2,801 research outputs found

    Novel therapeutic approaches to familial HLH (emapalumab in FHL)

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    Primary Hemophagocytic lymphohistiocytosis (pHLH) is a rare, life-threatening, hyperinflammatory disorder, characterized by uncontrolled activation of the immune system. Mutations affecting several genes coding for proteins involved in the cytotoxicity machinery of both natural killer (NK) and T cells have been found to be responsible for the development of pHLH. So far, front-line treatment, established on the results of large international trials, is based on the use of glucocorticoids, etoposide ± cyclosporine, followed by allogeneic hematopoietic stem cell transplantation (HSCT), the sole curative treatment for the genetic forms of the disease. However, despite major efforts to improve the outcome of pHLH, many patients still experience unfavorable outcomes, as well as severe toxicities; moreover, treatment-refractory or relapsing disease is a major challenge for pediatricians/hematologists. In this article, we review the epidemiology, etiology and pathophysiology of pHLH, with a particular focus on different cytokines at the origin of the disease. The central role of interferon-γ (IFNγ) in the development and maintenance of hyperinflammation is analyzed. The value of emapalumab, a novel IFNγ-neutralizing monoclonal antibody is discussed. Available data support the use of emapalumab for treatment of pHLH patients with refractory, recurrent or progressive disease, or intolerance to conventional therapy, recently, leading to FDA approval of the drug for these indications. Additional data are needed to define the role of emapalumab in front-line treatment or in combination with other drugs

    Microfoundations Approach to Risk and Uncertainty in the Uppsala Internationalization Process

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    This study answers rising calls in International Business to employ a microfoundations approach for greater insight on differences in managerial cognition for entering business in high-risk locations. Consequently, findings challenge the Uppsala model’s longstanding stance concerning the risk-internationalization association governed by strict firm-level analysis. I examine CEO decision-making through the lens of their values, represented by their political ideology score along the liberal-conservative continuum, to offer greater predictability for rationalizing strategic choices. Accordingly, political ideology proved a significant predictor for explaining the circumstances in which CEOs elect high-risk locations based on their political ideology’s degree of liberalism. Additionally, its interactions with prominent predictors, such as managerial discretion and compensation incentives, underscore how these influences are perceived differently between liberals and conservatives’ perception of risk

    How good are we at determining risk? Quantifying the accuracy of clinician determined risk for VTE prophylaxis

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    Objectives: Create and validate a simple tool for concurrent audits of risk stratification, compliance and documentation Evaluate accuracy of clinician risk stratification and prophylatic ordering practice compared with a standardized Caprini RAM across different assigned risk categories Provide recommendations for EPIC VTE Prophylaxis CDS Developmenthttps://jdc.jefferson.edu/patientsafetyposters/1050/thumbnail.jp

    Cathode Active Material Recycling from Spent Lithium Batteries: A Green (Circular) Approach Based on Deep Eutectic Solvents

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    The transition to a circular economy vision must handle the increasing request of metals required to satisfy the battery industry; this can be obtained by recycling and feeding back secondary raw materials recovered through proper waste management. Here, a novel and green proof-of-concept was developed, based on deep eutectic solvents (DESs) to fully and easily recover valuable metals from various cathode active materials, including LiMn2O4, LiNi0.5Mn1.5O4, and LiNi0.8Co0.2O2. DES composed of choline chloride and lactic acid could leach Li, Mn, Co, and Ni, achieving efficiency of 100 % under much milder conditions with respect to the previous literature. For the first time, to our best knowledge, a two-step approach was reported in the case of LiNi0.8Co0.2O2 for selective recovery of Li, Co, and Ni with high yield and purity. Furthermore, other cathode components, namely aluminum current collector and binder, were found to be not dissolved by the proposed DES, thus making a simple separation from the active material possible. Finally, this strategy was designed to easily regenerate and reuse the leaching solvents for more than one extraction, thus further boosting process sustainability

    Quantifying Patient Reported and Documented Compliance with Adjuncts to Venous Thromboembolism Prophylaxis

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    Objectives: 1. Measure patient compliance with pharmacologic, mechanical and ambulatory prophylactic measures. 2. Evaluate for agreement between nursing documentation and patient reported compliance with mechanical and ambulatory prophylactic measures.https://jdc.jefferson.edu/patientsafetyposters/1042/thumbnail.jp

    Research Note: Bayesian Record Linkage with Application to Chinese Immigrants in Raleigh-Durham (ChIRDU) Study

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    Many population surveys do not provide information on respondents' residential addresses, instead offering coarse geographies like zip code or higher aggregations. However, fine resolution geography can be beneficial for characterizing neighborhoods, especially for relatively rare populations such as immigrants. One way to obtain such information is to link survey records to records in auxiliary databases that include residential addresses by matching on variables common to both files. In this research note, we present an approach based on probabilistic record linkage that enables matching survey participants in the Chinese Immigrants in Raleigh-Durham (ChIRDU) Study to records from InfoUSA, an information provider of residential records. The two files use different Chinese name romanization practices, which we address through a novel and generalizable strategy for constructing records' pairwise comparison vectors for romanized names. Using a fully Bayesian record linkage model, we characterize the geospatial distribution of Chinese immigrants in the Raleigh-Durham area

    Dopant profiling on ultra shallow junctions in Si with ADF-STEM

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    The utmost scaling of the electronic devices nowadays attained, requires both ultra shallow junctions and high levels of dopant concentration and activation. In these conditions, the presence of surfaces or interfaces assumes a very important role in the determination of the dopant distribution during post-implantation annealing. In this work, we show how the Z-contrast annular dark field scanning transmission electron microscopy (ADF-STEM) technique, pionereed by Pennycook and coworkers [1], can be optimised to give reliable dopant profiles at a subnanometer scale thus satisfying some of the new needs of the ultra shallow implants characterization
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