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There is a growing body of evidence that air pollution is a significant threat to health worldwide. The time exposure to air pollution leads diverse impact on the health. A short-term exposure increases hospital admission and mortality rate, causing mainly respiratory and cardiovascular diseases, including dyspnea; whereas a long-term exposure reduce life expectancy. Although the relationship between short term exposure to air pollution and several cardiovascular pathologies, such as coronaropathy, is widely established, the link regarding cardiac dyspnea is quite controversial. Nevertheless, previous studies are lead on few selected cities preventing a global overview on an entire territory. Here, we aim to fill this gap and finally establish the impact of pollution on cardiac dyspnea, using the “Région Sud” in the south of France, as a model. We focused on the period from 2013 to 2018 for which we dispose of clinical data of people having attended one of the 47 emergency departmentss of the region with symptoms related to cardiac dyspnea, collected by the gip e-santé ORUPACA, for a total of 43,404 events. We collected pollutants (NO2, PM10 and O3) and climate (temperature and pressure) measurements on a daily basis supplied by the French agency AtmoSud. We set up a reproducible statistical framework based on a distributed lag non-linear model (DLNM) to show the relationship between short term exposure to outdoor air pollution and the incidence of cardiac dyspnoea event for each of the defined 366 areas of the region. This study showed that each pollutant has a significant effect on triggering cardiac dyspnoea. Specifically, we found that the biggest cities of the region, with more than 300000 habitants, such as Marseille and Nice have a significant increase of 1,5 and 1,2 respectively, if the NO2 pass the threshold of 200 mg/m3, three days before the dyspnea event. In cities with habitants between 50000 and 100000, such as Avignon and Fréjus, we found that is the O3 to have the most significant effect on the cardiac dyspnea events. A peak of O3 over 180 mg/m3 in these cities, will increase of five times the number of dyspnea events after 6 days. We observed a milder effect of PM10 on dyspnea events and mainly on cities on the coast, such as Marseille, Nice and Toulon, for which the risk of dyspnea events significantly increase if the level of PM10 overcome 50 mg/m3. Importantly, we established the impact of three different pollutants on hospital admission for cardiac dyspnea in each of the 366 areas in the South of France. Overall, we observed that each pollutant impacts the cardiac dyspnea events on different time frame between the pollution peak and the event, such as: few days for NO2, between 6 and 8 days for O3 and the same day or the day before for PM10. Finally, we developed a user-friendly web application called HEART (Health, Environment in PACA Region Tool) to easily show the results of this study. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Idex UCAJEDI

Resume Introduction L’accident vasculaire cerebral (AVC) touche en France environ 120 000 personnes chaque annee. Le benefice de la prise en charge dans une unite neurovasculaire (UNV) a ete demontre dans de nombreuses etudes controlees. L’objectif de cette etude est d’evaluer, d’un point de vue medico-economique, l’impact de la mise en place de l’UNV de Pontoise. Patients et methodes Les donnees de cinq groupes homogenes de malades (GHM) dont le diagnostic principal est en rapport avec un AVC ont ete analysees a partir de l’etude nationale des couts (ENC). Ce travail ne concerne que les AVC et accidents ischemiques transitoires (AIT) de l’adulte et exclut les hemorragies sous-arachnoidiennes. Les parametres medicaux et economiques ont ete recueillis sur la periode de janvier a octobre 2006 et compares a ceux de la meme periode en 2005, soit avant l’ouverture de l’UNV. Resultats Trois cent vingt-trois sejours ont ete realises entre le 1er janvier et le 31 octobre 2006 et 216 a la meme periode avant l’ouverture de l’UNV, soit une augmentation d’environ 50 % de l’ensemble des sejours AVC de notre etablissement. Le taux des sejours realises en neurologie a progresse de 29 %. Il n’existait pas de difference significative entre les deux periodes en termes d’âge (mediane 69 versus 70 ans) et de sex- ratio. La duree moyenne de sejour (DMS) etait identique (neuf jours). Il n’y avait pas de difference significative concernant le taux de mortalite (5,6 % versus 6,2 %) et celui du retour a domicile (44,6 % versus 44,4 %). Le cout par sejour en 2006 etait de 3534 euros [median ; min 664–max 57 542] versus en 2005 3541 [681–35 149] (p = 0,57). L’analyse par GHM a mis en evidence une augmentation du cout pour les AVC graves, les infarctus cerebraux et les hemorragies. Pour les AIT le cout et la DMS ont diminue (ns). Conclusion L’ouverture de l’UNV s’est ainsi accompagnee d’une augmentation de l’activite sans augmentation du cout global. Cela peut etre en partie lie au peu de moyens alloues a l’ouverture de l’UNV (notamment le personnel soignant). L’ENC peut etre utilisee pour evaluer l’activite d’une UNV. Ce travail pourra etre realise sur un plus grand effectif ou dans plusieurs unites de taille differente.

