455 research outputs found

    Method of Controlling Steering of a Ground Vehicle

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    A method of controlling steering of a vehicle through setting wheel angles of a plurality of modular electronic corner assemblies (eModules) is provided. The method includes receiving a driving mode selected from a mode selection menu. A position of a steering input device is determined in a master controller. A velocity of the vehicle is determined, in the master controller, when the determined position of the steering input device is near center. A drive mode request corresponding to the selected driving mode to the plurality of steering controllers is transmitted to the master controller. A required steering angle of each of the plurality of eModules is determined, in the master controller, as a function of the determined position of the steering input device, the determined velocity of the vehicle, and the selected first driving mode. The eModules are set to the respective determined steering angles

    Free vibration analysis of laminated composite plates based on FSDT using one-dimensional IRBFN method

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    This paper presents a new effective radial basis function (RBF) collocation technique for the free vibration analysis of laminated composite plates using the first order shear deformation theory (FSDT). The plates, which can be rectangular or non-rectangular, are simply discretised by means of Cartesian grids. Instead of using conventional differentiated RBF networks, one-dimensional integrated RBF networks (1D-IRBFN) are employed on grid lines to approximate the field variables. A number of examples concerning various thickness-to-span ratios, material properties and boundary conditions are considered. Results obtained are compared with the exact solutions and numerical results by other techniques in the literature to investigate the performance of the proposed method

    Altered differentiation of endometrial mesenchymal stromal fibroblasts is associated with endometriosis susceptibility.

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    Cellular development is tightly regulated as mature cells with aberrant functions may initiate pathogenic processes. The endometrium is a highly regenerative tissue, shedding and regenerating each month. Endometrial stromal fibroblasts are regenerated each cycle from mesenchymal stem cells and play a pivotal role in endometriosis, a disease characterised by endometrial cells that grow outside the uterus. Why the cells of some women are more capable of developing into endometriosis lesions is not clear. Using isolated, purified and cultured endometrial cells of mesenchymal origin from 19 women with (n = 10) and without (n = 9) endometriosis we analysed the transcriptome of 33,758 individual cells and compared these to clinical characteristics and in vitro growth profiles. We show purified mesenchymal cell cultures include a mix of mesenchymal stem cells and two endometrial stromal fibroblast subtypes with distinct transcriptomic signatures indicative of varied progression through the differentiation processes. The fibroblast subgroup characterised by incomplete differentiation was predominantly (81%) derived from women with endometriosis and exhibited an altered in vitro growth profile. These results uncover an inherent difference in endometrial cells of women with endometriosis and highlight the relevance of cellular differentiation and its potential to contribute to disease susceptibility

    Concordance of Treatment Effect: An Analysis of The Society of Thoracic Surgeons Intermacs Database

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    BACKGROUND: The Society of Thoracic Surgeons (STS) Intermacs Registry represents a real-world data source of durable, left ventricular assist devices that can address knowledge gaps not informed through randomized clinical trials. We sought to compare survival with contemporary left ventricular assist device technologies using multiple analytic approaches to assess concordance of treatment effects and to validate prior STS Intermacs observations. METHODS: Patients (aged \u3e 19 years) enrolled into STS Intermacs between August 2017 - June 2019 were stratified by device type (centrifugal device with hybrid levitation [CF-HL] or full magnetic levitation [CF-FML]). The primary outcome was 1-year survival assessed by three statistical methodologies (multivariable regression, propensity score matching, and instrumental variable analysis). RESULTS: Of 4,448 patients, 2,012 (45.2%) received CF-HL and 2,436 (54.8%) received CF-FML. One-year survival for CF-FML was 88% vs. 79% for CF-HL (overall p \u3c .001), with a hazard ratio for mortality of 3.18 for CF-HL (p\u3c0.0001) after risk adjustment. With propensity score matching (n=1400 each cohort), 1-year survival was 87% for CF-FML vs. 80% for CF-HL, with a hazard ratio of 3.20 for mortality with CF-HL (p\u3c0.0001) after risk adjustment. With an instrumental variable analysis, the probability of receiving CF-HL was associated with a hazard ratio of 3.11 (p\u3c0.0001). CONCLUSIONS: Statistical methodology using propensity score matching and instrumental variable analysis increased the robustness of observations derived from real-world data and demonstrates the feasibility of performing comparative effectiveness research using STS Intermacs. These analyses provide additional evidence supporting a survival benefit of CF-FML versus CF-HL

    Preventing unauthorized data flows

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    Trojan Horse attacks can lead to unauthorized data flows and can cause either a confidentiality violation or an integrity violation. Existing solutions to address this problem employ analysis techniques that keep track of all subject accesses to objects, and hence can be expensive. In this paper we show that for an unauthorized flow to exist in an access control matrix, a flow of length one must exist. Thus, to eliminate unauthorized flows, it is sufficient to remove all one-step flows, thereby avoiding the need for expensive transitive closure computations. This new insight allows us to develop an efficient methodology to identify and prevent all unauthorized flows leading to confidentiality and integrity violations. We develop separate solutions for two different environments that occur in real life, and experimentally validate the efficiency and restrictiveness of the proposed approaches using real data sets. © IFIP International Federation for Information Processing 2017

