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Item does not contain fulltext AIM: Little attention has been paid to the effects of compliance and prescription practice on treatment outcome in HIV-infected children. In this context, an evaluation of the role of covariates on pharmacokinetics is required to establish the impact of differences in dosing regimens. Here we investigate whether a once daily dosing regimen of lamivudine provides comparable exposure to the currently approved paediatric regimen. METHODS: A hypothetical group of 180 patients between 3 months and 12 years old was used to evaluate the impact of body weight on systemic exposure to lamivudine. Simulation scenarios were evaluated using AUC and Cmax as parameters of interest. The analysis was performed using a population pharmacokinetic model previously implemented in nonmem v.6.2. RESULTS: The simulations show that once daily dosing of lamivudine yields comparable exposure to historical values observed in children and adults, both for liquid and solid dosage forms. Simulated steady-state AUC(0-24 h) and Cmax values after once daily doses ranged respectively from 9.9 mg l(-)(1) h and 1.9 mg l(-)(1) for children lighter than 14 kg to 13.75 mg l(-)(1) h and 3.0 mg l(-)(1) for children heavier than 30 kg. These values are comparable or higher than historical values observed after once daily dosing in children and adults. CONCLUSIONS: Our findings illustrate how dosing regimens can be evaluated taking into account the effects of developmental growth on drug disposition. Most importantly, they suggest that the reduction in dosing frequency to once daily leads to comparable lamivudine exposure, as observed after administration of a twice daily dosing regimen.

Item does not contain fulltext AIM: Lamivudine is used as first line therapy in HIV-infected children. Yet, like many other paediatric drugs, its dose rationale has been based on limited clinical data, without thorough understanding of the effects of growth on drug disposition. Here we use lamivudine to show how a comprehensive population pharmacokinetic model can account for the influence of demographic covariates on exposure (i.e. AUC and Cmax ). METHODS: Data from three paediatric trials were used to describe the pharmacokinetics across the overall population. Modelling was based on a non-linear mixed effects approach. A stepwise procedure was used for covariate model building. RESULTS: A one compartment model with first order elimination best described the pharmacokinetics of lamivudine in children. The effect of weight on clearance (CL) and volume of distribution (V) was characterized by an exponential function, with exponents of 0.705 and 0.635, respectively. For a child with median body weight (17.6 kg), CL and V were 16.5 (95% CI 15.2, 17.7) l h(-)(1) and 46.0 (95% CI 42.4, 49.5) l, respectively. There were no differences between formulations (tablet and solution). The predicted AUC(0,12 h) after twice daily doses of 4 mg kg(-)(1) ranged from 4.44 mg l(-)(1) h for children 30 kg. CONCLUSIONS: The use of meta-analysis is critical to identify the correct covariate-parameter relationships, which must be assessed before a model is applied for predictive purposes (e.g. defining dosing recommendations for children). In contrast to prior modelling efforts, we show that the covariate distribution in the target population must be considered.

Adherence to antiretroviral combination therapy in children. What a difference half a day makes____ has explored the opportunities to support evidence generation and extrapolation across populations, with special focus on the selection of the dose, the optimisation of dosing regimens and the impact of patient behaviour towards antiretroviral treatment. A model-based approach for the evaluation of covariate effects and forgiveness of non-adherence, which may allow simplification of current dosing regimens taking into consideration inadequate compliance and its implication for efficacy and drug resistance, has been proposed. In conjunction with clinical trial simulations, this thesis addressed the possibility to evaluate relevant clinical scenarios and predict treatment outcome of simplified dosing regimens, taking into account the differences in the patterns of drug intake and the pharmacokinetic-pharmacodynam ic properties of antiretroviral drugs.

Cet article décrit l'impact du débroussaillement règlementaire contre l'incendie sur le potentiel mellifère des milieux forestiers dans la région PACA. Le débroussaillement diminue à la fois le nombre d'espèce mellifère, leur fréquence et leur recouvrement, particulièrement pour les espèces les plus importantes localement. Cette diminution n'est pas compensée par une légère augmentation du nombre et du recouvrement d'espèces herbacées mellifères au printemps comme en automne. Le potentiel est donc gravement affecté, et il ne se reconstitue que très lentement, puisqu'il reste faible plus de 5 ans après le traitement.

