Growth control of oxygen stoichiometry in homoepitaxial SrTiO3 films by pulsed laser epitaxy in high vacuum

In many transition metal oxides (TMOs), oxygen stoichiometry is one of the most critical parameters that plays a key role in determining the structural, physical, optical, and electrochemical properties of the material. However, controlling the growth to obtain high quality single crystal films having the right oxygen stoichiometry, especially in a high vacuum environment, has been viewed as a challenge. In this work, we show that through proper control of the plume kinetic energy, stoichiometric crystalline films can be synthesized without generating oxygen defects, even in high vacuum. We use a model homoepitaxial system of SrTiO3 (STO) thin films on single crystal STO substrates. Physical property measurements indicate that oxygen vacancy generation in high vacuum is strongly influenced by the energetics of the laser plume, and it can be controlled by proper laser beam delivery. Therefore, our finding not only provides essential insight into oxygen stoichiometry control in high vacuum for understanding the fundamental properties of STO-based thin films and heterostructures, but expands the utility of pulsed laser epitaxy of other materials as well

Growth Control of Oxygen Stoichiometry in Homoepitaxial SrTiO\u3csub\u3e3\u3c/sub\u3e Films by Pulsed Laser Epitaxy in High Vacuum

In many transition metal oxides, oxygen stoichiometry is one of the most critical parameters that plays a key role in determining the structural, physical, optical, and electrochemical properties of the material. However, controlling the growth to obtain high quality single crystal films having the right oxygen stoichiometry, especially in a high vacuum environment, has been viewed as a challenge. In this work, we show that, through proper control of the plume kinetic energy, stoichiometric crystalline films can be synthesized without generating oxygen defects even in high vacuum. We use a model homoepitaxial system of SrTiO3 (STO) thin films on single crystal STO substrates. Physical property measurements indicate that oxygen vacancy generation in high vacuum is strongly influenced by the energetics of the laser plume, and it can be controlled by proper laser beam delivery. Therefore, our finding not only provides essential insight into oxygen stoichiometry control in high vacuum for understanding the fundamental properties of STO-based thin films and heterostructures, but expands the utility of pulsed laser epitaxy of other materials as well

Innovative Robot Archetypes for In-Space Construction and Maintenance

The space environment presents unique challenges and opportunities in the assembly, inspection and maintenance of orbital and transit spaceflight systems. While conventional Extra-Vehicular Activity (EVA) technology, out of necessity, addresses each of the challenges, relatively few of the opportunities have been exploited due to crew safety and reliability considerations. Extra-Vehicular Robotics (EVR) is one of the least-explored design spaces but offers many exciting innovations transcending the crane-like Space Shuttle and International Space Station Remote Manipulator System (RMS) robots used for berthing, coarse positioning and stabilization. Microgravity environments can support new robotic archetypes with locomotion and manipulation capabilities analogous to undersea creatures. Such diversification could enable the next generation of space science platforms and vehicles that are too large and fragile to launch and deploy as self-contained payloads. Sinuous manipulators for minimally invasive inspection and repair in confined spaces, soft-stepping climbers with expansive leg reach envelopes and free-flying nanosatellite cameras can access EVA worksites generally not accessible to humans in spacesuits. These and other novel robotic archetypes are presented along with functionality concept

AR2, a novel automatic muscle artifact reduction software method for ictal EEG interpretation: Validation and comparison of performance with commercially available software.

Objective: To develop a novel software method (AR2) for reducing muscle contamination of ictal scalp electroencephalogram (EEG), and validate this method on the basis of its performance in comparison to a commercially available software method (AR1) to accurately depict seizure-onset location. Methods: A blinded investigation used 23 EEG recordings of seizures from 8 patients. Each recording was uninterpretable with digital filtering because of muscle artifact and processed using AR1 and AR2 and reviewed by 26 EEG specialists. EEG readers assessed seizure-onset time, lateralization, and region, and specified confidence for each determination. The two methods were validated on the basis of the number of readers able to render assignments, confidence, the intra-class correlation (ICC), and agreement with other clinical findings. Results: Among the 23 seizures, two-thirds of the readers were able to delineate seizure-onset time in 10 of 23 using AR1, and 15 of 23 using AR2 (

Preconditioning of Cardiosphere-Derived Cells With Hypoxia or Prolyl-4-Hydroxylase Inhibitors Increases Stemness and Decreases Reliance on Oxidative Metabolism

Cardiosphere-derived cells (CDCs), which can be isolated from heart explants, are a promising candidate cell source for infarcted myocardium regeneration. However, current protocols used to expand CDCs require at least 1 month in vitro to obtain sufficient cells for transplantation. We report that CDC culture can be optimized by preconditioning the cells under hypoxia (2% oxygen), which may reflect the physiological oxygen level of the stem cell niche. Under hypoxia, the CDC proliferation rate increased by 1.4-fold, generating 6 × 10(6) CDCs with higher expression of cardiac stem cell and pluripotency gene markers compared to normoxia. Furthermore, telomerase (TERT), cytokines/ligands involved in stem cell trafficking (SDF/CXCR-4), erythropoiesis (EPO), and angiogenesis (VEGF) were increased under hypoxia. Hypoxic preconditioning was mimicked by treatment with two types of hypoxia-inducible factor (HIF) prolyl-4-hydroxylase inhibitors (PHDIs): dimethyloxaloylglycine (DMOG) and 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetic acid (BIC). Despite the difference in specificity, both PHDIs significantly increased c-Kit expression and activated HIF, EPO, and CXCR-4. Furthermore, treatment with PHDIs for 24 h increased cell proliferation. Notably, all hypoxic and PHDI-preconditioned CDCs had decreased oxygen consumption and increased glycolytic metabolism. In conclusion, cells cultured under hypoxia could have potentially enhanced therapeutic potential, which can be mimicked, in part, by PHDIs

