Using Nanoparticle X-ray Spectroscopy to Probe the Formation of Reactive Chemical Gradients in Diffusion-Limited Aerosols.

For aerosol particles that exist in highly viscous, diffusion-limited states, steep chemical gradients are expected to form during photochemical aging in the atmosphere. Under these conditions, species at the aerosol surface are more rapidly transformed than molecules residing in the particle interior. To examine the formation and evolution of chemical gradients at aerosol interfaces, the heterogeneous reaction of hydroxyl radicals (OH) on ∼200 nm particles of pure squalane (a branched, liquid hydrocarbon) and octacosane (a linear, solid hydrocarbon) and binary mixtures of the two are used to understand how diffusion limitations and phase separation impact the particle reactivity. Aerosol mass spectrometry is used to measure the effective heterogeneous OH uptake coefficient (γeff) and oxidation kinetics in the bulk, which are compared with the elemental composition of the surface obtained using X-ray photoemission. When diffusion rates are fast relative to the reaction frequency, as is the case for squalane and low-viscosity squalane-octacosane mixtures, the reaction is efficient (γeff ∼ 0.3) and only limited by the arrival of OH to the interface. However, for cases, where the diffusion rates are slower than reaction rates, as in pure octacosane and higher-viscosity squalane-octacosane mixtures, the heterogeneous reaction occurs in a mixing-limited regime and is ∼10× slower (γeff ∼ 0.03). This is in contrast to carbon and oxygen K edge X-ray absorption measurements that show that the octacosane interface is oxidized much more rapidly than that of pure squalane particles. The O/C ratio of the surface (estimated to be the top 6-8 nm of the interface) is measured to change with rate constants of (3.0 ± 0.9) × 10-13 and (8.6 ± 1.2) × 10-13 cm3 molecule-1 s-1 for squalane and octacosane particles, respectively. The differences in surface oxidation rates are analyzed using a previously published reaction-diffusion model, which suggests that a 1-2 nm highly oxidized crust forms on octacosane particles, whereas in pure squalane, the reaction products are homogeneously mixed within the aerosol. This work illustrates how diffusion limitations can form particles with highly oxidized surfaces even at relatively low oxidant exposures, which is in turn expected to influence their microphysics in the atmosphere

Modeling and analysis of uncertain time-critical tasking problems

Naval Research Logistics, 53 , No. 6, (Sept. 2006), 588-599.This paper describes modeling and operational analysis of a generic asymmetric services-system situation in which (a) Red agents, potentially threatening, but in another but important interpretation, are isolated friendlies, such as downed pilots, that require assistance and "arrive" according to some partially known and potentially changing pattern in time and space: and (b) Reds have effectively limited unknown deadlines or times of availability for Blue service, i.e., detection, classification, and attack in a military setting or emergency assistance in others. We discuss various service options by Blue service agents and devise several approximations allowing one to compute efficiently those proportions of tasks of different classes that are successfully serviced, or more generally, if different rewards are associated with different classes of tasks, the percentage of the possible reward gained. We suggest heuristic policies of a Blue server to select the next task to perform and to decide how much time to allocate to that service. We discuss this for a number of specific examples

Effect of fixed-dose subcutaneous reslizumab on asthma exacerbations in patients with severe uncontrolled asthma and corticosteroid sparing in patients with oral corticosteroid-dependent asthma : results from two phase 3, randomised, double-blind, placebo-controlled trials