The statutory clearing against wildfires represents several dozens thousand hectares on the scale departments as the Bouches-du-Rhône and Var. In this study, we showed that in limestone based Provence this clearing is highly detrimental to vegetation melliferous potential when it is realized with heavy mechanical machines and without selectivity. This potential is almost nil during 3 years after clearing and increases only slowly afterward. The very strong decrease in the number of individuals, the size and the bloom of main melliferous species, essentially ligneous plants blooming in spring, is not compensated with a light increase of the herbaceous species and sometimes autumnal blooms. The situation seems a little less critical on acidic soils, but the study must be continued there because the number of studied site is too small. However, mechanical clearings along the public roads and networks, and in large fuelbreaks, represent only a small part of statutory clearings. Most of them concern private houses and public buildings in periurban environments, which surroundings are generally cleared manually or with lighter machines, with fewer consequences.; Le débroussaillement règlementaire obligatoire contre les incendies représente plusieurs dizaines de milliers d'hectares à l'échelle d'un département comme les bouches du Rhône et du Var. Dans cette étude, nous montrons qu'en Provence calcaire ce débroussaillement a un impact très défavorable sur le potentiel mellifère lorsqu'il est réalisé avec des engins mécaniques lourds et sans sélectivité. Ce potentiel est quasiment nul au cours des 3 années qui suivent le débroussaillement et ne remonte que très progressivement par la suite. La très forte diminution du nombre d'individus, de la taille et de la floraison des principales espèces mellifères, essentiellement des plantes ligneuses fleurissant au printemps, n'est pas compensée par une légère augmentation des mellifères herbacées et parfois des floraisons automnales. La situation semble un peu moins critique en Provence siliceuse, mais l'étude doit y être poursuivie car le nombre de site étudiés y est encore trop faible. Le débroussaillement mécanique le long des voies de communication et des réseaux publics, et dans les grandes coupures de combustible, ne représentent cependant qu'une petite partie des obligations légales de débroussaillement (OLD). Une grande majorité des surfaces concerne les habitations privées et bâtiments publics en milieux périurbains, dont les alentours sont souvent traités manuellement ou avec des engins plus légers, et des conséquences moins néfastes.

For several years, a reduction of the population of pollinators, particularly those of domestic and wild bees was observed. Since 2003, the law on the statutory clearing against fire is more strictly implemented in France, increasing cleared surfaces. Beekeepers worry about possible effects of these clearings on the production and health of their livestock. This is the framework of this study on the impact of the statutory clearings in Provence, on the nectar flora and the beekeeping potential of scrublands and of clear conifer stands. For that purpose, we assessed the effect of these clearings on the flowering quantitatively and qualitatively. The clearing reduces the cover of nectar species and the quantity of flowers, particularly for Rosmarinus officinalis. It is thus unfavourable to the nectar flora and the beekeeping potential. However, a more selective clearing would certainly contribute to limit the impacts of the clearing on the beekeeping potential.; Depuis plusieurs années, on observe une réduction des populations de pollinisateurs, notamment celles des abeilles domestiques et sauvages. Depuis 2003, la loi sur le débroussaillement réglementaire contre l'incendie est appliquée plus strictement en France, augmentant ainsi les surfaces débroussaillées. Les apiculteurs s'inquiètent d'éventuelles répercutions de ces débroussaillements sur la production et la santé de leur cheptel. C'est dans ce contexte que se situe cette étude prospective sur l'impact des débroussaillements réglementaires en Provence, sur la flore mellifère et le potentiel apicole des garrigues et des peuplements de résineux clairs. Pour cela, nous estimons notamment l'effet de ces débroussaillements sur la floraison autant d'un point de vue quantitatif que qualitatif. Le débroussaillement réduit le recouvrement des espèces mellifères et la quantité d'éléments floraux, ceci étant particulièrement vrai pour le romarin. Il est donc défavorable à la flore mellifère et au potentiel apicole. Toutefois, la sauvegarde d'alvéoles mâtures ou un débroussaillement plus sélectif contribueraient certainement à limiter les impacts du débroussaillement sur le potentiel apicole.