    Clinical outcomes and healthcare expenditures in the real world with left ventricular assist devices - The CLEAR-LVAD study

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    BACKGROUND: Several distinctly engineered left ventricular assist devices (LVADs) are in clinical use. However, contemporaneous real world comparisons have not been conducted, and clinical trials were not powered to evaluate differential survival outcomes across devices. OBJECTIVES: Determine real world survival outcomes and healthcare expenditures for commercially available durable LVADs. METHODS: Using a retrospective observational cohort design, Medicare claims files were linked to manufacturer device registration data to identify de-novo, durable LVAD implants performed between January 2014 and December 2018, with follow-up through December 2019. Survival outcomes were compared using a Cox proportional hazards model stratified by LVAD type and validated using propensity score matching. Healthcare resource utilization was analyzed across device types by using nonparametric bootstrap analysis methodology. Primary outcome was survival at 1-year and total Part A Medicare payments. RESULTS: A total of 4,195 de-novo LVAD implants were identified in fee-for-service Medicare beneficiaries (821 HeartMate 3; 1,840 HeartMate II; and 1,534 Other-VADs). The adjusted hazard ratio for mortality at 1-year (confirmed in a propensity score matched analysis) for the HeartMate 3 vs HeartMate II was 0.64 (95% CI; 0.52-0.79, p\u3c 0.001) and for the HeartMate 3 vs Other-VADs was 0.51 (95% CI; 0.42-0.63, p \u3c 0.001). The HeartMate 3 cohort experienced fewer hospitalizations per patient-year vs Other-VADs (respectively, 2.8 vs 3.2 EPPY hospitalizations, p \u3c 0.01) and 6.1 fewer hospital days on average (respectively, 25.2 vs 31.3 days, p \u3c 0.01). The difference in Medicare expenditures, conditional on survival, for HeartMate 3 vs HeartMate II was -10,722,p3˘c0.001(17.410,722, p \u3c 0.001 (17.4% reduction) and for HeartMate 3 vs Other-VADs was -17,947, p \u3c 0.001 (26.1% reduction). CONCLUSIONS: In this analysis of a large, real world, United States. administrative dataset of durable LVADs, we observed that the HeartMate 3 had superior survival, reduced healthcare resource use, and lower healthcare expenditure compared to other contemporary commercially available LVADs

    Computational Protein Design to Re-Engineer Stromal Cell-Derived Factor-1α (SDF) Generates an Effective and Translatable Angiogenic Polypeptide Analog

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    BACKGROUND: Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein. METHODS AND RESULTS: Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls. CONCLUSIONS: Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy

    A Mathematical model for Astrocytes mediated LTP at Single Hippocampal Synapses

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    Many contemporary studies have shown that astrocytes play a significant role in modulating both short and long form of synaptic plasticity. There are very few experimental models which elucidate the role of astrocyte over Long-term Potentiation (LTP). Recently, Perea & Araque (2007) demonstrated a role of astrocytes in induction of LTP at single hippocampal synapses. They suggested a purely pre-synaptic basis for induction of this N-methyl-D- Aspartate (NMDA) Receptor-independent LTP. Also, the mechanisms underlying this pre-synaptic induction were not investigated. Here, in this article, we propose a mathematical model for astrocyte modulated LTP which successfully emulates the experimental findings of Perea & Araque (2007). Our study suggests the role of retrograde messengers, possibly Nitric Oxide (NO), for this pre-synaptically modulated LTP.Comment: 51 pages, 15 figures, Journal of Computational Neuroscience (to appear

    HVAD to HeartMate 3 left ventricular assist device exchange: Best practices recommendations

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    The HeartWare HVAD System (Medtronic) is a durable implantable left ventricular assist device that has been implanted in approximately 20,000 patients worldwide for bridge to transplant and destination therapy indications. In December 2020, Medtronic issued an Urgent Medical Device Communication informing clinicians of a critical device malfunction in which the HVAD may experience a delay or failure to restart after elective or accidental discontinuation of pump operation. Moreover, evolving retrospective comparative effectiveness studies of patients supported with the HVAD demonstrated a significantly higher risk of stroke and all-cause mortality when compared with a newer generation of a commercially available durable left ventricular assist device. Considering the totality of this new information on HVAD performance and the availability of an alternate commercially available device, Medtronic halted the sale and distribution of the HVAD System in June 2021. The decision to remove the HVAD from commercial distribution now requires the use of the HeartMate 3 left ventricular assist system (Abbott, Inc) if a patient previously implanted with an HVAD requires a pump exchange. The goal of this document is to review important differences in the design of the HVAD and HeartMate 3 that are relevant to the medical management of patients supported with these devices, and to assess the technical aspects of an HVAD-to-HeartMate 3 exchange. This document provides the best available evidence that supports best practices
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