5,436 research outputs found

    Updates in Mechanical Thrombectomy

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    Strokes are a major source of morbidity and mortality worldwide. The long-standing gold standard in stroke therapy, intravenous administration of tissue plasminogen activator (tPA), is limited by strict timing parameters and modest efficacy in large strokes caused by thrombi in the proximal cerebral vasculature. Multiple recent randomized controlled trials have demonstrated the efficacy of mechanical thrombectomy for patients with large vessel occlusions (LVOs). Recent clinical guidelines have been updated to include mechanical thrombectomy as a standard of care in properly selected stroke patients, with ongoing and future studies working to refine the optimal clinical and technical variables of this approach

    Pilot study of a brief provider and EMR-based intervention for overweight teens with asthma

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    INTRODUCTION: Asthma-related morbidity is increased in overweight patients, yet providers are given little guidance on how to discuss weight and asthma management with overweight teens. OBJECTIVE: We piloted an electronic medical record (EMR)-based tailored discussion guide (TDG) and a brief provider training, to address weight management in overweight teens with asthma. The primary outcome was intervention impact on patient-reported asthma outcomes (e.g., asthma control and morbidity). Secondary outcomes included change in BMI, patient-centeredness, and change in healthy behaviors. METHODS: Teens aged 13-18 years with persistent asthma and a body mass index ≄ 85th percentile for their age and sex were eligible. Parents of eligible teens were contacted before an upcoming appointment to allow teen enrollment during the clinic visit. Providers reviewed Motivational Interviewing (MI) concepts and were trained in the TDG for support of conversations around weight and asthma management. Measures included asthma outcomes retrieved from the EMR at 6- and 12-month post-baseline, teen impressions of patient-provider communication at 6-week post-enrollment, and teen report of healthy behaviors at 6- and 12-month post-baseline. RESULTS: Of 44 teens enrolled (77% African-American, 63% female), mean BMI for intervention (n=25) and control groups (n=19) at baseline were similar. Thirty participants (68%) completed a 6-week questionnaire. Compared to controls, at 6 months, intervention teens reported fewer days of limited activity and uncontrolled asthma, but at 12 months, only restricted activity remained lower, and BMI was not reduced. Intervention teens reported clinic visits that were more patient-centered than controls, including discussion of asthma treatment options with provider, feeling ready to follow an asthma treatment routine, and receiving helpful tips about reaching a healthy weight. The healthy behavior dinner with family showed improvement for intervention teens at 6 and 12 months. The feasibility study also revealed a need to improve recruitment strategies and to streamline intervention delivery. CONCLUSION: Modest improvements in patient-reported asthma outcomes and health behaviors were observed. There was strong evidence that the TDG supports provider discussion of weight and asthma to create a more patient-centered conversation from the perspective of participating teens. Challenges to recruitment and clinic adaptation must be addressed before advancing to a full-scale trial. TRIAL REGISTRATION: NCT02575326 Teen Asthma Control Encouraging a Healthier Lifestyle, www.cllinicaltrials.gov

    Neural circuitry governing anxious individuals’ mis-allocation of working memory to threat

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    Dispositional anxiety is a trait-like phenotype that confers increased risk for a range of debilitating neuropsychiatric disorders. Like many patients with anxiety disorders, individuals with elevated levels of dispositional anxiety are prone to intrusive and distressing thoughts in the absence of immediate threat. Recent electrophysiological research suggests that these symptoms are rooted in the misallocation of working memory (WM) resources to threat-related information. Here, functional MRI was used to identify the network of brain regions that support WM for faces and to quantify the allocation of neural resources to threat-related distracters in 81 young adults. Results revealed widespread evidence of mis-allocation. This was evident in both face-selective regions of the fusiform cortex and domain-general regions of the prefrontal and parietal cortices. This bias was exaggerated among individuals with a more anxious disposition. Mediation analyses provided compelling evidence that anxious individuals’ tendency to mis-allocate WM resources to threat-related distracters is statistically explained by heightened amygdala reactivity. Collectively, these results provide a neurocognitive framework for understanding the pathways linking anxious phenotypes to the development of internalizing psychopathology and set the stage for developing improved intervention strategies

    A foundation for provitamin A biofortification of maize: genome-wide association and genomic prediction models of carotenoid levels.

