FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination.

BackgroundFTY720 (fingolimod) is the first oral drug approved by the Food and Drug Administration for treatment of patients with the relapsing-remitting form of the human demyelinating disease multiple sclerosis. Evidence suggests that the therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes into the central nervous system (CNS). We hypothesized that FTY720 treatment would affect lymphocyte migration to the CNS and influence disease severity in a mouse model of viral-induced neurologic disease.MethodsMice were infected intracranially with the neurotropic JHM strain of mouse hepatitis virus. Infected animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and morbidity and mortality recorded. Infiltration of inflammatory virus-specific T cells (tetramer staining) into the CNS of FTY720-treated mice was determined using flow cytometry. The effects of FTY720 treatment on virus-specific T cell proliferation, cytokine production and cytolytic activity were also determined. The severity of neuroinflammation and demyelination in FTY720-treated mice was examined by flow cytometry and histopathologically, respectively, in the spinal cords of the mice.ResultsAdministration of FTY720 to JHMV-infected mice resulted in increased clinical disease severity and mortality. These results correlated with impaired ability to control viral replication (P < 0.05) within the CNS at days 7 and 14 post-infection, which was associated with diminished accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS. Reduced neuroinflammation in FTY720-treated mice correlated with increased retention of T lymphocytes within draining cervical lymph nodes (P < 0.05). Treatment with FTY720 did not affect virus-specific T cell proliferation, expression of IFN-γ, TNF-α or cytolytic activity. FTY720-treated mice exhibited a reduction in the severity of demyelination associated with dampened neuroinflammation.ConclusionThese findings indicate that FTY720 mutes effective anti-viral immune responses through impacting migration and accumulation of virus-specific T cells within the CNS during acute viral-induced encephalomyelitis. FTY720 treatment reduces the severity of neuroinflammatory-mediated demyelination by restricting the access of disease-causing lymphocytes into the CNS but is not associated with viral recrudescence in this model

How to promote innovation and interdisciplinarity in organic food and farming research evaluation

The development of organic food and farming research calls for system-oriented, innovative, interdisciplinary approaches. The process of evaluating research proposals is a crucial step towards this objective. Based on the EU CORE Organic pilot call for joint transnational research projects, we analysed to what extent the evaluation criteria and procedures implemented address this issue. Feedback on the experience of the target groups involved in this call was gathered and discussed in relation to findings from the literature. Our results show that interdisciplinary and innovative aspects could be better addressed, and evaluation criteria more clearly defined and delimited. This entails reshaping the main criteria and developing more suitable evaluation categories and sub-criteria. We also suggest creating mechanisms to enable funding of a few “risky” research projects, to facilitate entry of newcomers to the arena, to promote exploratory research projects and to support longitudinal interaction among applicants and assessors

Preliminary assessment of a new SoDa service for real-time estimates and short-term forecasts of the solar radiation

International audienceMeteosat images are routinely processed at Transvalor / MINES ParisTech for assessing the solar radiation at ground by the means of the Heliosat-2 method. So far, Heliosat-2 was launched every night to update the HelioClim-3 (HC3) database with the images collected during the day. HC3 data were thus available so far at d-1. Several requirements were made by customers of HC3 for a real-time and forecast capability for horizons up to 2 h. It would help in managing the PV plants or intelligent buildings, and eventually increasing the financial gains. The major challenges to develop such a capability were pertaining to the scientific domain in order to find an accurate method, and to operational constraints. The constraints are on both sides: provider and customer. The method should be fast enough to enable the processing of large areas such as Europe, and its outputs should be such as they can be directly ingested in the own processes of the customers. The selected model is based on a local persistence and has been validated against in situ measurements. A prototype has been set up and tested for several weeks by 15 customers. The customers used the outputs of this prototype as inputs to their own processes and made their own validation by comparing the results against measurements of, e.g. PV yield. The feedback gathered from testers was overall positive and a new operational service was set up based on the prototype (http://www.soda-pro.com/soda-products/real-time-and-forecast). Further validation campaigns are planned during the second semester of 2015, either by comparing to ground measurements or performed by users with their own criteria