In this paper, we present an innovative way of fabricating MOS transistors with totally Ni-silicided (Ni-TOSI) gates without any CMP step before the full gate silicidation process. The combination of the use of a hard-mask-capped ultra-low initial Si gate with a selective S/D epitaxy step enables us to perform the total gate and junction silicidation in one single step similarly to a standard MOS flow. Full gate silicidation and well-controlled junction silicidation is achieved down to minimum gate lengths of 40 nm. Moreover, we show that the TOSI PMOS device performances are compatible with the 45 nm-node LP requirements. Reliability data is added demonstrating that no additional breakdown mechanisms occur after the TOSI process.

In this paper we explain the advantages of very thin layers (in the channel and in the BOX) of the silicon-on-nothing (SON) transistors. Electrical results are also presented, with gate length down to 38 nm, with a conduction channel thickness as thin as 9 and 5 nm. It is also demonstrated that SON is better suited than bulk for accepting a metallic gate for low-voltage operation due to its intrinsic low threshold voltage. We have integrated midgap CoSi 2 metal gate by total gate silicidation on SON transistors with Si-conduction channel thickness down to 5 nm. Finally, we will analyse the ITRS’01 CMOS Roadmap and show that SON allows reaching the I on / I off specifications down to the 32 nm node and approaching closely those for the 22 nm node, that is by far impossible with bulk.

Objective.—To assess the effects of amitriptyline and sudden analgesic withdrawal on headache frequency and quality of life in patients suffering from chronic daily headache related to analgesics abuse. Methods.—Seventeen nondepressed patients with chronic drug-induced headache were included in a 9-week, parallel-group, randomized, double-blind, placebo-controlled study. After abrupt analgesic withdrawal, amitriptyline or an active placebo (trihexyphenidyl) was started. The primary efficacy variable was headache frequency recorded on a headache diary in the last 4 weeks of each treatment. The secondary efficacy variable was quality of life (Nottingham Health Profile). Results.—Headache frequency decreased by 45% in the amitriptyline group and by 28% in the trihexyphenidyl group. Amitriptyline enhanced all the dimensions of quality of life and significantly improved emotional reaction and social isolation. Conclusion.—This pilot study suggests a beneficial effect of amitriptyline on headache frequency and quality of life for patients with chronic drug-induced headache.

Studies in animal models show a selective D1 receptor agonist with full functional efficacy compared with dopamine to have antiparkinsonian efficacy of similar magnitude to levodopa, without the same propensity for inducing dyskinesia. To date, no such agent has been tested in humans. ABT-431 is the prodrug of A-86929, a full, selective D1 receptor agonist. Subjects (n = 14) with levodopa-responsive Parkinson's disease received five doses of ABT-431 (5, 10, 20, 30, and 40 mg) and one of placebo after a 12-hour levodopa holiday. Response was assessed by using the Unified Parkinson's Disease Rating Scale motor subsection. Dyskinesia was separately graded. ABT-431 showed efficacy significantly superior to placebo at doses of 10 mg and more, and of similar magnitude to that seen with levodopa. Dyskinesia was reduced in several patients after receiving ABT-431. There were no serious adverse events, the most common minor events being nausea and emesis, dizziness, and hypotension. Assuming that ABT-431 is not transformed in humans into an unknown active D2 metabolite, and remains selective for D1 receptors, it is the first dopamine D1 receptor agonist to demonstrate a full antiparkinsonian effect in patients with Parkinson's disease. These preliminary findings also suggest that it may exhibit a reduced tendency to provoke dyskinesia. The emergence of a well-tolerated D1 agonist should allow for the development of a better understanding of the relation between motor efficacy and dyskinesia in Parkinson's disease.

We report in this paper the fabrirication and the characterirization of FDSOI pMOSFETs with metallic source and drain exhibiting the best performance obtained so far on metallic source/drain devices, with Ion=345µA/µm and Ioff=30nA/µm at −1V for a 50nm gate length device. These results have been achieved thanks to a careful optimization of the source/drain to channel contacts, which can allow specifific contact resistivities as low as 0.1 Ω.µm2.

