SUMMARYPurpose: To study the efficacy and safety of eslicarbazepine acetate (ESL) as adjunctive therapy for refractory partial seizures in adults with ‡4 partial-onset seizures (simple or complex, with or without secondary generalization) per 4 weeks despite treatment with 1-2 antiepileptic drugs (AEDs). Methods: This multicenter, parallel-group study had an 8-week, single-blind, placebo baseline phase, after which patients were randomized to placebo (n = 102) or once-daily ESL 400 mg (n = 100), 800 mg (n = 98), or 1,200 mg (n = 102) in the double-blind treatment phase. ESL starting dose was 400 mg; thereafter, ESL was titrated at weekly 400-mg steps to the full maintenance dose (12 weeks). Results: Seizure frequency adjusted per 4 weeks over the maintenance period (primary endpoint) was significantly lower than placebo in the ESL 1,200-mg (p = 0.0003) and 800-mg (p = 0.0028) groups [analysis of covariance (ANCOVA) of logtransformed seizure frequency]. Responder rate was 20% (placebo), 23% (400 mg), 34% (800 mg), and 43% (1,200 mg). Median relative reduction in seizure frequency was 16% (placebo), 26% (400 mg), 36% (800 mg), and 45% (1,200 mg). The most frequent concomitant AEDs were carbamazepine (56-62% of patients), lamotrigine (25-27%), and valproic acid (22-28%). Similar efficacy results were obtained in patients administered ESL with or without carbamazepine as concomitant AED. Discontinuation rates caused by adverse events (AEs) were 3.9% (placebo), 4% (400 mg), 8.2% (800 mg), and 19.6% (1,200 mg). AEs in >10% of any group were dizziness, headache, and diplopia. Most AEs were mild or moderate. Discussion: ESL, 800 and 1,200 mg once-daily, was well tolerated and more effective than placebo in patients who were refractory to treatment with one or two concomitant AEDs.

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Experimental evidence suggests that we live in a spatially flat, accelerating universe composed of roughly one-third of matter (baryonic + dark) and two-thirds of a negative-pressure dark component, generically called dark energy. The presence of such energy not only explains the observed accelerating expansion of the Universe but also provides the remaining piece of information connecting the inflationary flatness prediction with astronomical observations. However, despite of its good observational indications, the nature of the dark energy still remains an open question. In this paper we explore a geometrical explanation for such a component within the context of brane-world theory without mirror symmetry, leading to a geometrical interpretation for dark energy as warp in the universe given by the extrinsic curvature. In particular, we study the phenomenological implications of the extrinsic curvature of a Friedman-Robertson-Walker universe in a five-dimensional constant curvature bulk, with signatures (4,1) or (3,2), as compared with the X-matter (XCDM) model. From the analysis of the geometrically modified Friedman's equations, the deceleration parameter and the Weak Energy Condition, we find a consistent agreement with the presently known observational data on inflation for the deSitter bulk, but not for the anti-deSitter case.

A nonsingular cosmological scenario based on a new phenomenological decay law for the effective A term is proposed. In such a model, the cosmic history began from an instability of the de Sitter spacetime rather than a singularity. The process is characterized by an arbitrary time scale H;' giving the largest value of the cosmological constant (AI=3H,?) and the initial temperature of the Universe. Subsequently, the Universe evolved continuously toward a slightly modified Friedmann-Robertson-Walker cosmology. Among the "remnants" of the primordial inflationary period are the present values of the cosmological term Ao-3PH& the density parameter no-1-P, and the deceleration parameter q o -(