16 research outputs found

    Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study)

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    Background Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19.Methods In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76).Findings Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81-94] in arm A vs 85% [74-93], HR 1.07 [0.8-1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77-96] vs 79% [63-91], HR 1.55 [0.9-2.6]; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7]; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths.Interpretation The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results.Funding This study was supported by INMI "Lazzaro Spallanzani" Ricerca Corrente Linea 1 on emerging and ree-merging infections, funded by Italian Ministry of Health.Copyright (c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

    Synergy between vitamin D and sex hormones in respiratory functionality of patients affected by COVID-19

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    The outcome of COVID-19 appears to be influenced by vitamin D status of population. Although epidemiological data indicate that COVID-19 produces more severe symptoms and higher mortality in elderly in comparison to young patients and in men in comparison to women to date sex and age differences in vitamin D status in infected patients have not been evaluated yet. In this study we evaluated the levels of circulating 25(OH)D in patients hospitalized for COVID-19 divided accordingly to their sex and age. We also correlated 25(OH)D levels with patient’s respiratory status (i.e., PaO2/FiO2 ratio) and with sex hormones plasma levels to analyze the potential relationship of these parameters. We found no significant differences in plasma levels of 25(OH)D between pre- and post-menopausal female patients and age matched male patients. Interestingly, the 25(OH)D plasma levels positively correlated to PaO2/FiO2 ratio only in young patients, regardless of their sex. We also found a significantly positive correlation between 17β-estradiol and 25(OH)D in elderly women and between testosterone and 25(OH)D in elderly men, supporting the role of sex hormones in maintaining 25(OH)D levels. In conclusion, we suggest that a synergy between vitamin D and sex hormones could contribute to the age-related outcome of COVID-19

    Switching Dynamics of Ag-Based Filamentary Volatile Resistive Switching Devices--Part II: Mechanism and Modeling

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    Understanding the switching mechanism of the volatile resistive switching random access memory (RRAM) device is important to harness its characteristics and further enhance its performance. Accurate modeling of its dynamic behavior is also of deep value for its applications both as selector and as short-term memory synapse for future neuromorphic applications operating in temporal domain. In this work, we investigate the switching and retention (relaxation) processes of the Ag-based metallic filamentary volatile resistive switching devices. We find that the switching process can be modeled by the ionic drift under electric field, while the retention process can be modeled by the ionic diffusion along the filament surface driven by the gradient of surface atomic concentration. Through further theoretical analysis, we also find that the ionic drift and ionic diffusion can be unified within the general Einstein relation. To confirm this relation, we collect ionic mobility and diffusivity data from the literature using the switching and retention model. Finally, we show that the read voltage dependent retention time can be explained by the competition between the ionic drift and diffusion flux

    Thermal switching of TiO2-based RRAM for parameter extraction and neuromorphic engineering

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    Recently, resistive switching random access memory (RRAM) has gained maturity for storage class memory and inmemory computing. For these applications, an improved control of the switching phenomena can lead to higher data density and computing accuracy, thus paving the way for RRAM-based artificial intelligence (AI) accelerators for edge computing. This work presents a study of thermally-induced switching in TiO2-based RRAM devices. Thermal switching is explained by defect rediffusion controlled by the activation energy for defect migration in TiO2 . Experiments and simulations support thermal switching as a tool for parameter extraction in RRAM, as well as for novel neuromorphic cognitive functions for brain-inspired computing

    Raphael Painter and Architect in Rome

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    In occasione del cinquecentenario della morte di Raffaello Sanzio (1483-1520) si propone un testo agile e informato per scoprire dipinti e architetture eseguiti a Roma dall\u2019arrivo nell\u2019Urbe nel 1508 alla morte nel 1520. Aggiornate e complete dei dati essenziali, le schede esplicative illustrano l\u2019ampio ventaglio della produzione matura del Raffaello pittore, dagli affreschi alle pale d\u2019altare ai ritratti eseguiti per Roma o oggi l\uec conservati, e permettono di individuare e di comprendere le tracce dell\u2019attivit\ue0 del Raffaello architetto. Si svolge attraverso le opere il racconto dell\u2019appassionante stagione romana dell\u2019artista, impegnato nel continuo rinnovamento del proprio linguaggio di pittore nel dialogo travolgente con Michelangelo, nella gara con Sebastiano del Piombo, nella spinta possente delle sollecitazioni fornite dal repertorio antico della scultura, nel nuovo impegno come caposcuola, alla guida di una bottega che far\ue0 da modello per tutto il secolo e oltre, e si segue il definirsi proprio a Roma dei suoi interessi di architetto e degli obiettivi che egli matura sul fronte dell\u2019architettura moderna su sollecitazione di Bramante e poi di altri, nella sfida costituita dal confronto con i resti degli edifici antichi, in uno scambio costante con gli umanisti, come Pietro Bembo e Fra Giocondo, suoi ferventi interlocutori, committenti, sostenitori. Il testo non trascura di segnalare le opere non accessibili legate all\u2019operato del Sanzio, quali, in Vaticano, le Logge o l\u2019Appartamento del cardinal Bibbiena, o quelle che da architetto egli non pot\ue9 realizzare ma di cui ci restano suoi progetti, o che vennero distrutte (Palazzo Branconio dell\u2019Aquila), e dedica un\u2019attenzione speciale, per la forza del suo rapporto con il presente, alla lettera a Leone X scritta da Raffaello e da Baldassarre Castiglione, riconosciuta come primo documento di una consapevole riflessione sull\u2019urgenza della conservazione dell\u2019architettura e dell\u2019arte del passato alla quale oggi pi\uf9 di allora siamo chiamati a rispondere

