The Acoustic Environment of the NASA Glenn 9- by 15-foot Low-Speed Wind Tunnel

The 9- by 15-Foot Low Speed Wind Tunnel is an acoustic testing facility with a long history of aircraft propulsion noise research. Due to interest in renovating the facility to support future testing of advanced quiet engine designs, a study was conducted to document the background noise level in the facility and investigate the sources of contaminating noise. The anechoic quality of the facility was also investigated using an interrupted noise method. The present report discusses these aspects of the noise environment in this facility

Acoustic Shielding for a Model Scale Counter-rotation Open Rotor

The noise shielding benefit of installing an open rotor above a simplified wing or tail is explored experimentally. The test results provide both a benchmark data set for validating shielding prediction tools and an opportunity for a system level evaluation of the noise reduction potential of propulsion noise shielding by an airframe component. A short barrier near the open rotor was found to provide up to 8.5 dB of attenuation at some directivity angles, with tonal sound particularly well shielded. Predictions from two simple shielding theories were found to overestimate the shielding benefit

Acoustic Methods Used in the NASA Glenn 9- by 15- Foot Low-Speed Wind Tunnel

The 9- by 15-Foot Low Speed Wind Tunnel has been used for acoustic testing for more than 40 years. The facility is principally used for testing aircraft engine propulsion components, for both aerodynamic performance and acoustics. The present report discusses the instrumentation and procedures currently used for the acquisition of high-quality acoustic data from aircraft engine fan models

Imputation-Based Analysis of Association Studies: Candidate Regions and Quantitative Traits

We introduce a new framework for the analysis of association studies, designed to allow untyped variants to be more effectively and directly tested for association with a phenotype. The idea is to combine knowledge on patterns of correlation among SNPs (e.g., from the International HapMap project or resequencing data in a candidate region of interest) with genotype data at tag SNPs collected on a phenotyped study sample, to estimate (“impute”) unmeasured genotypes, and then assess association between the phenotype and these estimated genotypes. Compared with standard single-SNP tests, this approach results in increased power to detect association, even in cases in which the causal variant is typed, with the greatest gain occurring when multiple causal variants are present. It also provides more interpretable explanations for observed associations, including assessing, for each SNP, the strength of the evidence that it (rather than another correlated SNP) is causal. Although we focus on association studies with quantitative phenotype and a relatively restricted region (e.g., a candidate gene), the framework is applicable and computationally practical for whole genome association studies. Methods described here are implemented in a software package, Bim-Bam, available from the Stephens Lab website http://stephenslab.uchicago.edu/software.html

Effect of AFT Rotor on the Inter-Rotor Flow of an Open Rotor Propulsion System

The effects of the aft rotor on the inter-rotor flow field of an open rotor propulsion rig were examined. A Particle Image Velocimetry (PIV) dataset that was acquired phase locked to the front rotor position has been phase averaged based on the relative phase angle between the forward and aft rotors. The aft rotor phase was determined by feature tracking in raw PIV images through an image processing algorithm. The effect of the aft rotor potential field on the inter-rotor flow were analyzed and shown to be in good agreement with Computational Fluid Dynamics (CFD) simulations. It was shown that the aft rotor had no substantial effect on the position of the forward rotor tip vortex but did have a small effect on the circulation strength of the vortex when the rotors were highly loaded

Advantages of the no-scalpel vasectomy technique

The no-scalpel vasectomy (NSV) technique should be used instead of the standard incisional method. (Strength of Recommendation: A, based on systematic reviews, mixed-quality randomized controlled trials [RCTs], cohort studies, and case-control series.) The NSV technique is associated with fewer complications, produces less perioperative and postoperative pain, results in quicker recovery, takes less time to perform, and is as effective as standard incisional vasectomy

Next generation sequencing of exceptional responders with BRAF-mutant melanoma: implications for sensitivity and resistance.

BackgroundPatients with BRAF mutation-positive advanced melanoma respond well to matched therapy with BRAF or MEK inhibitors, but often quickly develop resistance.MethodsTumor tissue from ten patients with advanced BRAF mutation-positive melanoma who achieved partial response (PR) or complete response (CR) on BRAF and/or MEK inhibitors was analyzed using next generation sequencing (NGS) assay. Genomic libraries were captured for 3230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to average median depth of 734X with 99% of bases covered >100X.ResultsThree of the ten patients (median number of prior therapies = 2) attained prolonged CR (duration = 23.6+ to 28.7+ months); seven patients achieved either a PR or a short-lived CR. One patient who achieved CR ongoing at 28.7+ months and had tissue available close to the time of initiating BRAF inhibitor therapy had only a BRAF mutation. Abnormalities in addition to BRAF mutation found in other patients included: mutations in NRAS, APC and NF1; amplifications in BRAF, aurora kinase A, MYC, MITF and MET; deletions in CDKN2A/B and PAX5; and, alterations in RB1 and ATM. Heterogeneity between patients and molecular evolution within patients was noted.ConclusionNGS identified potentially actionable DNA alterations that could account for resistance in patients with BRAF mutation-positive advanced melanoma who achieved a PR or CR but whose tumors later progressed. A subset of patients with advanced melanoma may harbor only a BRAF mutation and achieve a durable CR on BRAF pathway inhibitors

A programme for risk assessment and minimisation of progressive multifocal leukoencephalopathy developed for vedolizumab clinical trials

Introduction Over the past decade, the potential for drug-associated progressive multifocal leukoencephalopathy (PML) has become an increasingly important consideration in certain drug development programmes, particularly those of immunomodulatory biologics. Whether the risk of PML with an investigational agent is proven (e.g. extrapolated from relevant experience, such as a class effect) or merely theoretical, the serious consequences of acquiring PML require careful risk minimisation and assessment. No single standard for such risk minimisation exists. Vedolizumab is a recently developed monoclonal antibody to α4β7 integrin. Its clinical development necessitated a dedicated PML risk minimisation assessment as part of a global preapproval regulatory requirement. Objective The aim of this study was to describe the multiple risk minimisation elements that were incorporated in vedolizumab clinical trials in inflammatory bowel disease patients as part of the risk assessment and minimisation of PML programme for vedolizumab. Methods A case evaluation algorithm was developed for sequential screening and diagnostic evaluation of subjects who met criteria that indicated a clinical suspicion of PML. An Independent Adjudication Committee provided an independent, unbiased opinion regarding the likelihood of PML. Results Although no cases were detected, all suspected PML events were thoroughly reviewed and successfully adjudicated, making it unlikely that cases were missed. Conclusion We suggest that this programme could serve as a model for pragmatic screening for PML during the clinical development of new drugs