BACKGROUND: Reslizumab 3 mg/kg administered intravenously is approved for the treatment of severe eosinophilic asthma. We assessed the safety and efficacy of subcutaneous reslizumab 110 mg in two trials in patients with uncontrolled severe asthma and increased blood eosinophils. The aim was to establish whether subcutaneous reslizumab 110 mg can reduce exacerbation rates in these patients (study 1) or reduce maintenance oral corticosteroid dose in patients with corticosteroid-dependent asthma (study 2). METHODS: Both studies were randomised, double-blind, placebo-controlled, phase 3 studies. Entry criteria for study 1 were uncontrolled severe asthma, two or more asthma exacerbations in the previous year, a blood eosinophil count of 300 cells per μL or more (including no more than 30% patients with an eosinophil count <400 cells/μL), and at least a medium dose of inhaled corticosteroids with one or more additional asthma controllers. Patients in study 2 had severe asthma, a blood eosinophil count of 300 cells per μL or more, daily maintenance oral corticosteroid (prednisone 5-40 mg, or equivalent), and high-dose inhaled corticosteroids plus another controller. Patients were randomly assigned (1:1) to subcutaneous reslizumab (110 mg) or placebo once every 4 weeks for 52 weeks in study 1 and 24 weeks in study 2. Patients and investigators were masked to treatment assignment. Primary efficacy outcomes were frequency of exacerbations during 52 weeks in study 1 and categorised percentage reduction in daily oral corticosteroid dose from baseline to weeks 20-24 in study 2. Primary efficacy analyses were by intention to treat, and safety analyses included all patients who received at least one dose of study treatment. These studies are registered with ClinicalTrials.gov, NCT02452190 (study 1) and NCT02501629 (study 2). FINDINGS: Between Aug 12, 2015, and Jan 31, 2018, 468 patients in study 1 were randomly assigned to placebo (n=232) or subcutaneous reslizumab (n=236), and 177 in study 2 to placebo (n=89) or subcutaneous reslizumab (n=88). In study 1, we found no significant difference in the exacerbation rate between reslizumab and placebo in the intention-to-treat population (rate ratio 0·79, 95% CI 0·56-1·12; p=0·19). Subcutaneous reslizumab reduced exacerbation frequency compared with placebo in the subgroup of patients with blood eosinophil counts of 400 cells per μL or more (0·64, 95% CI 0·43-0·95). Greater reductions in annual exacerbation risk (p=0·0035) and longer time to first exacerbation were observed for patients with higher trough serum reslizumab concentrations. In study 2, we found no difference between placebo and fixed-dose subcutaneous reslizumab in categorised percentage reduction in daily oral corticosteroid dose (odds ratio for a lower category of oral corticosteroid use in the reslizumab group vs the placebo group, 1·23, 95% CI 0·70-2·16; p=0·47). The frequency of adverse events and serious adverse events with reslizumab were similar to those with placebo in both studies. INTERPRETATION: Fixed-dose (110 mg) subcutaneous reslizumab was not effective in reducing exacerbation frequency in patients with uncontrolled asthma and increased blood eosinophils (≥300 cells/μL), or in reducing the daily maintenance oral corticosteroid dose in patients with oral corticosteroid-dependent severe eosinophilic asthma. Higher exposures than those observed with 110 mg subcutaneous reslizumab are required to achieve maximal efficacy. FUNDING: Teva Branded Pharmaceutical Products R&D

Physiological responses to moderate intensity continuous and high-intensity interval exercise in persons with paraplegia

Randomized crossover. To test differences in the duration and magnitude of physiological response to isocaloric moderate intensity continuous (MICE) and high-intensity interval exercise (HIIE) sessions in persons with spinal cord injury (SCI). Academic medical center in Miami, FL, USA. Ten adult men (mean ± s.d.; 39 ± 10 year old) with chronic (13.2 ± 8.8 year) paraplegia (T2-T10) completed a graded exercise test. Then, in a randomized order, participants completed MICE and HIIE for a cost of 120 kcal. MICE was performed at 24.6% PO . During HIIE, exercise was completed in 2 min work and recovery phases at 70%:10% PO . MICE and HIIE were isocaloric (115.9 ± 21.8 and 116.6 ± 35.0 kcal, respectively; p = 0.903), but differed in duration (39.8 ± 4.6 vs 32.2 ± 6.2 min; p < 0.001) and average respiratory exchange ratio (RER; 0.90 ± 0.08 vs 1.01 ± 0.07; p = 0.002). During MICE, a workrate of 24.6 ± 6.7% PO elicited a V̇O of 53.1 ± 6.5% V̇O (10.1 ± 2.2 ml kg  min ). During HIIE, a workrate at 70% PO elicited 88.3 ± 6.7% V̇O (16.9 ± 4.2 ml kg  min ), and 29.4 ± 7.7% of the session was spent at or above 80% V̇O . During HIIE working phase, RER declined from the first to last interval (1.08 ± 0.07 vs 0.98 ± 0.09; p < 0.001), reflecting an initially high but declining glycolytic rate. Compared with MICE, HIIE imposed a greater physiological stimulus while requiring less time to achieve a target caloric expenditure. Thus, exercise intensity might be an important consideration in the tailoring of exercise prescription to address the cardiometabolic comorbidities of SCI

Physiological responses to moderate intensity continuous and high-intensity interval exercise in persons with paraplegia