In this paper, we report on the solid state reactions of Ni thin films (6nm to 12nm) deposited on Ge (001). Especially, the influence of the substrate dopants (As and BF2) is investigated. TEM and SIMS analyses point out the presence of an additional phase at the NiGe/Ge interface. EELS and SIMS measurements reveal that this phase contains Ni and Ge. On the another hand, ex-situ XRD spectra allows to determine a change in NiGe texture with Ge(001) doped or undoped. In situ XRD confirms that the kinetics shifts from simultaneous to sequential growth of nickel germanides, as predicted previously. Moreover, a recrystallization of NiGe is observed only on the undoped substrate. This recrystallization can be attributed to a contribution of a stress term in addition of the surface energy. This stress term becomes minor when temperature increases and Ni-rich phase is completely consumed. The presence of dopants, probably at the NiGe/Ge interface co uld reduce this stress and thus the recrystallization.

The challenges posed by the scaling of Silicon (Si) devices make mandatory the study of new materials to overcome the physical limitations of the Si. Germanium (Ge) was actually used in the first transistors but was then abandoned in favour of Si due to difficulties in processing Ge Oxide. However, the introduction of high-K gate dielectrics makes the use of Ge possible in an advanced technology. Its benefits for MOSFET applications are important: better transport properties than with Silicon hence higher saturation currents; lower band gap hence lower supply voltages and lower power dissipation and a lattice parameter compatible with Gallium Arsenide (GaAs) epitaxy. These are the main reasons why, during the last 4 years, the interest in Ge and Ge-On-Insulator (GeOI) substrates fabrication and properties has grown. This paper is a review of the different types of Ge and GeOI substrates, their critical aspects and their new potential applications.

In this paper, we present a detailed analysis of the performance and transport characteristics in totally Ni silicided (TOSI) devices. For two different TOSI integration schemes, we study transconductance variations of TOSI devices with respect to poly-Si gated devices. We find a clear signature of process induced strain related to the total gate silicidation step which depends largely on the integration scheme used for the fabrication of the TOSI devices.

In this paper, we present an innovative way of fabricating CMOS transistors with totally Ni-silicided (Ni-TOSI) gates without using a CMP step before the full gate silicidation. The combination of the use of a hard-mask-capped ultra-low Si gate with a selective S/D epitaxy step enables us to obtain a well-behaved silicidation of the junctions and the full gate within one single step with minimal gate lengths of 40nm. Moreover, we show that the TOSI PMOS device performances are compatible with the 45nm-node LP requirements. Reliability data is added demonstrating that no additional breakdown mechanisms occur after the TOSI process.

International audience; A wide workfunction (/spl Phi//sub m/) tuning range from 4.29eV to 4.99eV using total silicidation of doped polysilicon gate with nickel is presented. As, B and P but also N, Ge, Sb, In and co-implants, have been investigated to modulate the NiSi gate workfunction by dopant pile up effect at the silicide/dielectric interface. For the first time, defectivity data on dual gate oxide are presented, in correlation with the activation annealing impact and back end of line (BEOL) thermal stress effects as well as thorough TEM observations.

An innovative 6 nm HfO/sub 2/ MIM capacitor was integrated in interconnect levels for eDRAM functions. HfO/sub 2/ layers or Al/sub 2/O/sub 3/-HfO/sub 2/ stacks were deposited by ALCVD/sup /spl reg//. Using damascene process with TiN electrodes, this method is fully compatible with copper interconnects technology. No high temperature annealing is required to obtain dielectric performances satisfying eDRAM needs: 30 fF per cell, low leakages and high reliability.

IEEE International Electron Devices Meeting, WASHINGTON, D.C., DEC 08-10, 2003; International audience; Utilizing the SON (Silicon On Nothing) process, highly performant double gate devices have been processed in a planar configuration. Two families of devices were obtained (High Performance and Low Power) with very-high Ion/Ioff trade off. Drive currents of 1954muA/mum (Ioff = 283 nA/mum) and 1333 muA/mum (Ioff = 1 nA/mum) are obtained @1.2V with Tox = 20A and Lgate = 70nm. DIBL is very well controlled, measured below 60mV for gates as short as 40nm. These features place our devices among the most performant ever reported.

