Levetiracetam in clinical practice: efficacy and tolerability in epilepsy.

BACKGROUND: The aim of this study was to evaluate efficacy and tolerability of levetiracetam (LEV) in patients with different epilepsy syndromes. METHODS: We evaluated epileptic patients seen in the previous 18 months, including all patients with present or past exposure to LEV. Tolerability of LEV therapy was evaluated in all patients; efficacy was evaluated only in patients who had received LEV for at least six months. Two hundred and two patients were included in the study. Patients were considered responsive when showing a > 50% reduction in seizures frequency and non-responders when seizure frequency was unchanged, worsened or showed a reduction < 50%. RESULTS: Thirty patients did not complete six months of LEV treatment and dropped out. 57.4% of the patients with uncontrolled seizures treated for at least six months were responders, with 27.7% seizure free. Adverse effects were observed in 46 patients (23%) and were responsible for early drop out in 26. Adverse effects occurred significantly more often in females than in males (30.6% vs 13.2%); moreover, nearly 30% of women with adverse effects complained of more than one adverse effect, while this was never observed in male patients. CONCLUSIONS: Our study shows LEV as a well tolerated and effective treatment, both in monotherapy and as an add-on. Further investigations on larges samples are needed to investigate the issue of gender-related tolerability

Rotational accelerations stabilize leading edge vortices on revolving fly wings

The aerodynamic performance of hovering insects is largely explained by the presence of a stably attached leading edge vortex (LEV) on top of their wings. Although LEVs have been visualized on real, physically modeled, and simulated insects, the physical mechanisms responsible for their stability are poorly understood. To gain fundamental insight into LEV stability on flapping fly wings we expressed the Navier–Stokes equations in a rotating frame of reference attached to the wing's surface. Using these equations we show that LEV dynamics on flapping wings are governed by three terms: angular, centripetal and Coriolis acceleration. Our analysis for hovering conditions shows that angular acceleration is proportional to the inverse of dimensionless stroke amplitude, whereas Coriolis and centripetal acceleration are proportional to the inverse of the Rossby number. Using a dynamically scaled robot model of a flapping fruit fly wing to systematically vary these dimensionless numbers, we determined which of the three accelerations mediate LEV stability. Our force measurements and flow visualizations indicate that the LEV is stabilized by the `quasi-steady' centripetal and Coriolis accelerations that are present at low Rossby number and result from the propeller-like sweep of the wing. In contrast, the unsteady angular acceleration that results from the back and forth motion of a flapping wing does not appear to play a role in the stable attachment of the LEV. Angular acceleration is, however, critical for LEV integrity as we found it can mediate LEV spiral bursting, a high Reynolds number effect. Our analysis and experiments further suggest that the mechanism responsible for LEV stability is not dependent on Reynolds number, at least over the range most relevant for insect flight (100<Re<14,000). LEVs are stable and continue to augment force even when they burst. These and similar findings for propellers and wind turbines at much higher Reynolds numbers suggest that even large flying animals could potentially exploit LEV-based force augmentation during slow hovering flight, take-offs or landing. We calculated the Rossby number from single-wing aspect ratios of over 300 insects, birds, bats, autorotating seeds, and pectoral fins of fish. We found that, on average, wings and fins have a Rossby number close to that of flies (Ro=3). Theoretically, many of these animals should therefore be able to generate a stable LEV, a prediction that is supported by recent findings for several insects, one bat, one bird and one fish. This suggests that force augmentation through stably attached (leading edge) vortices could represent a convergent solution for the generation of high fluid forces over a quite large range in size

Efficacy and tolerability of adjunctive brivaracetam in patients with prior antiepileptic drug exposure: A post-hoc study.

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV at enrollment were excluded from this analysis. Patients were categorized by their status of prior exposure to LEV, carbamazepine (CBZ), topiramate (TPM), or lamotrigine (LTG), to investigate any consistent trend towards reduced response in AED-exposed subgroups compared to AED-naïve subgroups, regardless of the mechanism of action. Study completion rates, percent reduction from baseline in focal seizure frequency over placebo, ≥50% responder rates, and tolerability were evaluated for each subgroup. A total of 1160 patients were investigated. Study completion rates were similar in the AED-exposed subgroups and AED-naïve subgroups. In subgroups with (531 patients) or without (629 patients) prior LEV exposure, ≥50% responder rates for each dose of BRV compared with placebo were generally higher among the LEV-naïve subgroups than the previously LEV-exposed subgroups. LEV-exposed subgroups receiving BRV doses ≥50mg/day showed greater ≥50% responder rates than those receiving placebo. Similar results were observed for CBZ, TPM, and LTG. Previous treatment failure with commonly prescribed AEDs (LEV, CBZ, TPM, or LTG) is associated with a reduced response to BRV irrespective of the mechanism of action. Hence, this post-hoc analysis indicates that previous treatment failure with LEV does not preclude the use of BRV in patients with epilepsy