Study design: Randomized crossover. Objectives: To test differences in the duration and magnitude of physiological response to isocaloric moderate intensity continuous (MICE) and high-intensity interval exercise (HIIE) sessions in persons with spinal cord injury (SCI). Setting: Academic medical center in Miami, FL, USA. Methods: Ten adult men (mean ± s.d.; 39 ± 10 year old) with chronic (13.2 ± 8.8 year) paraplegia (T2–T10) completed a graded exercise test. Then, in a randomized order, participants completed MICE and HIIE for a cost of 120 kcal. MICE was performed at 24.6% PO peak. During HIIE, exercise was completed in 2 min work and recovery phases at 70%:10% PO peak. Results: MICE and HIIE were isocaloric (115.9 ± 21.8 and 116.6 ± 35.0 kcal, respectively; p = 0.903), but differed in duration (39.8 ± 4.6 vs 32.2 ± 6.2 min; p &lt; 0.001) and average respiratory exchange ratio (RER; 0.90 ± 0.08 vs 1.01 ± 0.07; p = 0.002). During MICE, a workrate of 24.6 ± 6.7% PO peak elicited a V̇O 2 of 53.1 ± 6.5% V̇O 2peak (10.1 ± 2.2 ml kg −1 min −1). During HIIE, a workrate at 70% PO peak elicited 88.3 ± 6.7% V̇O 2peak (16.9 ± 4.2 ml kg −1 min −1), and 29.4 ± 7.7% of the session was spent at or above 80% V̇O 2peak. During HIIE working phase, RER declined from the first to last interval (1.08 ± 0.07 vs 0.98 ± 0.09; p &lt; 0.001), reflecting an initially high but declining glycolytic rate. Conclusions: Compared with MICE, HIIE imposed a greater physiological stimulus while requiring less time to achieve a target caloric expenditure. Thus, exercise intensity might be an important consideration in the tailoring of exercise prescription to address the cardiometabolic comorbidities of SCI. </p

Effects of exercise mode on postprandial metabolism in humans with chronic paraplegia:Exercise and postprandial metabolism in SCI

PURPOSE: The purpose of this study was to assess the acute effects of exercise mode and intensity on postprandial macronutrient metabolism.METHODS: Ten healthy men age 39 ± 10 yr with chronic paraplegia (13.2 ± 8.8 yr, ASIA A-C) completed three isocaloric bouts of upper-body exercise and a resting control. After an overnight fast, participants completed circuit resistance exercise (CRE) first and the following conditions in a randomized order, separated by >48 h: i) control (CON), ~45-min seated rest; ii) moderate-intensity continuous exercise (MICE), ~40-min arm cranking at a resistance equivalent to ~30% peak power output (PPO); and iii) high-intensity interval exercise (HIIE), ~30 min arm cranking with resistance alternating every 2 min between 10% PPO and 70% PPO. After each condition, participants completed a mixed-meal tolerance test consisting of a 2510-kJ liquid meal (35% fat, 50% carbohydrate, 15% protein). Blood and expired gas samples were collected at baseline and regular intervals for 150 min after a meal.RESULTS: An interaction (P < 0.001) was observed, with rates of lipid oxidation elevated above CON in HIIE until 60 min after a meal and in CRE at all postprandial time points up to 150 min after a meal. Postprandial blood glycerol was greater in MICE (P = 0.020) and CRE (P = 0.001) compared with CON. Furthermore, nonesterified fatty acid area under the curve had a moderate-to-strong effect in CRE versus MICE and HIIE (Cohen's d = -0.76 and -0.50, respectively).CONCLUSIONS: In persons with paraplegia, high-intensity exercise increased postprandial energy expenditure independent of the energy cost of exercise. Furthermore, exercise combining resistance and endurance modes (CRE) showed the greater effect on postprandial lipid oxidation

Effects of exercise mode on postprandial metabolism in humans with chronic paraplegia:Exercise and postprandial metabolism in SCI