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    Efforts are underway for development of crops with improved levels of provitamin A carotenoids to help combat dietary vitamin A deficiency. As a global staple crop with considerable variation in kernel carotenoid composition, maize (Zea mays L.) could have a widespread impact. We performed a genome-wide association study (GWAS) of quantified seed carotenoids across a panel of maize inbreds ranging from light yellow to dark orange in grain color to identify some of the key genes controlling maize grain carotenoid composition. Significant associations at the genome-wide level were detected within the coding regions of zep1 and lut1, carotenoid biosynthetic genes not previously shown to impact grain carotenoid composition in association studies, as well as within previously associated lcyE and crtRB1 genes. We leveraged existing biochemical and genomic information to identify 58 a priori candidate genes relevant to the biosynthesis and retention of carotenoids in maize to test in a pathway-level analysis. This revealed dxs2 and lut5, genes not previously associated with kernel carotenoids. In genomic prediction models, use of markers that targeted a small set of quantitative trait loci associated with carotenoid levels in prior linkage studies were as effective as genome-wide markers for predicting carotenoid traits. Based on GWAS, pathway-level analysis, and genomic prediction studies, we outline a flexible strategy involving use of a small number of genes that can be selected for rapid conversion of elite white grain germplasm, with minimal amounts of carotenoids, to orange grain versions containing high levels of provitamin A

    Molecular Adhesion between Cartilage Extracellular Matrix Macromolecules

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    In this study, we investigated the molecular adhesion between the major constituents of cartilage extracellular matrix, namely, the highly negatively charged proteoglycan aggrecan and the type II/IX/XI fibrillar collagen network, in simulated physiological conditions. Colloidal force spectroscopy was applied to measure the maximum adhesion force and total adhesion energy between aggrecan end-attached spherical tips (end radius R ≈ 2.5 ÎŒm) and trypsin-treated cartilage disks with undamaged collagen networks. Studies were carried out in various aqueous solutions to reveal the physical factors that govern aggrecan–collagen adhesion. Increasing both ionic strength and [Ca2+] significantly increased adhesion, highlighting the importance of electrostatic repulsion and Ca2+-mediated ion bridging effects. In addition, we probed how partial enzymatic degradation of the collagen network, which simulates osteoarthritic conditions, affects the aggrecan–collagen interactions. Interestingly, we found a significant increase in aggrecan–collagen adhesion even when there were no detectable changes at the macro- or microscales. It is hypothesized that the aggrecan–collagen adhesion, together with aggrecan–aggrecan self-adhesion, works synergistically to determine the local molecular deformability and energy dissipation of the cartilage matrix, in turn, affecting its macroscopic tissue properties.National Science Foundation (U.S.) (Grant CMMI-0758651)National Institutes of Health (U.S.) (Grant AR60331)United States. Dept. of Defense (National Defense Science and Engineering Graduate Fellowship (Grant N00244-09-1-0064))Shriners of North AmericaDrexel University (Faculty Start-up Grant

    Evaluating the diversity and utility of materials proposed by generative models

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    Generative machine learning models can use data generated by scientific modeling to create large quantities of novel material structures. Here, we assess how one state-of-the-art generative model, the physics-guided crystal generation model (PGCGM), can be used as part of the inverse design process. We show that the default PGCGM's input space is not smooth with respect to parameter variation, making material optimization difficult and limited. We also demonstrate that most generated structures are predicted to be thermodynamically unstable by a separate property-prediction model, partially due to out-of-domain data challenges. Our findings suggest how generative models might be improved to enable better inverse design.Comment: 12 pages, 9 figures. Published at SynS & ML @ ICML2023: https://openreview.net/forum?id=2ZYbmYTKo

    The European Forest and Agriculture Optimisation Model -- EUFASOM

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    Land use is a key factor to social wellbeing and has become a major component in political negotiations. This paper describes the mathematical structure of the European Forest and Agricultural Sector Optimization Model. The model represents simultaneously observed resource and technological heterogeneity, global commodity markets, and multiple environmental qualities. Land scarcity and land competition between traditional agriculture, forests, nature reserves, pastures, and bioenergy plantations is explicitly captured. Environmental change, technological progress, and policies can be investigated in parallel. The model is well-suited to estimate competitive economic potentials of land based mitigation, leakage, and synergies and trade-offs between multiple environmental objectives.Land Use Change Optimization, Resource Scarcity, Market Competition, Welfare Maximization, Bottom-up Partial Equilibrium Analysis, Agricultural Externality Mitigation, Forest Dynamics, Global Change Adaptation, Environmental Policy Simulation, Integrated Assessment, Mathematical Programming, GAMS
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