The objective of this manual is to improve the knowledge of the fire ignition causes and their accurate localisation. This manual made by Cemagref within the Forest Focus* framework (FF2004-06 convention about the monitoring of the forest continuum relating to the forest fire) was performed with the French partnerships (forest managers, policemen, firefighters) and the Spanish experts (EIMFOR*). It computes different methods used in Spain, Portugal, California and Australia to fit them to the French Mediterranean context. This approach relies on the method of the physical evidences which is very objective and organized in order to leave nothing to chance., Ce guide a pour objectif de participer à l'amélioration de la connaissance des causes de départ de feu ainsi qu'à leur localisation précise. Il a été réalisé par le Cemagref d'Aix-en-Provence dans le cadre de l'étude Forest Focus* (Programme FF2004-06 orienté sur le suivi continu des forêts dans le domaine des incendies de forêt), en collaboration avec les partenaires français (forestiers, gendarmes, pompiers) et espagnols (EIMFOR*) reconnus pour leur compétence dans le domaine. Il synthétise les différentes méthodes utilisées en Espagne, au Portugal mais aussi en Californie et en Australie et propose une adaptation de ces méthodes au contexte français. La démarche préconisée s'appuie sur la méthode des preuves physiques, démarche qui se veut objective et très hiérarchisée, de manière à ne rien laisser au hasard.

BACKGROUND AND PURPOSE: The wide application of embolization in the treatment of aneurysms has created the need for an intraprocedural means to anticipate a poor outcome by monitoring hemodynamic changes in the brain. METHODS: Transcranial Doppler sonography was used to monitor flow velocity in the middle cerebral artery (MCA) in 23 patients undergoing embolization with Guglielmi detachable coils (GDCs) of either incidental or symptomatic intracranial aneurysms. Sonographic values were recorded from the ipsilateral MCA at the beginning, middle, and end of the interventional procedure and 24 hours afterward. RESULTS: No complications occurred in 15 patients. In these cases, sonography showed an average decrease in MCA flow velocity of 2.7% after GDC application, returning to baseline at the end of treatment and then increasing by about 17% 24 hours later. In four patients with vasospasm on posttreatment angiograms, MCA flow velocity increased to values higher than 120 cm/s after GDC application, returning to baseline after 24 hours. In four patients with ischemic complications (two transient ischemic attacks, one stroke, one vascular death), MCA flow velocity decreased more than 30% and did not return to preoperative values within 24 hours. CONCLUSION: The application of transcranial Doppler sonographic monitoring during endovascular treatment may help to identify patients at risk for posttreatment cerebral ischemia.

Southwestern Sicily is an area of infrequent seismic activity. Only an earthquake occurred in the Belice valley on 13 January 1968 is reported in the historic earthquake catalogues (see e.g. [1]) as severe event, that is characterized by moderate-high energy (M=6.5) and significant epicentral and local macroseismic intensities (Io=X and I=VII-VIII of the MCS scale). Nevertheless, some studies (e.g. [2]) suggest that probably at least two earthquakes struck this area, between the fourth century B.C. and the early Middle Ages, with energy able to damage and produce collapse in some temples of Selinunte. In this framework, we propose the use of non-invasive approaches in geoarchaeology for detecting and measuring structural damages in walls and foundations of Selinunte Acropolis, in order to identify any effects due to historic earthquakes. The methodology consists of an integration of landscape analysis, remote sensing and geophysical methods useful for dating important ancient seismic events. The intents of this multidisciplinary research are: 1) the detailed analysis of the most important structures and the landscape, also to assess kinematics behaviour of the masonry segments and their defects (cracks, disintegration of the original mortar, replacement of ashlars, etc.) and 2) the analysis of the seismic site response in order to assess potential amplification phenomena on the ground motion. The preliminary results seem to show significant residuals on the walls on the East side of the Acropolis, where also the geological and stratigraphical setting provide amplification effects in correspondence of frequency range typical of the earthquakes and for manmade structures.