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PURPOSE To determine the usefulness of a comprehensive, targeted-capture next-generation sequencing (NGS) assay for the clinical management of children undergoing enucleation for retinoblastoma. DESIGN Cohort study. GF120918 molecular weight PARTICIPANTS Thirty-two children with retinoblastoma. METHODS We performed targeted NGS using the UCSF500 Cancer Panel (University of California, San Francisco, San Francisco, CA) on formalin-fixed, paraffin-embedded tumor tissue along with constitutional DNA isolated from peripheral blood, buccal swab, or uninvolved optic nerve. Peripheral blood samples were also sent to a commercial laboratory for germline RB1 mutation testing. MAIN OUTCOME MEASURES Presence or absence of germline RB1 mutation or deletion, tumor genetic profile, and association of genetic alterations with clinicopathologic features. RESULTS Germline mutation or deletion of the RB1 gene was identified in all children with bilateral retinoblastoma (n = 12), and these NGS results were 100% concordant with commercial germline RB1 mutation analysis. In tumor tissue tested with NGS, biallelic inactivation of RB1 was identified in 28 tumors and focal MYCN amplification was identified in 4 tumors (2 with wild-type RB1 and 2 with biallelic RB1 inactivation). Additional likely pathogenic alterations beyond RB1 were identified in 13 tumors (41%), several of which have not been reported previously in retinoblastoma. These included focal amplifications of MDM4 and RAF1, as well as damaging mutations involving BCOR, ARID1A, MGA, FAT1, and ATRX. The presence of additional likely pathogenetic mutations beyond RB1 inactivation was associated with aggressive histopathologic features, including higher histologic grade and anaplasia, and also with both unilateral and sporadic disease. CONCLUSIONS Comprehensive NGS analysis reliably detects relevant mutations, amplifications, and chromosomal copy number changes in retinoblastoma. The presence of genetic alterations beyond RB1 inactivation correlates with aggressive histopathologic features. The main purpose of this review is to highlight mitochondria as a new therapeutic target to prevent bronchial smooth muscle (BSM) remodeling in asthma. Severe asthmatic patients, representing 5-10% of all asthmatics, are characterized by an increased BSM mass which is highly correlated with the severity of the disease and the rate of exacerbations. None of the current asthma therapies are effective in reducing BSM remodelling. This review, based on the current literature, reports the role of mitochondria in BSM, particularly in calcium signaling. BACKGROUND Medical student procedural participation is increasingly limited, creating concerns over poor preparation for internship. Inadequate experiences may also compromise patient safety. This study explores variances in procedural entrustment of medical students between core clerkships during the first clinical year. METHODS Students completing their first clinical year were surveyed on procedure participation. Holistic entrustment decisions are complex, thus participation was used as an objective proxy for entrustment. RESULTS 138 students responded (66% response rate); 89% (123/138) wished they had performed more procedures. Students had higher participation rates during procedural clerkships (surgery, obstetrics/gynecology). Entrustment was highest during surgery, and lowest during pediatrics. Surgery gave statistically significantly higher entrustment for subcuticular suturing (compared to obstetrics/gynecology) and nasogastric tube removal (compared to internal medicine). Entrustment was generally inversely proportional to procedure complexity within each specialty. CONCLUSIONS Students encounter higher entrustment during procedural clerkships, especially surgery. Targeted areas for increased procedural involvement can be identified in all specialties. INTRODUCTION Teaching assistant (TA) cases allow senior residents (SR) to gain autonomy. We compared the safety profiles of TA cases performed under direct vs. indirect staff supervision. METHODS Prospective observational study of operative cases where a SR served as the TA between 7/2014-6/2017 (n = 161). Patient/operative characteristics, 30-day outcomes, and SR survey data were compared by level of supervision. RESULTS Case mix included 68 laparoscopic appendectomies (42%), 49 laparoscopic cholecystectomies (30%), 10 I&Ds (6%), 10 umbilical hernia repairs (6%), 4 port placements (3%), and 11 others. Indirectly supervised cases were shorter (61 vs. 76 min, p  less then  0.01), with less blood loss (11 vs. 24 ml, p  less then  0.05), and lower conversion rates (0% vs. 5.7%, p  less then  0.05). Perceived difficulty was high in 20% of cases with indirect vs. 49% with direct supervision (p  less then  0.01). Mean SR comfort was high (4.4 vs. 4.6 out of 5) regardless of level of staff supervision. 30-day complications did not differ for indirect vs. direct supervision (all p = NS). DISCUSSION Carefully selected TA cases offer SRs opportunities to practice autonomy without sacrificing operative time or patient safety. BACKGROUND Outpatient blood pressure variability (BPV) predicts hospitalization and death in non-surgical patients independently of hypertension. We hypothesized that preoperative BPV predicts postoperative outcomes. METHODS We assessed 22,233 veterans undergoing CABG, colectomy, hip replacement, pancreatectomy, carotid endarterectomy or AV-fistula with ≥10 outpatient BP’s over three preoperative years. Calculating BPV as SD of systolic or diastolic BP, we used logistic regression considering demographics, comorbidities, and pre-admission cardiovascular medications to estimate odds ratios for 90-day mortality or readmission, MI, CVA, renal failure, and wound infection, choosing the lowest 5%ile of systolic/diastolic BPV for reference. RESULTS Covariate-adjusted ORs for adverse outcomes increased as BPV increased. For instance, the highest 5%ile of systolic BPV had covariate-adjusted ORs of 2.96 and 1.78 for 90-day mortality and readmission. Systolic and diastolic BPV trended together but affected outcomes independently.