Summary:Purpose: To evaluate the efficacy and tolerability of levetiracetam (LEV, Keppra) as add-on therapy in patients with refractory partial seizures.Methods: In this European multicenter, double-blind, randomized, placebo-controlled trial, LEV (500 or 1,000 mg twice daily) was compared with placebo as add-on therapy in 324 patients with uncontrolled simple or complex partial seizures, or both, with or without secondary generalization. After enrollment, three parallel groups were assessed during a baseline period of 8 or 12 weeks, followed by a 4-week titration interval and a 12-week evaluation period.Results: LEV significantly decreased partial seizure frequency compared with placebo. A reduction in seizure frequency of 250% occurred in 22.8% of patients in the 1,000-mg group and 3 1.6% of patients in the 2,000-mg group, compared with 10.4% of patients in the placebo group. Administration of LEV did not affect plasma concentrations of concomitant antiepileptic drugs or alter vital signs or laboratory parameters. No significant difference in the incidence of adverse events was observed between treatment groups (70.8% for the 1,000-mg group and 75.5% for the 2,000-mg group), or between the LEV and placebo groups (73.2% for placebo group). The most commonly reported adverse effects in the LEV group were asthenia, headache, and somnolence.Conclusions: The antiepileptic efficacy and tolerability of LEV (1,000 mg/d and 2,000 mg/d, administered in two divided doses) as add-on therapy was established in patients with refractory partial seizures in this clinical study.

Abstract. Temperate grasslands account for c. 20% of the land area in Europe. Carbon accumulation in grassland ecosystems occurs mostly below ground and changes in soil organic carbon stocks may result from land use changes (e.g. conversion of arable land to grassland) and grassland management. Grasslands also contribute to the biosphere±atmosphere exchange of non-CO 2 radiatively active trace gases, with¯uxes intimately linked to management practices. In this article, we discuss the current knowledge on carbon cycling and carbon sequestration opportunities in temperate grasslands. First, from a simple two-parameter exponential model ®tted to literature data, we assess soil organic carbon¯uxes resulting from land use change (e.g. between arable and grassland) and from grassland management. Second, we discuss carbon¯uxes within the context of farming systems, including crop±grass rotations and farm manure applications. Third, using a grassland ecosystem model (PaSim), we provide estimates of the greenhouse gas balance, in CO 2 equivalents, of pastures for a range of stocking rates and of N fertilizer applications. Finally, we consider carbon sequestration opportunities for France resulting from the restoration of grasslands and from the deintensi®cation of intensive livestock breeding systems. We emphasize major uncertainties concerning the magnitude and non-linearity of soil carbon stock changes in agricultural grasslands as well as the emissions of N 2 O from soil and of CH 4 from grazing livestock.

Enhancement of soil nitrogen (N) cycling by grazing has been observed in many grassland ecosystems. However, whether grazing affects the activity only of the key microbial functional groups driving soil N dynamics or also affects the size (cell number) and/or composition of these groups remains largely unknown. We studied the enzyme activity, size, and composition of five soil microbial communities (total microbial and total bacterial communities, and three functional groups driving N dynamics: nitrifiers, denitrifiers, and free N2 fixers) in grassland sites experiencing contrasting sheep grazing regimes (one light grazing [LG] site and one intensive grazing [IG] site) at two topographical locations. Enzyme activity was determined by potential carbon mineralization, nitrification, denitrification, and N2 fixation assays. The size of each community (except N2 fixers) was measured by the most‐probable‐number technique. The composition of the total soil microbial community was characterized by phospholipid fatty acid analysis (PLFA), and the genetic structure of the total bacterial community was assessed by ribosomal intergenic spacer analysis. The genetic structures of the ammonia‐oxidizing, nitrate‐reducing, and N2‐fixing communities were characterized by polymerase chain reaction and restriction fragment length polymorphism (PCR‐RFLP) or by polymerase chain reaction and denaturing gradient gel electrophoresis (PCR‐DGGE) targeting group‐specific genes. Greater enzyme activities, particularly for nitrification, were observed in IG than in LG sites at both topographical locations. The numbers of heterotrophs, nitrifiers, and denitrifiers were higher in IG than in LG sites at both topographical locations. The amplitude of changes in community size was higher than that of community enzyme activity. Phospholipid and nucleic acid analyses showed that the composition/structure of all the communities, except nitrate reducers, differed between IG and LG sites at both locations. For each community, changes in activity were correlated with changes in the occurrence of a few individual PLFAs or DNA fragments. Our results thus indicate that grazing enhances the activity of soil microbial communities but also concurrently induces changes in the size and composition/structure of these communities on the sites studied. Although the generality of our conclusions should be tested in other systems, these results are of major importance for predicting the effects of future disturbances or changed grazing regimes on the functioning of grazed ecosystems.

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