High level of treatment failure with commonly used anthelmintics on Irish sheep farms

peer-reviewedBackground: In 2013 a Technology Adoption Program for sheep farmers was established to encourage the implementation of best management practices on sheep farms in Ireland. There were 4,500 participants in this programme in 2013. As part of this programme, farmers had the option to carry out a drench test to establish the efficacy of their anthelmintic treatment. Results: Flock faecal samples were collected before and after treatment administration and gastrointestinal nematode eggs enumerated. In total there were 1,893 participants in the task, however only 1,585 included both a pre- and post-treatment faecal sample. Of those, 1,308 provided information on the anthelmintic product that they used with 46%, 23% and 28% using a benzimidazole (BZ), levamisole (LEV) and macrocyclic lactone (ML) product respectively. The remaining farmers used a product inapplicable for inclusion in the task such as a flukicide or BZ/LEV combination product. Samples were included for analysis of drench efficacy if the pre-treatment flock egg count was ≥200 eggs per gram and the interval post-sampling was 10–14 days for BZ products, 4–7 days for LEV products and 14–18 days for ML products. These criteria reduced the number of valid tests to 369, 19.5% of all tests conducted. If the reduction post-treatment was ≥95% the treatment was considered effective. Only 51% of treatments were considered effective using this criterion. There was a significant difference in efficacy between the anthelmintic drug classes with BZ effective in only 30% of treatments, LEV effective in 52% of cases and ML effective in 76% of cases. Conclusions: Gastrointestinal nematode anthelmintic treatments, as practiced on Irish farms, have a high failure rate. There was a significant difference between the efficacies of the anthelmintic classes with BZ the least effective and ML the most effective

The moduli space of (1,11)-polarized abelian surfaces is unirational

We prove that the moduli space A_{11}^{lev} of (1,11) polarized abelian surfaces with level structure of canonical type is birational to Klein's cubic hypersurface: a^2b+b^2c+c^2d+d^2e+e^2a=0 in P^4. Therefore, A_{11}^{lev} is unirational but not rational, and there are no Gamma_{11}-cusp forms of weight 3. The same methods also provide an easy proof of the rationality of A_{9}^{lev}.Comment: 27 pages, TeX with diagrams.tex. Related Macaulay2 code and PostScript file available at http://www.math.columbia.edu/~psorin

A Hierarchy of Maps Between Compacta

Let CH be the class of compacta (i.e., compact Hausdorff spaces), with BS the subclass of Boolean spaces. For each ordinal α and pair $\langle K,L\rangle$ of subclasses of CH, we define Lev≥α K,L), the class of maps of level at least α from spaces in K to spaces in L, in such a way that, for finite α, Lev≥α (BS,BS) consists of the Stone duals of Boolean lattice embeddings that preserve all prenex first-order formulas of quantifier rank α. Maps of level ≥ 0 are just the continuous surjections, and the maps of level ≥ 1 are the co-existential maps introduced in [8]. Co-elementary maps are of level ≥α for all ordinals α; of course in the Boolean context, the co-elementary maps coincide with the maps of level ≥ω. The results of this paper include: (i) every map of level ≥ω is co-elementary; (ii) the limit maps of an ω-indexed inverse system of maps of level ≥α are also of level ≥α; and (iii) if K is a co-elementary class, k \u3c ω and Lev≥ k(K,K) = Lev≥ k+1 (K,K), then Lev≥ k(K,K) = Lev≥ω(K,K). A space X ∈ K is co-existentially closed in K if Lev≥ 0(K, X) = Lev≥ 1 (K, X). Adapting the technique of adding roots, by which one builds algebraically closed extensions of fields (and, more generally, existentially closed extensions of models of universal-existential theories), we showed in [8] that every infinite member of a co-inductive co-elementary class (such as CH itself, BS, or the class CON of continua) is a continuous image of a space of the same weight that is co-existentially closed in that class. We show here that every compactum that is co-existentially closed in CON (a co-existentially closed continuum) is both indecomposable and of covering dimension on

Towards the C^0 flux conjecture

In this note, we generalise a result of Lalonde, McDuff and Polterovich concerning the $C^0$ flux conjecture, thus confirming the conjecture in new cases of a symplectic manifold. Also, we prove the continuity of the flux homomorphism on the space of smooth symplectic isotopies endowed with the $C^0$ topology, which implies the $C^0$ rigidity of Hamiltonian paths, conjectured by Seyfaddini