Efficacy of Tezepelumab in Patients with Severe, Uncontrolled Asthma Across Multiple Clinically Relevant Subgroups in the NAVIGATOR Study

INTRODUCTION: Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52 weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR. METHODS: NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80 years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Pre-specified and post hoc analyses were performed to evaluate the annualized asthma exacerbation rate (AAER) over 52 weeks in clinically relevant subgroups of patients defined by baseline patient characteristics, medical history, exacerbation triggers, medication eligibility and medication use before and during the study. RESULTS: Tezepelumab reduced the AAER over 52 weeks compared with placebo across a wide range of patient subgroups assessed. Reductions in exacerbations were similar across subgroups defined by baseline patient characteristics, ranging from 48% (95% confidence interval [CI]: 21, 65) to 60% (95% CI: 44, 71) in subgroups analysed by sex, smoking history and body mass index. Among the asthma-related comorbidity subgroups investigated, patients with aspirin or NSAID sensitivity had the greatest reductions in AAER with tezepelumab compared with placebo (83%; 95% CI: 66, 91). In patients eligible to receive dupilumab, tezepelumab reduced exacerbations compared with placebo by 64% (95% CI: 54, 71). Reductions in the AAER with tezepelumab compared with placebo were also observed irrespective of exacerbation trigger category and the number of asthma controller medications patients were receiving at baseline. CONCLUSION: These findings further support the benefits of tezepelumab in patients with severe, uncontrolled asthma and can help to inform healthcare providers\u27 treatment decisions

Modular Robotic Vehicle

A modular robotic vehicle includes a chassis, driver input devices, an energy storage system (ESS), a power electronics module (PEM), modular electronic assemblies (eModules) connected to the ESS via the PEM, one or more master controllers, and various embedded controllers. Each eModule includes a drive wheel containing a propulsion-braking module, and a housing containing propulsion and braking control assemblies with respective embedded propulsion and brake controllers, and a mounting bracket covering a steering control assembly with embedded steering controllers. The master controller, which is in communication with each eModule and with the driver input devices, communicates with and independently controls each eModule, by-wire, via the embedded controllers to establish a desired operating mode. Modes may include a two-wheel, four-wheel, diamond, and omni-directional steering modes as well as a park mode. A bumper may enable docking with another vehicle, with shared control over the eModules of the vehicles

An Expert Consensus Framework for Asthma Remission as a Treatment Goal

With novel therapies in development, there is an opportunity to consider asthma remission as a treatment goal. In this Rostrum, we present a generalized framework for clinical and complete remission in asthma, on and off treatment, developed on the basis of medical literature and expert consensus. A modified Delphi survey approach was used to ascertain expert consensus on core components of asthma remission as a treatment target. Phase 1 identified other chronic inflammatory diseases with remission definitions. Phase 2 evaluated components of those definitions as well as published definitions of spontaneous asthma remission. Phase 3 evaluated a remission framework created using consensus findings. Clinical remission comprised 12 or more months with (1) absence of significant symptoms by validated instrument, (2) lung function optimization/stabilization, (3) patient/provider agreement regarding remission, and (4) no use of systemic corticosteroids. Complete remission was defined as clinical remission plus objective resolution of asthma-related inflammation and, if appropriate, negative bronchial hyperresponsiveness. Remission off treatment required no asthma treatment for 12 or more months. The proposed framework is a first step toward developing asthma remission as a treatment target and should be refined through future research, patient input, and clinical study

Real-World Assessment of Asthma Specialist Visits Among U.S. Patients with Severe Asthma.

BACKGROUND: U.S. guidelines recommend that patients with severe asthma be referred to specialists (allergists/immunologists or pulmonologists) for systematic assessment or comanagement; however, contemporary, real-world data on the frequency and impact of specialist care among U.S. severe asthma patients are lacking. OBJECTIVES: To quantify the frequency of asthma specialist visits among U.S. patients with severe asthma, identify patient demographic and clinical characteristics associated with specialist visits and describe health outcomes following specialist care. METHODS: Severe asthma patients aged 6 years or older were identified between January 1, 2015, and December 31, 2017, in the IQVIA PharMetrics® Plus database of commercially insured individuals, based on Healthcare Effectiveness Data and Information Set (HEDIS) criteria and Global Initiative for Asthma (GINA) step 4 or 5 treatment regimens. The frequency of asthma specialist (allergist/immunologist or pulmonologist) visits was described over 2 years. Patient characteristics associated with having 1 or more specialist visits were analyzed using multivariate regressions. Asthma exacerbations and health care resource utilization before and after specialist visit were compared. RESULTS: Of 54,332 patients identified, 38.2% had 1 or more specialist visits over 2 years. Patient characteristics predictive of specialist visits were asthma exacerbation frequency, younger age, and allergy/respiratory comorbidity burden (all P \u3c .001). Among patients with 1 or more specialist visits, a lower prevalence of asthma exacerbations and rescue inhaler use was observed following the first observed specialist visit. CONCLUSIONS: Specialist care was observed in fewer than half of U.S. patients with severe asthma and was least frequent among older adult patients and those with more nonrespiratory comorbidities. Increased specialist involvement in managing severe asthma may help improve care and patient outcomes