High spatial resolution solar atlas in Provence-Alpes-Cote d'Azur

International audienceConsidering the spatial resolution of satellite-based databases of surface solar irradiation such as HelioClim-3, the geographic scale of solar mapping that can be derived is approx. 1 / 5 000 000. This geographic scale is suitable for continent or country solar mapping. Nevertheless, customers' feedback notably states that there is a need of spatial resolution improvement. In this context of spatial resolution improvement of solar resource estimation, the project solar atlas in Provence-Alpes-Côte d'Azur (PACA), finalized in December 2010, aims at increasing spatial resolution of HelioClim-3 to derive 250 m resolution solar maps. The solar atlas accounts for the global, direct and diffuse on inclined plane or in normal incidence irradiations and their temporal variations intra and inter-annual, on a monthly basis, since February 2004. The Digital Elevation Model SRTM-V4 is used to get topographic data with a spatial resolution of approximately 100 m and a localization accuracy of typically 10 m. This topographic data is used to estimate high resolution terrain effects on HelioClim-3 derived solar radiation fields, taking into account orographic effects: * Effects of optical path length variations due to terrain elevation; * Shadow effects on direct and circumsolar diffuse radiation computed from local horizon estimation; * Horizon effects on isotropic diffuse radiation with the sky view factor estimation. These orographic phenomena are indeed the source of significant local spatial variations in solar radiation values and potentially discriminating in choosing the location, the calculation of profitability or the sizing of photovoltaic or thermodynamic solar power systems. Solar mapping with a geographic scale of 1 / 3 000 000 or more does not represent properly these local phenomena. In order to establish an accurate mapping at 250 m with associated uncertainty using HelioClim-3 data, procedures of calibration has been established with meteorological ground stations. The global horizontal irradiation is calibrated thanks to the Météo France meteorological network comprising, in PACA, about 30 automatic ground stations delivering at least daily global irradiation on horizontal plane. A strict data quality control has been applied to these ground data to guarantee their quality as reference ground-based daily irradiation data. The diffuse and direct irradiations are calibrated thanks to three specific ground stations dedicated expressly to the project, delivering one year of simultaneous 10-min global and diffuse irradiations on the horizontal plan and direct irradiation on normal incidence. Statistical analysis of direct and cross-validation estimation errors after calibration with the pyranometric ground stations has been made to establish the uncertainties associated with the solar atlas. The root mean square error of monthly irradiation estimation is about 5% (c. 5 kWh / m2) for global, direct and diffuse components on horizontal plane, without significant bias error. The accuracy of monthly direct normal irradiation is about 10% (c. 15 kWh/m2). Data from the solar atlas in PACA is available for free at www.atlas-solaire.fr. In particular, a Web Map Service (WMS), based on the Open Geographical Consortium standards, has been set up to deliver maps from the solar atlas in an interoperable and standard way

Validation of three satellite-derived databases of surface solar radiation using measurements performed at 42 stations in Brazil

