Regional Thoracic Surgery Quality Collaboration Formation: Providence Thoracic Surgery Initiative.

BACKGROUND: Surgery quality initiatives improve clinical outcomes in cardiac and general surgery. No mature thoracic surgery (TS) regional effort has been described. METHODS: An intramural grant funded the Thoracic Surgery Initiative (TSI). Using professional organization, site specific administrative and clinical databases, surgeons performing TS across a large western health system were identified. Participants were recruited through stakeholder surveys, personal contact and meetings. Differences in practices and outcomes were identified. 14 centers performing TS in 5 states formed the TSI with a mission to define, implement and monitor TS quality. RESULTS: A TS data system based on Society of Thoracic Surgeons General TS Database was implemented. 2015/2016 clinical data revealed significant differences in outcomes. Clinical data allows quality implementation including identification and propagation of internal best practices and monitoring. TS practice standardization was agreed to using predefined TS best practice components that were incorporated into standardized TS care documents. Standardized care document completion by providers was intended to provoke desired TS care. The standardized care documents reside on the system wide electronic health record. Using literature and substantial surgeon experience, standardized TS care pathways for important or common clinical scenarios were developed (pneumonectomy, primary spontaneous pneumothorax, etc). The TSI internet site serves as a harbor for standardization products. CONCLUSIONS: The TSI is evolving. Surgeon engagement remains high. The TSI enabled surgeons to lead, set the agenda and remain in control of our destiny. Indeed, health care cannot appropriately evolve without such physician vision, engagement and leadership

Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy

Preclinical studies and initial clinical trials have documented the feasibility of adenoassociated virus (AAV)–mediated gene therapy for hemophilia B. In an 8-year study, inhibitor-prone hemophilia B dogs (n = 2) treated with liver-directed AAV2 factor IX (FIX) gene therapy did not have a single bleed requiring FIX replacement, whereas dogs undergoing muscle-directed gene therapy (n = 3) had a bleed frequency similar to untreated FIX-deficient dogs. Coagulation tests (whole blood clotting time [WBCT], activated clotting time [ACT], and activated partial thromboplastin time [aPTT]) have remained at the upper limits of the normal ranges in the 2 dogs that received liver-directed gene therapy. The FIX activity has remained stable between 4% and 10% in both liver-treated dogs, but is undetectable in the dogs undergoing muscle-directed gene transfer. Integration site analysis by linear amplification–mediated polymerase chain reaction (LAM-PCR) suggested the vector sequences have persisted predominantly in extrachromosomal form. Complete blood count (CBC), serum chemistries, bile acid profile, hepatic magnetic resonance imaging (MRI) and computed tomography (CT) scans, and liver biopsy were normal with no evidence for tumor formation. AAV-mediated liver-directed gene therapy corrected the hemophilia phenotype without toxicity or inhibitor development in the inhibitor-prone null mutation dogs for more than 8 years

GHOST Commissioning Science Results: Identifying a New Chemically Peculiar Star in Reticulum II

The Gemini High-resolution Optical SpecTrograph (GHOST) is the newest high-resolution spectrograph to be developed for a large-aperture telescope, recently deployed and commissioned at the Gemini-South telescope. In this paper, we present the first science results from the GHOST spectrograph taking during its commissioning runs. We have observed the bright metal-poor benchmark star HD 122563, along with two stars in the ultrafaint dwarf galaxy Reticulum II (Ret ii ), one of which was previously identified as a candidate member, but did not have a previous detailed chemical abundance analysis. We find that this candidate (GDR3 0928) to be a bona fide member of Ret ii , and from a spectral synthesis analysis it is also revealed to be a CEMP- r star, with significant enhancements in several light elements (C, N, O, Na, Mg, and Si), in addition to featuring an r -process enhancement like many other Ret ii stars. The light-element enhancements in this star resemble the abundance patterns seen in the CEMP-no stars of other ultrafaint dwarf galaxies, and are thought to have been produced by an independent source from the r -process. These unusual abundance patterns are thought to be produced by faint supernovae, which may be produced by some of the earliest generations of stars

Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p<0·0055 (for rs2305480_G, odds ratio [OR] 1·36 [95% CI 1·12–1·65], p=0·0014; and for rs8076131_A, OR 1·37 [1·13–1·67], p=0·0010). In upper airway epithelial cells from African American children, genotype at rs2305480 was the most significant eQTL for GSDMB (eQTL effect size [β] 1·35 [95% CI 1·25–1·46], p<0·0001), and to a lesser extent showed an eQTL effect for post-GPI attachment to proteins phospholipase 3 (β 1·15 [1·08–1·22], p<0·0001). No SNPs were eQTLs for ORMDL3. By contrast, in PBMCs, the five core SNPs were associated only with expression of GSDMB and ORMDL3. Genotype at rs12936231 (in zona pellucida binding protein 2) showed the strongest associations across both genes (for GSDMB, eQTLβ 1·24 [1·15–1·32], p<0·0001; and for ORMDL3 (β 1·19 [1·12–1·24], p<0·0001). The eQTL effects of rs2305480 on GSDMB expression were replicated in lower airway cells from African American adults (β 1·29 [1·15–1·44], p<0·0001). Interpretation: Our study suggests that SNPs regulating GSDMB expression in airway epithelial cells have a major role in childhood-onset asthma, whereas SNPs regulating the expression levels of 17q12–21 genes in resting blood cells are not central to asthma risk. Our genetic and gene expression data in African Americans and European Americans indicated GSDMB to be the leading candidate gene at this important asthma locus.6 month embargo; published: 01 May 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]