Preparing the assimilation of the future MTG‐IRS sounder into the mesoscale NWP AROME model

International audienceThe IRS (InfraRed Sounder) instrument is an infrared Fourier transform spectrometer that will be on board the Meteosat Third Generation series of the future EUMETSAT geostationary satellites. It will measure the radiance emitted by the Earth at the top of the atmosphere using 1960 channels. IRS will provide high spatial and temporal frequency 4D information on atmospheric temperature and humidity, winds, clouds, surfaces, as well as on the chemical composition of the atmosphere. The assimilation of these new observations represents a great challenge and opportunity for the improvement of Numerical Weather Prediction (NWP) forecast skill, especially for mesoscale models such as AROME at Météo‐France (Brousseau et al. 2016). The objectives of this study are to prepare for the assimilation of IRS in this system and to evaluate its impact on the forecasts when added to the currently assimilated observations. By using an Observing System Simulation Experiment (OSSE) constructed for a mesoscale NWP model. This OSSE framework makes use of synthetic observations of both IRS and the currently assimilated observing systems in AROME, constructed from a known and realistic state of the atmosphere. The latter, called the Nature Run, is derived from a long and uninterrupted forecast of the mesoscale model. These observations were assimilated and evaluated using a 1 h update cycle 3D‐Var data assimilation system over two‐month periods, one in the summer and one in the winter. This study demonstrates the benefits that can be expected from the assimilation of IRS observations into AROME NWP system. The assimilation of only 75 channels over oceans increases the total amount of observations used in the AROME 3D‐Var by about 50 %. The IRS impact in terms of forecast scores was evaluated and compared for the summer and winter periods. The main findings are that (i) over both periods the assimilation of these observations lead to statistically improved forecasts over the whole atmospheric column, (ii) for the summer season experiment, the forecast ranges up to +48h are improved, (iii) for the winter season experiment, the impact on the forecasts is globally positive but is smaller compared to the summer period and extends only to 24 h. Based on these results, it is foreseen that the addition of future IRS observations in the AROME NWP systems will significantly improve mesoscale weather forecasts

A Sativex®-like combination of phytocannabinoids as a disease-modifying therapy in a viral model of multiple sclerosis

[Background and Purpose]: Sativex® is an oromucosal spray, containing equivalent amounts of Δ9‐tetrahydrocannabinol (Δ9‐THC) and cannabidiol (CBD)‐botanical drug substance (BDS), which has been approved for the treatment of spasticity and pain associated to multiple sclerosis (MS). In this study, we investigated whether Sativex may also serve as a disease‐modifying agent in the Theiler's murine encephalomyelitis virus‐induced demyelinating disease model of MS.[Experimental Approach]: A Sativex‐like combination of phytocannabinoids and each phytocannabinoid alone were administered to mice once they had established MS‐like symptoms. Motor activity and the putative targets of these cannabinoids were assessed to evaluate therapeutic efficacy. The accumulation of chondroitin sulfate proteoglycans (CSPGs) and astrogliosis were assessed in the spinal cord and the effect of Sativex on CSPGs production was evaluated in astrocyte cultures.[Key Results]: Sativex improved motor activity – reduced CNS infiltrates, microglial activity, axonal damage – and restored myelin morphology. Similarly, we found weaker vascular cell adhesion molecule‐1 staining and IL‐1β gene expression but an up‐regulation of arginase‐1. The astrogliosis and accumulation of CSPGs in the spinal cord in vehicle‐infected animals were decreased by Sativex, as was the synthesis and release of CSPGs by astrocytes in culture. We found that CBD‐BDS alone alleviated motor deterioration to a similar extent as Sativex, acting through PPARγ receptors whereas Δ9‐THC‐BDS produced weaker effects, acting through CB2 and primarily CB1 receptors.[Conclusions and Implications]: The data support the therapeutic potential of Sativex to slow MS progression and its relevance in CNS repair.This work was supported by grants from the Ministry of the Economy and Competition SAF2010‐17501 (C. G.) and SAF2009‐11847 (J. F.‐R.), the Comunidad de Madrid, S2011/BMD‐2308, the Red Española de Esclerosis Múltiple RD12/0032/0008 (C. G.) sponsored by the Fondo de Investigación Sanitaria

The disease-modifying effects of a Sativex-like combination of phytocannabinoids in mice with experimental autoimmune encephalomyelitis are preferentially due to Δ9-tetrahydrocannabinol acting through CB1 receptors

Sativex®, an equimolecular combination of Δ-tetrahydrocannabinol-botanical drug substance (Δ-THC-BDS) and cannabidiol-botanical drug substance (CBD-BDS), is a licensed medicine that may be prescribed for alleviating specific symptoms of multiple sclerosis (MS) such as spasticity and pain. However, further evidence suggest that it could be also active as disease-modifying therapy given the immunomodulatory, anti-inflammatory and cytoprotective properties of their two major components. In this study, we investigated this potential in the experimental autoimmune encephalitis (EAE) model of MS in mice. We compared the effect of a Sativex-like combination of Δ-THC-BDS (10 mg/kg) and CBD-BDS (10 mg/kg) with Δ-THC-BDS (20 mg/kg) or CBD-BDS (20 mg/kg) administered separately by intraperitoneal administration to EAE mice. Treatments were initiated at the time that symptoms appear and continued up to the first relapse of the disease. The results show that the treatment with a Sativex-like combination significantly improved the neurological deficits typical of EAE mice, in parallel with a reduction in the number and extent of cell aggregates present in the spinal cord which derived from cell infiltration to the CNS. These effects were completely reproduced by the treatment with Δ-THC-BDS alone, but not by CBD-BDS alone which only delayed the onset of the disease without improving disease progression and reducing the cell infiltrates in the spinal cord. Next, we investigated the potential targets involved in the effects of Δ-THC-BDS by selectively blocking CB or PPAR-γ receptors, and we found a complete reversion of neurological benefits and the reduction in cell aggregates only with rimonabant, a selective CB receptor antagonist. Collectively, our data support the therapeutic potential of Sativex as a phytocannabinoid formulation capable of attenuating EAE progression, and that the active compound was Δ-THC-BDS acting through CB receptors.Peer Reviewe