Hf-family compounds have been widely studied as high k gate dielectric materials, they can be elaborated in a wide range of deposition techniques but ALD and MOCVD are the most advanced. In this contribution, the deposition of pure HfO2 is performed by Atomic Vapour Deposition, which is a sort of pulsed-mode MOCVD. The precursor, diluted into a solvent, is pulsed through specific injectors (TriJet®), micro-droplets are vaporised and distributed to the substrate through a showerhead. ATR-FTIR and Hg-probe measurements have been extensively used to evaluate the materials. The advantage of this specific MOCVD system is that it allows working within a wide range of liquid injection frequencies. Thus, we have been able to show that the frequency of injection has a huge impact on the structural and electrical properties of the material. It has been evidence that working at low frequencies is crucial in order to get good electrical behaviour. Higher temperature deposition shows also a clear benefit. An EOT of 1.15 nm with 6.10−2 A/cm2 at |Vfb| + 1 V, that is to say about 3 orders of magnitude below what is obtained with SiO2 has been obtained on capacitors with TiN gate. This is a very good achievement fore pure HfO2 deposited by MOCVD.This work has been made in the frame of MEDEA + T207 European project with the help of Air Liquide and Epichem.

In this paper, the first SON (Silicon On Nothing) devices with metal gate are presented. Extremely thin fully depleted Si-films are recognized to be integrable with single-metal gate (mid-gap) due to their intrinsically low threshold voltage. In this work we present mid-gap CoSi/sub 2/ metal gate by total gate silicidation on SON transistors with Si-conduction channel thickness down to 5 nm. Due to its architecture and to the continuity between SD areas and the bulk, SON transistors allow deep silicidation processing down to the gate oxide, meaning that no more polysilicon is left. SON PMOS devices were performed with 55 nm CoSi/sub 2/ gate length with 5 nm of Si-channel thickness, and show excellent performances (350 /spl mu/A//spl mu/m I/sub on/ with only 0.1 nA I/sub off/ at -1.4 V with T/sub ox/=20 /spl Aring/). The polydepletion is of course suppressed and the gate resistance (

In this paper, the first 80 nm SON MOSFETs are presented, demonstrating the electrical viability of the SON architecture. The transistors have a 20 nm thick Si-film channel, isolated from the bulk by a 20 nm dielectric layer. The electrical results show significant improvement (/spl sim/30%) compared with bulk reference devices. In particular, drive current and transconductance are improved due to the better effective field-inversion charge compromise, and SCE due to the thinness of the junctions and of the channel. These electrical results are then used to calibrate the ISE simulator and to make predictions on SON performances with more aggressive gate length and Tox. These predictions show the potential of the SON architecture for future CMOS generations.

A single morning dose of dual-release formulation was compared with a slow-release formulation of l-dopa plus benserazide in a randomized, double-blind, cross-over study in 16 fluctuating patients with PD. The mean time to “on” was shorter with the dual-release formulation (43 ± 31 minutes) than with the slow-release formulation (81 ± 39 minutes) (p < 0.001), whereas the mean time to relapse to “off” was similar for both formulations. The dual-release formulation had a significantly shorter time to reach peak concentration (tmax) and greater maximum concentration (Cmax) and area under the plasma concentration time curve (AUC0–5 h) than the slow-release formulation, whereas apparent elimination half-life (t1/2) was similar for both formulations.

Cholecystokinin is one of the most abundant neuropeptides in the human CNS. It coexists with dopamine in ventral tegmental and substantia nigra neurons in rodents and primates, but the coexistence is less obvious in normal humans.1 It modulates central motor effects of dopamine through nigral or striatal cholecystokinin-A (excitatory) and cholecystokinin-B (inhibitory) receptors. The effect of the neuropeptide differs, however, depending on the animal species, the dose used, cotreatments, and site of injection. Cholecystokinin is selectively decreased in the substantia nigra of patients with Parkinson's disease, and cholecystokinin-A antagonist binding is reduced in hemiparkinsonian monkeys. Cholecystokinin inhibits levodopa induced dyskinesias in parkinsonian monkeys,1 but proglumide, a cholecystokinin antagonist, did not improve motor signs in dyskinesia free patients with Parkinson's disease.2 Proglumide is, however, a weak non-selective cholecystokinin antagonist. Oral SR 27897B (SR; Sanofi Recherche), a highly selective and potent cholecystokinin-A receptor antagonist, penetrates the CNS and blocks cholecystokinin potentiation of dopaminergic neurotransmission.3 We evaluated the potential antidyskinetic effects of oral SR in parkinsonian patients using a placebo controlled double blind study design and a single challenge of apomorphine, a test used to determine the antidyskinetic properties of associated treatments.4 As cholecystokinin-A antagonism may modify gastrointestinal motility,3 and consequently the kinetics of oral …

