Definition ofthe Design Trajectory and Entry Flight Corridor for the NASA Orion Exploration Mission 1 Entry Trajectory Using an Integrated Approach and Optimization

One of the key design objectives of NASA's Orion Exploration Mission 1 (EM- 1) is to execute a guided entry trajectory demonstrating GN&C capability. The focus of this paper is defining the flyable entry corridor for EM-1 taking into account multiple subsystem constraints such as complex aerothermal heating constraints, aerothermal heating objectives, landing accuracy constraints, structural load limits, Human-System-Integration-Requirements, Service Module debris disposal limits and other flight test objectives. During the EM-1 Design Analysis Cycle 1 design challenges came up that made defining the flyable entry corridor for the EM-1 mission critical to mission success. This document details the optimization techniques that were explored to use with the 6-DOF ANTARES simulation to assist in defining the design entry interface state and entry corridor with respect to key flight test constraints and objectives

Randomized Trial of Interventions to Improve Childhood Asthma in Homes with Wood-Burning Stoves

BACKGROUND: Household air pollution due to biomass combustion for residential heating adversely affects vulnerable populations. Randomized controlled trials to improve indoor air quality in homes of children with asthma are limited, and no such studies have been conducted in homes using wood for heating. OBJECTIVES: Our aims were to test the hypothesis that household-level interventions, specifically improved-technology wood-burning appliances or air-filtration devices, would improve health measures, in particular Pediatric Asthma Quality of Life Questionnaire (PAQLQ) scores, relative to placebo, among children living with asthma in homes with wood-burning stoves. METHODS: A three-arm placebo-controlled randomized trial was conducted in homes with wood-burning stoves among children with asthma. Multiple preintervention and postintervention data included PAQLQ (primary outcome), peak expiratory flow (PEF) monitoring, diurnal peak flow variability (dPFV, an indicator of airway hyperreactivity) and indoor particulate matter (PM) PM2.5. RESULTS: Relative to placebo, neither the air filter nor the woodstove intervention showed improvement in quality-of-life measures. Among the secondary outcomes, dPFV showed a 4.1 percentage point decrease in variability [95% confidence interval (CI) = −7.8 to −0.4] for air-filtration use in comparison with placebo. The air-filter intervention showed a 67% (95% CI: 50% to 77%) reduction in indoor PM2.5, but no change was observed with the improved-technology woodstove intervention. CONCLUSIONS: Among children with asthma and chronic exposure to woodsmoke, an air-filter intervention that improved indoor air quality did not affect quality-of-life measures. Intent-to-treat analysis did show an improvement in the secondary measure of dPFV

Lattice Boltzmann simulations of soft matter systems

This article concerns numerical simulations of the dynamics of particles immersed in a continuum solvent. As prototypical systems, we consider colloidal dispersions of spherical particles and solutions of uncharged polymers. After a brief explanation of the concept of hydrodynamic interactions, we give a general overview over the various simulation methods that have been developed to cope with the resulting computational problems. We then focus on the approach we have developed, which couples a system of particles to a lattice Boltzmann model representing the solvent degrees of freedom. The standard D3Q19 lattice Boltzmann model is derived and explained in depth, followed by a detailed discussion of complementary methods for the coupling of solvent and solute. Colloidal dispersions are best described in terms of extended particles with appropriate boundary conditions at the surfaces, while particles with internal degrees of freedom are easier to simulate as an arrangement of mass points with frictional coupling to the solvent. In both cases, particular care has been taken to simulate thermal fluctuations in a consistent way. The usefulness of this methodology is illustrated by studies from our own research, where the dynamics of colloidal and polymeric systems has been investigated in both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures, 76 page

Assessment of p.Phe508del-CFTR functional restoration in pediatric primary cystic fibrosis airway epithelial cells

© 2018 Sutanto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background Mutations in the cystic fibrosis transmembrane regulator (CFTR) gene can reduce function of the CFTR ion channel activity and impair cellular chloride secretion. The gold standard method to assess CFTR function of ion transport using the Ussing chamber requires a high number of airway epithelial cells grown at air-liquid interface, limiting the application of this method for high throughput screening of potential therapeutic compounds in primary airway epithelial cells (pAECs) featuring less common CFTR mutations. This study assessed an alternative approach, using a small scale halide assay that can be adapted for a personalized high throughput setting to analyze CFTR function of pAEC. Methods Pediatric pAECs derived from children with CF (pAEC CF ) were established and expanded as monolayer cultures, before seeding into 96-well plates for the halide assay. Cells were then transduced with an adenoviral construct containing yellow fluorescent protein (eYFP) reporter gene, alone or in combination with either wild-type CFTR (WT-CFTR) or p.Phe508-del CFTR. Four days post transduction, cells were stimulated with forskolin and genistein, and assessed for quenching of the eYFP signal following injection of iodide solution into the assay media. Results Data showed that pAEC CF can express eYFP at high efficiency following transduction with the eYFP construct. The halide assay was able to discriminate functional restoration of CFTR in pAEC CF treated with either WT-CFTR construct or the positive controls syntaxin 8 and B-cell receptor-associated protein 31 shRNAs. Significance The current study demonstrates that the halide assay can be adapted for pediatric pAEC CF to evaluate restoration of CFTR function. With the ongoing development of small molecules to modulate the folding and/or activity of various mutated CFTR proteins, this halide assay presents a small-scale personalized screening platform that could assess therapeutic potential of molecules across a broad range of CFTR mutations

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Accent, listening assessment and the potential for a shared-L1 advantage:a DIF perspective

This paper reports on an investigation of the potential for a shared-L1 advantage on an academic English listening test featuring speakers with L2 accents. Two hundred and twelve second-language listeners (including 70 Mandarin Chinese L1 listeners and 60 Japanese L1 listeners) completed three versions of the University Test of English as a Second Language (UTESL) listening sub-test which featured an Australian English-accented speaker, a Japanese-accented speaker and a Mandarin Chinese-accented speaker. Differential item functioning (DIF) analyses were conducted on data from the tests which featured L2-accented speakers using two methods of DIF detection – the standardization procedure and the Mantel-Haenszel procedure – with candidates matched for ability on the test featuring the Australian English-accented speaker. Findings showed that Japanese L1 listeners were advantaged on a small number of items on the test featuring the Japanese-accented speaker, but these were balanced by items which favoured non-Japanese L1 listeners. By contrast, Mandarin Chinese L1 listeners were clearly advantaged across several items on the test featuring a Mandarin Chinese L1 speaker. The implications of these findings for claims of bias are discussed with reference to the role of speaker accent in the listening construct