International audienceThe SoDa website (www.soda-pro.com) is populated with numerous solar-related Web services. Among them, three satellite-derived irradiation databases can be manually or automatically accessed to retrieve radiation values within the geographical coverage of the Meteosat Second Generation (MSG) satellite: the two most advanced versions of the HelioClim-3 database (versions 4 and 5, respectively HC3v4 and HC3v5), and the CAMS radiation service. So far, these databases have been validated against measurements of several stations in Europe and North Africa only. As the quality of such databases depends on the geographical regions and the climates, this paper extends this validation campaign and proposes an extensive comparison on Brazil and global irradiation received on a horizontal surface. Eleven stations from the Brazilian Institute of Space Research (INPE) network offer 1 min observations, and thirty-one stations from the Instituto Nacional de Meteorologia (INMET) network offer hourly observations. The satellite-derived estimates have been compared to the corresponding observations on hourly, daily and monthly basis. The bias relative to the mean of the measurements for HC3v5 is mostly comprised between 1 and 3 %, and that for HC3v4 between 2 and 5 %. These are very satisfactory results and they demonstrate that HC3v5, and to a lesser extent HC3v4, may be used in studies of long-term changes in SSI in Brazil. The situation is not so good with CAMS radiation service for which the relative bias is mostly comprised between 5 and 10 %. For hourly irradiation, the relative RMSE ranges from 15 to 33 %. The correlation coefficient is very large for all stations and the three databases, with an average of 0.96. The three databases reproduce well the hour from hour changes in SSI. The errors show a tendency to increase with the viewing angle of the MSG satellite. They are greater in tropical areas where the relative humidity in the atmosphere is important. It is concluded that except for the overestimation by CAMS radiation service, the three databases are suitable for studies of the solar resources in Brazil

Pain Intervention for people with Dementia in nursing homes (PID) : study protocol for a quasi-experimental nurse intervention

Background: It is estimated that 19 to 83% of people with dementia suffer from pain that is inadequately treated in the last months of life. A large number of healthcare workers who care for these people in nursing homes lack appropriate expertise and may therefore not always recognise, assess and treat pain in those with dementia who have complex problems on time, properly and efficiently. The aim of this intervention trial is to identify care needs of people with dementia suffering from pain living in a nursing home. Methods: A quasi-experimental nurse-led intervention trial based on a convenience sample of four nursing homes in the Swiss Canton of Zurich examines the effects on dementia patients (n = 411), the healthcare institution and the qualification level of the healthcare workers compared to historical controls, using an event analysis and a multilevel analysis. Healthcare workers will be individually trained how to assess, intervene and evaluate acute and chronic pain. There are three data-monitoring cycles (T0, T1, T2) and two intervention cycles (I1, I2) with a total study duration of 425 days. There is also a process evaluation based on Dobbins analyses that analyze in particular the potentials for change in clinical practice of change agents. Discussion: The aim of the intervention trial is to improve pain management strategies in older people with dementia in nursing homes. Clinically significant findings will be expected that will help reduce suffering in the sense of “total pain” for people with dementia. The joint intra- and interdisciplinary collaboration between practice and supply-oriented (nursing) research will have both a lasting effect on the efficiency measurement and provide scientifically sound results. Nursing homes can integrate the findings from the intervention trial into their internal quality control process. The potential for improvements can be directly influenced by the nursing home itself

Influence of Post-Welding Heat Treatment on the Corrosion Behavior of a 2050-T3 Aluminum-Copper-Lithium Alloy Friction Stir Welding Joint

The corrosion behavior of a Friction Stir Welding joint in 2050-T3 Al-Cu-Li alloy was studied in 1 M NaCl solution and the influence of T8 post-welding heat treatment on its corrosion susceptibility was analyzed. After exposure to 1 M NaCl solution, the heat affected zone (HAZ) of the weld without post-welding heat treatment was found to be the most extensively corroded zone with extended intergranular corrosion damage while, following T8 post-welding heat treatment, no intergranular corrosion was observed in the HAZ and the global corrosion behavior of the weld was significantly improved. The corrosion damage observed on the welded joints after immersion in 1 M NaCl solution was compared to that obtained after 750 h Mastmaasis Wet Bottom tests. The same corrosion damage was observed. Various stationary electrochemical tests were carried out on the global welded joint and/or each of the metallurgical zones of the welded joint to understand the corrosion damage observed. TEM observations helped in bringing meaningful elements to analyze the intrinsic electrochemical behavior of the different zones of the weld related to their microstructure. However, galvanic coupling tests showed that galvanic coupling effects between the different zones of the weld were at least partially responsible for its corrosion behavior