial study design, sampling frame, sample size calculation, methods of recruitment and assessment, and primary and secondary outcomes.

DISCUSSION

The study involves conducting a randomized trial of an intervention as delivered in "real-world" settings. The choir program was designed using a novel translational approach that integrated evidence-based research on the benefits of singing for older adults, community best practices related to community choirs for older adults, and the perspective of the participating communities. The practicality and relatively low cost of the choir intervention means it can be incorporated into a variety of community settings and adapted to diverse cultures and languages. If successful, this program will be a practical and acceptable community-based approach for promoting health and well-being of older adults.

TRIAL REGISTRATION

ClinicalTrials.gov NCT01869179 registered 9 January 2013.

OBJECTIVE

To assess regional trends in long-term acute care hospital (LTAC) use over time.

DESIGN SETTING PARTICIPANTS

Retrospective study using 100% Texas Medicare data. Separate cohorts were created for each year from 2002-2011, which included all beneficiaries residing in 23 hospital referral regions (HRRs) with continuous enrollment in Parts A and B in the previous and current year, or until death.

MEASUREMENTS

LTAC utilization rate was defined as the number of individuals with a LTAC stay per 100,000 Medicare beneficiaries residing in the HRR. Baseline LTAC use at the HRR-level was categorized by tertiles of use in 2002.

RESULTS

Overall, LTAC use increased 35% from 2002-2011 and coincided with major Medicare policy changes. However, there were marked regional differences in LTAC utilization trends. From 2002-2011, HRRs in the lowest tertile of baseline LTAC use, which included regions with 0 to 1 LTAC facilities in 2002, had an increase in utilization by 211%, from 190 to 591 individuals per 100,000 persons. In contrast, HRRs in the highest tertile of baseline LTAC use, which included some of the most densely LTAC-bedded regions in the country, experienced a 21% decline (915 to 719 individuals per 100,000 persons; p<0.001 for interaction of LTAC utilization and tertile of baseline use).

CONCLUSION

These findings suggest substantial regional variation in the trends in LTAC use over time. Further research is needed to estimate how much of this variation is due to differences in clinical need due to increasing number of severely ill older adults versus regional market supply.