Studies in animal models show a selective D1 receptor agonist with full functional efficacy compared with dopamine to have antiparkinsonian efficacy of similar magnitude to levodopa, without the same propensity for inducing dyskinesia. To date, no such agent has been tested in humans. ABT-431 is the prodrug of A-86929, a full, selective D1 receptor agonist. Subjects (n = 14) with levodopa-responsive Parkinson's disease received five doses of ABT-431 (5, 10, 20, 30, and 40 mg) and one of placebo after a 12-hour levodopa holiday. Response was assessed by using the Unified Parkinson's Disease Rating Scale motor subsection. Dyskinesia was separately graded. ABT-431 showed efficacy significantly superior to placebo at doses of 10 mg and more, and of similar magnitude to that seen with levodopa. Dyskinesia was reduced in several patients after receiving ABT-431. There were no serious adverse events, the most common minor events being nausea and emesis, dizziness, and hypotension. Assuming that ABT-431 is not transformed in humans into an unknown active D2 metabolite, and remains selective for D1 receptors, it is the first dopamine D1 receptor agonist to demonstrate a full antiparkinsonian effect in patients with Parkinson's disease. These preliminary findings also suggest that it may exhibit a reduced tendency to provoke dyskinesia. The emergence of a well-tolerated D1 agonist should allow for the development of a better understanding of the relation between motor efficacy and dyskinesia in Parkinson's disease.

Introduction Nous presentons un cas de xanthomatose cerebro-tendineuse d’allure sporadique, dont le diagnostic est pose apres une longue evolution. Observation Case 05/80 : Une patiente de 55 ans, mere de deux enfants, âges de 31 et 29 ans apparemment en bonne sante, presenta a l’âge de neuf ans une cataracte bilaterale. Il n’y avait pas d’autre antecedent familial connu. Des 1979 apparurent des troubles de l’equilibre responsables de chutes. L’examen neurologique retrouvait un syndrome cerebelleux statique et cinetique sans dysarthrie. A partir de 1985 s’installerent une tetraparesie predominant aux membres inferieurs, des troubles proprioceptifs, vesico-sphincteriens et cognitifs. Par la suite il fut note, une deformation des 2 pieds en equin et des diarrhees recurrentes. Le reste de l’examen neurologique et somatique etait sans particularite. Le bilan biologique, les serologies virales, l’etude du LCR, les dosages hormonaux, vitaminique et metabolique etaient normaux, la recherche d’acanthocytose negative. L’imagerie par resonance magnetique nucleaire montra une atrophie cerebelleuse, des calcifications des noyaux denteles sans atteinte des noyaux gris centraux. Le dosage du cholestanol fut realise en 2006 et montra un taux eleve : 1,4/100 (normal : 1/1000). Le diagnostic de xanthomatose cerebro-tendineuse fut porte. Un traitement a base d’acide chenodeoxycholique fut instaure plusieurs annees apres. Discussion Diverses affections neurologiques dont une sclerose en plaque et une atrophie multisystematisee ont ete evoquees. L’errance et le retard diagnostic sont probablement lies a la rarete de cette affection. Les xanthomes tendineux sont retrouves dans 70 p. 100 des cas et leur absence ne doit pas ecarter le diagnostic. Conclusion Ce cas illustre la necessite d’evoquer le diagnostic xanthomatose cerebro-tendineuse devant une cataracte precoce associee a une symptomatologie cerebelleuse et des diarrhees chroniques, meme en absence de xanthome.

