Leadership Observation and Feedback Tool: A Novel Instrument for Assessment of Clinical Leadership Skills.

BACKGROUND: While leadership training is increasingly incorporated into residency education, existing assessment tools to provide feedback on leadership skills are only applicable in limited contexts. OBJECTIVE: We developed an instrument, the Leadership Observation and Feedback Tool (LOFT), for assessing clinical leadership. METHODS: We used an iterative process to develop the tool, beginning with adapting the Leadership Practices Inventory to create an open-ended survey for identification of clinical leadership behaviors. We presented these to leadership experts who defined essential behaviors through a modified Delphi approach. In May 2014 we tested the resulting 29-item tool among residents in the internal medicine and pediatrics departments at 2 academic medical centers. We analyzed instrument performance using Cronbach's alpha, interrater reliability using intraclass correlation coefficients (ICCs), and item performance using linear-by-linear test comparisons of responses by postgraduate year, site, and specialty. RESULTS: A total of 377 (of 526, 72%) team members completed the LOFT for 95 (of 519, 18%) residents. Overall ratings were high-only 14% scored at the novice level. Cronbach's alpha was 0.79, and the ICC ranged from 0.20 to 0.79. Linear-by-linear test comparisons revealed significant differences between postgraduate year groups for some items, but no significant differences by site or specialty. Acceptability and usefulness ratings by respondents were high. CONCLUSIONS: Despite a rigorous approach to instrument design, we were unable to collect convincing validity evidence for our instrument. The tool may still have some usefulness for providing formative feedback to residents on their clinical leadership skills.

The Effect of Laser Fiber Cleave Technique and Lithotripsy Time on Power Output.

PURPOSE: Various cleave techniques have recently been shown to significantly impact initial laser fiber power output during holmium laser lithotripsy. The impact of cleave technique on long-term power output has not been well characterized. The purpose of this study was to determine the effect of laser cleave technique on power output over time. MATERIALS AND METHODS: In this randomized single-blinded study, five cleave techniques were tested on two holmium laser fiber diameters (200, 365 µm) over 15 minutes of laser lithotripsy with calcium oxalate monohydrate stones. Comparisons between cleave techniques and fiber diameters were performed using independent samples Mann-Whitney U, Kruskal-Wallis, and homogeneity of variance tests with a significance of p < 0.05. RESULTS: The 365-µm fiber was more durable and less affected by burnback degradation than the 200-µm fiber (p < 0.05). While initial power output varied between cleave techniques, all significance disappeared by 3 minutes. Power output decreased rapidly by a mean of 0.62 W over 4 minutes (p < 0.05), following which there was no significant change. CONCLUSION: These findings confirm that initial laser fiber power output is significantly influenced by cleave technique, and the ceramic scissor is the optimal tool for cleaving between procedures. However, because of rapid fiber tip degradation and power loss, this study argues against routine cleaving to improve procedural efficiency in lengthy ureteroscopy cases.

Micropillar arrays as a high-throughput screening platform for therapeutics in multiple sclerosis.

Functional screening for compounds that promote remyelination represents a major hurdle in the development of rational therapeutics for multiple sclerosis. Screening for remyelination is problematic, as myelination requires the presence of axons. Standard methods do not resolve cell-autonomous effects and are not suited for high-throughput formats. Here we describe a binary indicant for myelination using micropillar arrays (BIMA). Engineered with conical dimensions, micropillars permit resolution of the extent and length of membrane wrapping from a single two-dimensional image. Confocal imaging acquired from the base to the tip of the pillars allows for detection of concentric wrapping observed as 'rings' of myelin. The platform is formatted in 96-well plates, amenable to semiautomated random acquisition and automated detection and quantification. Upon screening 1,000 bioactive molecules, we identified a cluster of antimuscarinic compounds that enhance oligodendrocyte differentiation and remyelination. Our findings demonstrate a new high-throughput screening platform for potential regenerative therapeutics in multiple sclerosis.

A cell-permeable hairpin peptide inhibits hepatitis C viral nonstructural protein 5A-mediated translation and virus production.

UNLABELLED: NS5A is a key regulator of the hepatitis C virus (HCV) life cycle including RNA replication, assembly, and translation. We and others have shown that NS5A augments HCV internal ribosomal entry site (IRES)-mediated translation. Furthermore, Quercetin treatment and heat shock protein (HSP) 70 knockdown inhibit the NS5A-driven augmentation of IRES-mediated translation and infectious virus production. We have also coimmunoprecipitated HSP70 with NS5A and demonstrated cellular colocalization, leading to the hypothesis that the NS5A/HSP70 complex formation is important for IRES-mediated translation. Here, we have identified the NS5A region responsible for complex formation through in vitro deletion analyses. Deletion of NS5A domains II and III failed to reduce HSP70 binding, whereas domain I deletion eliminated complex formation. NS5A domain I alone also bound HSP70. Deletion mapping of domain I identified the C-terminal 34 amino acids (C34) as the interaction site. Furthermore, addition of C34 to domains II and III restored complex formation. C34 expression significantly reduced intracellular viral protein levels, in contrast to same-size control peptides from other NS5A domains. C34 also competitively inhibited NS5A-augmented IRES-mediated translation, whereas controls did not. Triple-alanine scan mutagenesis determined that an exposed beta-sheet hairpin in C34 was primarily responsible for NS5A-augmented IRES-mediated translation. Moreover, treatment with a 10-amino acid peptide derivative of C34 suppressed NS5A-augmented IRES-mediated translation and significantly inhibited intracellular viral protein synthesis, with no associated cytotoxicity. CONCLUSION: These results support the hypothesis that the NS5A/HSP70 complex augments viral IRES-mediated translation, identify a sequence-specific hairpin element in NS5A responsible for complex formation, and demonstrate the functional significance of C34 hairpin-mediated NS5A/HSP70 interaction. Identification of this element may allow for further interrogation of NS5A-mediated IRES activity, sequence-specific HSP recognition, and rational drug design. (HEPATOLOGY 2012;55:1662-1672).