Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV

Training Residents in High-Value, Cost-Effective Care: a National Survey of Psychiatry Program Directors

OBJECTIVE: The goal of this study was to explore how prepared psychiatry programs are to teach residents to practice resource management and high-value, cost-effective care. METHODS: An anonymous online survey was sent to 187 psychiatry training directors between July and September 2015. RESULTS: Forty-four percent of training directors responded to the survey. While most training directors who responded (88%) agreed that that graduate medical education has a responsibility to respond to the rising cost of health care, fewer than half agreed that that their faculty members consistently model cost-effective care (48%), that residents have access to information regarding the cost of tests and procedures (32%), and that residents are prepared to integrate the cost of care with available evidence when making medical decisions (44%). Only 11% reported providing training in resource management. Barriers cited to teaching cost-effective care included a lack of information regarding health care costs (45%), a lack of time (24%), a lack of faculty with relevant skills (19%), and competing training demands and priorities (18%). Training directors also noted a lack of available curricular resources and assessment tools (21%). Another 12% cited concerns about cost containment overriding treatment guidelines. Ninety percent of training directors agreed that they would be interested in resources to help teach high-value, cost-effective care. CONCLUSIONS: Most psychiatry programs do not provide formal training in resource management but are interested in resources to teach high-value, cost-effective care. Curricula for residents and faculty may help meet this need