Introduction Nous presentons un cas de neurosarcoidose a manifestation meningee. Observation Dossier n 10/05 : Une patiente de 65 ans, originaire du Cap Vert, mere de 5 enfants, presenta 5 mois avant son hospitalisation des cephalees d’installation progressive associees a un trouble de l’equilibre et une hypoacousie gauche. L’interrogatoire revela une toux seche chronique et des arthralgies. Ses antecedents etaient marques par une tuberculeuse pulmonaire traitee dans l’enfance. Le reste de l’examen neurologique et somatique fut sans particularite. Le bilan biologique trouva une VS a 85 mm la 1 re heure. L’analyse du LCR montra 27 elements lymphocytaires/mm 3 , une proteinorachie a 0,65 g/l. le reste du bilan inflammatoire, infectieux et immunologique (serologie syphlis, HIV, facteur anti nucleaire, enzyme de conversion, electrophorese des proteines seriques et complement), fut normal en dehors des ANCA > 10, type MPO. L’IDR a la tuberculine fut positive. Le scanner thoracique, la biopsie des glandes salivaires, l’EMG furent normaux. L’IRM cerebrale objectiva un epaississement meninge, a predominance sous tentorielle et prenant le contraste. Le parenchyme cerebral ne montra pas d’anomalie. Discussion Le diagnostic de tuberculose basilaire fut evoque et un traitement d’epreuve est instaure pendant 2 mois sans amelioration. Devant la negativite du bilan de controle (enzyme de conversion, biopsie osteo-medullaire et lavage broncho-alveolaire), on pratiqua une biopsie meningee qui objectiva des granulomes histiocytaires epithelioides sans cellule geante, sans necrose caseeuse. Une corticotherapie fut instauree permettant une amelioration clinique Conclusion Ce cas illustre bien l’apport diagnostique de la biopsie meningee dans les pachymeningites chroniques isolees.

In this paper, we demonstrate for the first time full integration of highly performant NMOS and PMOS silicon-on-nothing (SON) devices into circuits. We demonstrated fully functional SRAMs cells with very good yield, showing static noise margin (SNM) of 175mV and write margin (WM, stable "read 0") above 500mV. The optimized SON devices show performance for NMOS and for PMOS that is among the best published data (with drive current up to 1100/350/spl mu/A//spl mu/m for 138/20nA//spl mu/m I/sub off/ for NMOS and PMOS devices respectively @V/sub dd/=1.2V, I/sub ox/=16A). Finally, we present also the implementation of the SON process into a new "localized SOI" architecture on bulk. This new and simplified SON process is also demonstrated by fully operational SRAM cells.

In this paper, we present a CMOS NiSi totally silicided (TOSI)-gate on SiON module, based on a single step silicidation of the junctions and the total gate, and demonstrate its industrial feasibility on SRAM demonstrators. The single step silicidation is achieved by the use of an ultra-low initial Si gate electrode and selective S/D epitaxy, which allows us to avoid any additional CMP step. We show excellent transistor morphology, good device results and first functional NiSi TOSI-gate SRAMs in a state-of-the-art industrial cell size indicating the potential of our TOSI integration module for LP applications

In this paper, we demonstrate for the first time a new original approach of the integration of dual phase TOtally Silicided (TOSI) Gates using a close-to-standard CMOS flow without any additional CMP step targeting the use of NiSi for NMOS and Ni2Si for the PMOS gate electrode on High-K dielectrics. The impact of the TOSI-process on the gate stack characteristics is investigated in detail on capacitance, gate leakage and work function dota. With respect to poly-Si gated devices we find a significant reduction of the effective oxide thickness in inversion without degradation of the gate leakage statistics. The results emphasize the potential of the integration of TOSI-gates on high-K gate oxides.

Dyskinesia is a frequent and disabling side effect in patients with Parkinson's disease treated with chronic dopatherapy. Preclinical data in the 1-methyl-4-phenyl-1,2,3,6,-tetrahydropyridine (MPTP) monkey suggest that alpha-2 antagonists may reduce dihydroxyphenylalanine (L-DOPA)-induced dyskinesia. We assessed, in a pilot randomised placebo-controlled study, the effects of single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan, an alpha-2 antagonist, on motor parkinsonian disability and L-DOPA-induced dyskinesia following an acute oral challenge of L-DOPA in 18 patients with Parkinson's disease. The severity of L-DOPA-induced dyskinesia improved after 20 mg idazoxan pretreatment, while there was no concommittant deterioration in the antiparkinsonian response to L-DOPA. These results suggest that blocking alpha-2 receptors in patients with Parkinson's disease might improve L-DOPA-induced dyskinesia without the cost of a return of parkinsonian symptomatology. Further studies are required to assess whether this property could have potential therapeutic applications in the long-term management of dyskinetic patients with Parkinson's disease. © 2001 Movement Disorder Society.

