200 research outputs found

    Considerazioni sulla necessita di un approccio integrato tra medicina veterinaria e medicina umana nelle strategie di prevenzione della West Nile Disease in Regione Toscana.

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    La West Nile Disease (WND) è una zoonosi causata dal West Nile Virus (WNV), un Arbovirus neuropatogeno trasmesso principalmente da zanzare ornitofile isolato per la prima volta in Uganda nel 1937 e responsabile di meningo-encefalite nell'uomo e negli equidi. Il primo focolaio italiano di WND si è manifestato in Regione Toscana nel 1998 nell'area lacustre del Padule di Fucecchio nella quale si verificarono casi clinici in 14 cavalli, 6 dei quali con esito mortale, ma senza interessare l'uomo. A distanza di 10 anni dalla prima notifica, nell'agosto 2008, la WND è ricomparsa in Italia nell'area del delta del Po ma, al contrario di quanto avvenne in Toscana, l'infezione del 2008 ha causato sintomatologia clinica, oltre che nei cavalli, anche in 8 persone. Nel 2009 l'infezione si è ripresentata di nuovo in Regione Toscana con 10 cavalli risultati positivi al WNV confinati nella Provincia di Arezzo: sempre nel 2009, nell'area del delta del Po si verificarono 18 casi clinici nell'uomo 4 dei quali con esito mortale. A fronte della diffusione del virus e del cambiamento della situazione epidemiologica nel territorio toscano, si rende necessaria un'analisi delle azioni di controllo che si stanno attuando da alcuni anni, sia in medicina veterinaria che umana, per ridefinire in maniera integrata le strategie di controllo nei confronti di questa malattia (e anche di altre zoonosi) in una prospettiva “One Health”. Tale esigenza nasce dalla necessità di superare il concetto di malattia “esotica” perché, a fronte dell'aumento della popolazione umana, della globalizzazione, degli scambi commerciali e dei cambiamenti climatici, malattie come la WND, oggi “esotiche” non lo sono più. In un mondo ormai sempre più globalizzato nelle sue manifestazioni, nessuna singola disciplina o settore della società ha conoscenze o risorse sufficienti per affrontare da sola i problemi legati alla salute delle persone e degli animali od all’integrità degli ecosistemi. L''iniziativa “One Medicine – One Health”, termine coniato dal medico veterinario e parassitologo Calvin W. Schwabe (1927–2006), è una cornice logica che promuove la collaborazione tra diverse discipline affinché lavorino insieme stabilendo un approccio integrato (olistico) alla prevenzione della salute. Partendo dai dati fruibili dagli attuali sistemi informativi, l'obiettivo del presente lavoro è stato quello di illustrare considerazioni su vari aspetti relativi alla gestione della WND sia in campo umano che veterinario con l'intento di fornire spunti di riflessione per la costruzione di un sistema di sorveglianza integrato e, sopratutto, interattivo nello scambio delle informazioni in modo tale da essere in grado non solo di individuare tempestivamente la circolazione virale ma sopratutto di prevenire lo stato di malattia nell'uomo e negli animali. In tal senso, la collaborazione tecnico-scientifica tra medico-chirurgo, medico veterinario e altre professioni coinvolte, rappresenta un punto cardine sul quale lavorare per cercare di migliorare significativamente la salute umana e animale

    Dealing with mobility: Understanding access anytime, anywhere

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    The rapid and accelerating move towards the adoption and use of mobile technologies has increasingly provided people and organisations with the ability to work away from the office and on the move. The new ways of working afforded by these technologies are often characterised in terms of access to information and people ‘anytime, anywhere’. This paper presents a study of mobile workers that highlights different facets of access to remote people and information, and different facets of anytime, anywhere. Four key factors in mobile work are identified from the study: the role of planning, working in ‘dead time’, accessing remote technological and informational resources, and monitoring the activities of remote colleagues. By reflecting on these issues, we can better understand the role of technology and artefact use in mobile work and identify the opportunities for the development of appropriate technological solutions to support mobile workers

    The microtubule-based motor Kar3 and plus end–binding protein Bim1 provide structural support for the anaphase spindle