    Alouatta caraya:

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    Raffaello pittore e architetto a Roma

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    In occasione del cinquecentenario della morte di Raffaello Sanzio (1483-1520) si propone un testo agile e informato per scoprire dipinti e architetture eseguiti a Roma dall’arrivo nell’Urbe nel 1508 alla morte nel 1520. Aggiornate e complete dei dati essenziali, le schede esplicative illustrano l’ampio ventaglio della produzione matura del Raffaello pittore, dagli affreschi alle pale d’altare ai ritratti eseguiti per Roma o oggi lì conservati, e permettono di individuare e di comprendere le tracce dell’attività del Raffaello architetto. Si svolge attraverso le opere il racconto dell’appassionante stagione romana dell’artista, impegnato nel continuo rinnovamento del proprio linguaggio di pittore nel dialogo travolgente con Michelangelo, nella gara con Sebastiano del Piombo, nella spinta possente delle sollecitazioni fornite dal repertorio antico della scultura, nel nuovo impegno come caposcuola, alla guida di una bottega che farà da modello per tutto il secolo e oltre, e si segue il definirsi proprio a Roma dei suoi interessi di architetto e degli obiettivi che egli matura sul fronte dell’architettura moderna su sollecitazione di Bramante e poi di altri, nella sfida costituita dal confronto con i resti degli edifici antichi, in uno scambio costante con gli umanisti, come Pietro Bembo e Fra Giocondo, suoi ferventi interlocutori, committenti, sostenitori. Il testo non trascura di segnalare le opere non accessibili legate all’operato del Sanzio, quali, in Vaticano, le Logge o l’Appartamento del cardinal Bibbiena, o quelle che da architetto egli non poté realizzare ma di cui ci restano suoi progetti, o che vennero distrutte (Palazzo Branconio dell’Aquila), e dedica un’attenzione speciale, per la forza del suo rapporto con il presente, alla lettera a Leone X scritta da Raffaello e da Baldassarre Castiglione, riconosciuta come primo documento di una consapevole riflessione sull’urgenza della conservazione dell’architettura e dell’arte del passato alla quale oggi più di allora siamo chiamati a rispondere

    A systematic review aimed at studying the influence of educational attainment of HAART compliance

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    Background The introduction of Highly Active Antiretroviral Therapy (HAART) has definitely improved the quality of HIV patients’ life, although its benefits depend on a strict compliance to therapy. Compliance can be considered as a dynamic process influenced by several variables that include some modifiable determinants such as education. The knowledge of its influence on compliance can lead to change the approach to the HIV patients. The aim of this study is to understand if educational attainment conditions HAART compliance. Methods The present search represents an update of a previous review on the same topic. Studies were selected using Boolean strings in PubMed and Scopus as databases. A snowball analysis was executed too in order to widen the number of articles. Inclusion criteria were: post-HAART era (1996), concerning adult patients ( 18 years), written in English. A data abstraction form was used to abstract and to record study details by two researchers. Methodological quality of studies was furtherly evaluated through Newcastle-Ottawa Scale (NOS). Results Out of 3502 articles, 32 observational studies (10 cohort and 22 cross-sectional) were included in the review. Total sample regarded 19321 people. In 41% of studies adherence was assessed through self-report, in 34% through interviews and in the rest (25%) adherence was measured through other methods or combined ones. 37% of selected studies were conducted in Developing and Emerging Countries (mostly African or Asiatic ones). In 58% of these studies and in 30% of studies set in Developed Countries a low level of education was found to influence HAART compliance. Conclusions Our research suggests that education attainment is an important factor to be considered in strategies aimed at improving HAART compliance in both Developing and Emerging Countries and Developed ones, although educational systems can not be compared completely. Key message: HAART compliance is a complex process in which socioeconomic determinants have to be considered in order to improve i
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