We thank Frédérique Laurent-Nègre for her comments and revisions, Joel Dupays for useful discussions and O. Simonin for fruitful discussions which have motivated the writing of Section 2.2.; International audience; The accurate simulation of disperse two-phase flows, where a discrete partic- ulate condensed phase is transported by a carrier gas, is crucial for many applications; Eulerian approaches are well suited for high performance computations of such flows. However when the particles from the disperse phase have a significant inertia compared to the time scales of the flow, particle trajectory crossing (PTC) occurs i.e. the particle ve- locity distribution at a given location can become multi-valued. To properly account for such a phenomenon many Eulerian moment methods have been recently proposed in the literature. The resulting models hardly comply with a full set of desired criteria involving: 1- ability to reproduce the physics of PTC, at least for a given range of particle inertia, 2- well-posedness of the resulting set of PDEs on the chosen moments as well as guaran- teed realizability, 3- capability of the model to be associated with a high order realizable numerical scheme for the accurate resolution of particle segregation in turbulent flows. The purpose of the present contribution is to introduce a multi-variate Anisotropic Gaus- sian closure for such particulate flows, in the spirit of the closure that has been suggested for out-of-equilibrium gas dynamics and which satisfies the three criteria. The novelty of the contribution is three-fold. First we derive the related moment systems of conservation laws with source terms, and justify the use of such a model in the context of high Knudsen numbers, where collision operators play no role. We exhibit the main features and advan- tages in terms of mathematical structure and realizability. Then a second order accurate and realizable MUSCL/HLL scheme is proposed and validated. Finally the behavior of the method for the description of PTC is thoroughly investigated and its ability to account accurately for inertial particulate flow dynamics in typical configurations is assessed.

International audience; In the present work, the Eulerian Large Eddy Simulation of dilute disperse phase flows is investigated. By highlighting the main advantages and drawbacks of the available approaches in the literature, a choice is made in terms of modelling: a Fokker-Planck-like filtered kinetic equation proposed by Zaichik et al. 2009 and a Kinetic-Based Moment Method (KBMM) based on a Gaussian closure for the NDF proposed by Vie et al. 2014. The resulting Euler-like system of equations is able to reproduce the dynamics of particles for small to moderate Stokes number flows, given a LES model for the gaseous phase, and is representative of the generic difficulties of such models. Indeed, it encounters strong constraints in terms of numerics in the small Stokes number limit, which can lead to a degeneracy of the accuracy of standard numerical methods. These constraints are: 1/as the resulting sound speed is inversely proportional to the Stokes number, it is highly CFL-constraining, and 2/the system tends to an advection-diffusion limit equation on the number density that has to be properly approximated by the designed scheme used for the whole range of Stokes numbers. Then, the present work proposes a numerical scheme that is able to handle both. Relying on the ideas introduced in a different context by Chalons et al. 2013: a Lagrange-Projection, a relaxation formulation and a HLLC scheme with source terms, we extend the approach to a singular flux as well as properly handle the energy equation. The final scheme is proven to be Asymptotic-Preserving on 1D cases comparing to either converged or analytical solutions and can easily be extended to multidimensional configurations, thus setting the path for realistic applications.

International audience; The simulation of the interaction of two simultaneously propagating air streamers of the same polarity is presented. A parametric study has been carried out using an accurate numerical method which ensures a time-space error control of the solution. For initial separation of both streamers smaller or comparable to the longest characteristic absorption length of photoionization in air, we have found that the streamers tend to merge at the moment when the ratio between their characteristic width and their mutual distance reaches a value of about 0.35 for positive streamers, and 0.4 for negative ones. Moreover it is demonstrated that these ratios are practically independent of the applied electric field, the initial seed configuration, and the pressure.

We tackle the numerical simulation of reaction-diffusion equations modeling multi-scale reaction waves. This type of problem induces peculiar difficulties and potentially large stiffness which stem from the broad spectrum of temporal scales in the nonlinear chemical source term as well as from the presence of steep spatial gradients in the reaction fronts, spatially very localized. In this paper, we introduce a new resolution strategy based on time operator splitting and space adaptive multiresolution in the context of very localized and stiff reaction fronts. The paper considers a high order implicit time integration of the reaction and an explicit one for the diffusion term in order to build a time operator splitting scheme that exploits efficiently the special features of each problem. Based on recent theoretical studies of numerical analysis such a strategy leads to a splitting time step which is restricted by neither the fastest scales in the source term nor by stability constraints of the diffusive steps but only by the physics of the phenomenon. We aim thus at solving complete models including all time and space scales within a prescribed accuracy, considering large simulation domains with conventional computing resources. The efficiency is evaluated through the numerical simulation of configurations which were so far out of reach of standard methods in the field of nonlinear chemical dynamics for two-dimensional spiral waves and three-dimensional scroll waves, as an illustration. Future extensions of the proposed strategy to more complex configurations involving other physical phenomena as well as optimization capability on new computer architectures are discussed.