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    In budding yeast, the mitotic spindle is comprised of 32 kinetochore microtubules (kMTs) and ∼8 interpolar MTs (ipMTs). Upon anaphase onset, kMTs shorten to the pole, whereas ipMTs increase in length. Overlapping MTs are responsible for the maintenance of spindle integrity during anaphase. To dissect the requirements for anaphase spindle stability, we introduced a conditionally functional dicentric chromosome into yeast. When centromeres from the same sister chromatid attach to opposite poles, anaphase spindle elongation is delayed and a DNA breakage-fusion-bridge cycle ensues that is dependent on DNA repair proteins. We find that cell survival after dicentric chromosome activation requires the MT-binding proteins Kar3p, Bim1p, and Ase1p. In their absence, anaphase spindles are prone to collapse and buckle in the presence of a dicentric chromosome. Our analysis reveals the importance of Bim1p in maintaining a stable ipMT overlap zone by promoting polymerization of ipMTs during anaphase, whereas Kar3p contributes to spindle stability by cross-linking spindle MTs

    The valence-fluctuating ground state of plutonium

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    A central issue in material science is to obtain understanding of the electronic correlations that control complex materials. Such electronic correlations frequently arise because of the competition of localized and itinerant electronic degrees of freedom. Although the respective limits of well-localized or entirely itinerant ground states are well understood, the intermediate regime that controls the functional properties of complex materials continues to challenge theoretical understanding. We have used neutron spectroscopy to investigate plutonium, which is a prototypical material at the brink between bonding and nonbonding configurations. Our study reveals that the ground state of plutonium is governed by valence fluctuations, that is, a quantum mechanical superposition of localized and itinerant electronic configurations as recently predicted by dynamical mean field theory. Our results not only resolve the long-standing controversy between experiment and theory on plutonium’s magnetism but also suggest an improved understanding of the effects of such electronic dichotomy in complex materials.JRC.E.6-Actinide researc

    Simulations of the Static Friction Due to Adsorbed Molecules

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    The static friction between crystalline surfaces separated by a molecularly thin layer of adsorbed molecules is calculated using molecular dynamics simulations. These molecules naturally lead to a finite static friction that is consistent with macroscopic friction laws. Crystalline alignment, sliding direction, and the number of adsorbed molecules are not controlled in most experiments and are shown to have little effect on the friction. Temperature, molecular geometry and interaction potentials can have larger effects on friction. The observed trends in friction can be understood in terms of a simple hard sphere model.Comment: 13 pages, 13 figure

    Ancillary Therapy and Supportive Care of Chronic Graft-versus-Host Disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: V. Ancillary Therapy and Supportive Care Working Group Report

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    AbstractThe Ancillary Therapy and Supportive Care Working Group had 3 goals: (1) to establish guidelines for ancillary therapy and supportive care in chronic graft-versus-host disease (GVHD), including treatment for symptoms and recommendations for patient education, preventive measures, and appropriate follow-up; (2) to provide guidelines for the prevention and management of infections and other common complications of treatment for chronic GVHD; and (3) to highlight the areas with the greatest need for clinical research. The definition of “ancillary therapy and supportive care” embraces the most frequent immunosuppressive or anti-inflammatory interventions used with topical intent and any other interventions directed at organ-specific control of symptoms or complications resulting from GVHD and its therapy. Also included in the definition are educational, preventive, and psychosocial interventions with this same objective. Recommendations are organized according to the strength and quality of evidence supporting them and cover the most commonly involved organs, including the skin, mouth, female genital tract, eyes, gastrointestinal tract, and lungs. Recommendations are provided for prevention of infections, osteoporosis, and steroid myopathy and management of neurocognitive and psychosocial adverse effects related to chronic GVHD. Optimal care of patients with chronic GVHD often requires a multidisciplinary approach

    Multicentre comparison of a diagnostic assay: Aquaporin-4 antibodies in neuromyelitis optica

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    Objective Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). Methods Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1). Results Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples. Conclusions The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology

    The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

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    More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

    A Multicenter Pilot Evaluation of the National Institutes of Health Chronic Graft-versus-Host Disease (cGVHD) Therapeutic Response Measures: Feasibility, Interrater Reliability, and Minimum Detectable Change

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    The lack of standardized criteria for measuring therapeutic response is a major obstacle to the development of new therapeutic agents for chronic graft-versus-host disease (cGVHD). National Institutes of Health (NIH) consensus criteria for evaluating therapeutic response were published in 2006. We report the results of four consecutive pilot trials evaluating the feasibility and estimating the inter-rater reliability and minimum detectable change of these response criteria
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