PURPOSE: The purpose of this study was to assess the acute effects of exercise mode and intensity on postprandial macronutrient metabolism.METHODS: Ten healthy men age 39 ± 10 yr with chronic paraplegia (13.2 ± 8.8 yr, ASIA A-C) completed three isocaloric bouts of upper-body exercise and a resting control. After an overnight fast, participants completed circuit resistance exercise (CRE) first and the following conditions in a randomized order, separated by &gt;48 h: i) control (CON), ~45-min seated rest; ii) moderate-intensity continuous exercise (MICE), ~40-min arm cranking at a resistance equivalent to ~30% peak power output (PPO); and iii) high-intensity interval exercise (HIIE), ~30 min arm cranking with resistance alternating every 2 min between 10% PPO and 70% PPO. After each condition, participants completed a mixed-meal tolerance test consisting of a 2510-kJ liquid meal (35% fat, 50% carbohydrate, 15% protein). Blood and expired gas samples were collected at baseline and regular intervals for 150 min after a meal.RESULTS: An interaction (P &lt; 0.001) was observed, with rates of lipid oxidation elevated above CON in HIIE until 60 min after a meal and in CRE at all postprandial time points up to 150 min after a meal. Postprandial blood glycerol was greater in MICE (P = 0.020) and CRE (P = 0.001) compared with CON. Furthermore, nonesterified fatty acid area under the curve had a moderate-to-strong effect in CRE versus MICE and HIIE (Cohen's d = -0.76 and -0.50, respectively).CONCLUSIONS: In persons with paraplegia, high-intensity exercise increased postprandial energy expenditure independent of the energy cost of exercise. Furthermore, exercise combining resistance and endurance modes (CRE) showed the greater effect on postprandial lipid oxidation.</p

The Variable Vector Countermeasure Suit (V2Suit) for space habitation and exploration

The “Variable Vector Countermeasure Suit (V2Suit) for Space Habitation and Exploration” is a novel system concept that provides a platform for integrating sensors and actuators with daily astronaut intravehicular activities to improve health and performance, while reducing the mass and volume of the physiologic adaptation countermeasure systems, as well as the required exercise time during long-duration space exploration missions. The V2Suit system leverages wearable kinematic monitoring technology and uses inertial measurement units (IMUs) and control moment gyroscopes (CMGs) within miniaturized modules placed on body segments to provide a “viscous resistance” during movements against a specified direction of “down”—initially as a countermeasure to the sensorimotor adaptation performance decrements that manifest themselves while living and working in microgravity and during gravitational transitions during long-duration spaceflight, including post-flight recovery and rehabilitation. Several aspects of the V2Suit system concept were explored and simulated prior to developing a brassboard prototype for technology demonstration. This included a system architecture for identifying the key components and their interconnects, initial identification of key human-system integration challenges, development of a simulation architecture for CMG selection and parameter sizing, and the detailed mechanical design and fabrication of a module. The brassboard prototype demonstrates closed-loop control from “down” initialization through CMG actuation, and provides a research platform for human performance evaluations to mitigate sensorimotor adaptation, as well as a tool for determining the performance requirements when used as a musculoskeletal deconditioning countermeasure. This type of countermeasure system also has Earth benefits, particularly in gait or movement stabilization and rehabilitation.United States. National Aeronautics and Space Administration (Innovative Advanced Concepts Grant NNX11AR25G)United States. National Aeronautics and Space Administration (Innovative Advanced Concepts Grant NNX12AQ58G

A Continuum of Testing (presentation)

Prepared for the National Test & Evaluation Conference, March 200

Hostility Modifies the Association between TV Viewing and Cardiometabolic Risk

Background. It was hypothesized that television viewing is predictive of cardiometabolic risk. Moreover, people with hostile personality type may be more susceptible to TV-induced negative emotions and harmful health habits which increase occurrence of cardiometabolic risk. Purpose. The prospective association of TV viewing on cardiometabolic risk was examined along with whether hostile personality trait was a modifier. Methods. A total of 3,269 Black and White participants in the coronary artery risk development in young adults (CARDIA) study were assessed from age 23 to age 35. A cross-lagged panel model at exam years 5, 10, 15, and 20, covering 15 years, was used to test whether hours of daily TV viewing predicted cardiometabolic risk, controlling confounding variables. Multiple group analysis of additional cross-lagged panel models stratified by high and low levels of hostility was used to evaluate whether the association was modified by the hostile personality trait. Results. The cross-lagged association of TV viewing at years 5 and 15 on clustered cardiometabolic risk score at years 10 and 20 was significant (B=0.058 and 0.051), but not at 10 to 15 years. This association was significant for those with high hostility (B=0.068 for exam years 5 to 10 and 0.057 for exam years 15 to 20) but not low hostility. Conclusion. These findings indicate that TV viewing is positively associated with cardiometabolic risk. Further, they indicate that hostility might be a modifier for the association between TV viewing and cardiometabolic risk