http://www.stanford.edu/group/ctr/ResBriefs/2011/; International audience; In this work we are concerned with the the numerical simulation of flames issued from combustion applications with a time-space adaptive technique. This study is carried out in a classical context of laminar flames interacting with vortex structures including self-ignition processes of reactive mixtures. Hydrodynamics are decoupled from transport equations by adopting a standard thermo-diffusive approach. In this context and for the considered application, adaptive space meshing is advantageous because of the presence of localized fronts, whereas the important transient phases owing to the imposed velocity fields, as well as sudden physical variations given by the ignition of the mixture, require an adequate time adaptation in order to efficiently describe these phenomena. The coupling of an adaptive splitting technique with adaptive multiresolution in space allows a very efficient approach and leads to detailed numerical simulations in 2D and 3D with standard computer ressources.

This paper presents a new resolution strategy for multi-scale streamer discharge simulations based on a second order time adaptive integration and space adaptive multiresolution. A classical fluid model is used to describe plasma discharges, considering drift-diffusion equations and the computation of electric field. The proposed numerical method provides a time-space accuracy control of the solution, and thus, an effective accurate resolution independent of the fastest physical time scale. An important improvement of the computational efficiency is achieved whenever the required time steps go beyond standard stability constraints associated with mesh size or source time scales for the resolution of the drift-diffusion equations, whereas the stability constraint related to the dielectric relaxation time scale is respected but with a second order precision. Numerical illustrations show that the strategy can be efficiently applied to simulate the propagation of highly nonlinear ionizing waves as streamer discharges, as well as highly multi-scale nanosecond repetitively pulsed discharges, describing consistently a broad spectrum of space and time scales as well as different physical scenarios for consecutive discharge/post-discharge phases, out of reach of standard non-adaptive methods., Comment: Support of Ecole Centrale Paris is gratefully acknowledged for several month stay of Z. Bonaventura at Laboratory EM2C as visiting Professor. Authors express special thanks to Christian Tenaud (LIMSI-CNRS) for providing the basis of the multiresolution kernel of MR CHORUS, code developed for compressible Navier-Stokes equations (D\'eclaration d'Invention DI 03760-01). Accepted for publication; Journal of Computational Physics (2011) 1-28

Special Issue on Splitting Methods for Differential Equations; International audience; In this paper we study the approximation by splitting techniques of the ordinary differential equation Udot+A U+B U=0, U(0)=U0 with A and B two matrices. We assume that we have a stiff problem in the sense that A is ill-conditionned and U0 is a vector which is the discretization of a function with a very high derivative. This situation may appear for example when we study the discretization of a partial differential equation. We prove some error estimates for two general matrices and in the stiff case, where the estimates are independent of U0 and the commutator between A and B. This paper is dedicated to Michel Crouzeix.

In this paper, we perform the numerical analysis of operator splitting techniques for nonlinear reaction-diffusion systems with an entropic structure in the presence of fast scales in the reaction term. We consider both linear diagonal and quasi-linear non-diagonal diffusion; the entropic structure implies the well-posedness and stability of the system as well as a Tikhonov normal form for the nonlinear reaction term [23]. It allows to perform a singular perturbation analysis and to obtain a reduced and well- posed system of equations on a partial equilibrium manifold as well as an asymptotic expansion of the solution. We then conduct an error analysis in this particular framework where the time scale associated to the fast part of the reaction term is much shorter that the splitting time step $\Delta t$, thus leading to the failure of the usual splitting analysis techniques. We define the con- ditions on diffusion and reaction for the order of the local error associated with the time splitting to be reduced or to be preserved in the presence of fast scales. All the results obtained theoretically on local error estimates are then illustrated on a numerical test case where the global error clearly reproduces the scenarios foreseen at the local level. We finally investigate the discretiza- tion of the corresponding problems and its influence on the splitting error in terms of the previously conducted numerical analysis.