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

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

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

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

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

Short-Term Neurodevelopmental Outcome in Term Neonates Treated with Phenobarbital versus Levetiracetam: A Single-Center Experience

BACKGROUND: Phenobarbital (PB) has been traditionally used as the first-line treatment for neonatal seizures. More recently, levetiracetam (LEV) has been increasingly used as a promising newer antiepileptic medication for treatment of seizures in neonates. OBJECTIVES: The aim of our study was to compare the effect of PB vs. LEV on short-term neurodevelopmental outcome in infants treated for neonatal seizures. METHOD: This randomized, one-blind prospective study was conducted on term neonates admitted to the Neonatal Intensive Care Unit of S. Bambino Hospital, University Hospital "Policlinico-Vittorio Emanuele," Catania, Italy, from February 2016 to February 2018. Thirty term neonates with seizures were randomized to receive PB or LEV; the Hammersmith Neonatal Neurological Examination (HNNE) was used at baseline (T0) and again one month after the initial treatment (T1). RESULTS: We found a significantly positive HNNE score for the developmental outcomes, specifically tone and posture, in neonates treated with LEV. There was no significant improvement in the HNNE score at T1 in the neonates treated with PB. CONCLUSION: This study suggests a positive effect of levetiracetam on tone and posture in term newborns treated for neonatal seizures. If future randomized-controlled studies also show better efficacy of LEV in the treatment of neonatal seizures, LEV might potentially be considered as the first-line anticonvulsant in this age grou

Leading-edge flow criticality as a governing factor in leading-edge-vortex initiation in unsteady airfoil flows

A leading-edge suction parameter (LESP) that is derived from potential flow theory as a measure of suction at the airfoil leading edge is used to study initiation of leading-edge vortex (LEV) formation in this article. The LESP hypothesis is presented, which states that LEV formation in unsteady flows for specified airfoil shape and Reynolds number occurs at a critical constant value of LESP, regardless of motion kinematics. This hypothesis is tested and validated against a large set of data from CFD and experimental studies of flows with LEV formation. The hypothesis is seen to hold except in cases with slow-rate kinematics which evince significant trailing-edge separation (which refers here to separation leading to reversed flow on the aft portion of the upper surface), thereby establishing the envelope of validity. The implication is that the critical LESP value for an airfoil–Reynolds number combination may be calibrated using CFD or experiment for just one motion and then employed to predict LEV initiation for any other (fast-rate) motion. It is also shown that the LESP concept may be used in an inverse mode to generate motion kinematics that would either prevent LEV formation or trigger the same as per aerodynamic requirements

Petiolate wings: effects on the leading-edge vortex in flapping flight

The wings of many insect species including crane flies and damselflies are petiolate (on stalks), with the wing planform beginning some distance away from the wing hinge, rather than at the hinge. The aerodynamic impact of flapping petiolate wings is relatively unknown, particularly on the formation of the lift-augmenting leading-edge vortex (LEV): a key flow structure exploited by many insects, birds and bats to enhance their lift coefficient. We investigated the aerodynamic implications of petiolation P using particle image velocimetry flow field measurements on an array of rectangular wings of aspect ratio 3 and petiolation values of P = 1–3. The wings were driven using a mechanical device, the ‘Flapperatus’, to produce highly repeatable insect-like kinematics. The wings maintained a constant Reynolds number of 1400 and dimensionless stroke amplitude Λ* (number of chords traversed by the wingtip) of 6.5 across all test cases. Our results showed that for more petiolate wings the LEV is generally larger, stronger in circulation, and covers a greater area of the wing surface, particularly at the mid-span and inboard locations early in the wing stroke cycle. In each case, the LEV was initially arch-like in form with its outboard end terminating in a focus-sink on the wing surface, before transitioning to become continuous with the tip vortex thereafter. In the second half of the wing stroke, more petiolate wings exhibit a more detached LEV, with detachment initiating at approximately 70% and 50% span for P = 1 and 3, respectively. As a consequence, lift coefficients based on the LEV are higher in the first half of the wing stroke for petiolate wings, but more comparable in the second half. Time-averaged LEV lift coefficients show a general rise with petiolation over the range tested.This work was supported by an EPSRC Career Acceleration Fellowship to R.J.B. (EP/H004025/1)

Peroxide impact on the fate of veterinary drugs in fertilizers

The presence of veterinary medicines in organic manure causes soil contamination which contributes to increasing resistance of indigenous microflora to drugs and results in greater susceptibility of people to allergies. The main aim of the study was to assess the efficiency of inorganic peroxide mixtures (PM) with calcium peroxide content (CaO2) in the stabilization process of manure contaminated with antiparasitic agents: albendazole (ALB) and levamisole (LEV). As a solid, CaO2 is relatively stable against decomposition. In contact with water, however, it hydrolyzes with release of oxygen. The hydrolyzation of CaO2 proceeds very slowly in soil, which guarantees the constant release of hydrogen peroxide that subsequently becomes the source of free radicals (chemical oxidation) and oxygen (aerobic conditions for the microbes). It may contribute to continuous elimination of drugs from manure. The study has demonstrated that there were significant differences in ALB and LEV conversion stimulated by the PM addition. PM supplementation increased the drug availability (on average 15% and 25% increase in the initial concentration for ALB and for LEV, respectively), thereby increasing the initial rate of reaction. Elimination of ALB and LEV from the manure sorption complex is followed by Ca2+ saturation. The initial degradation rate was affected by PM for both drugs, but the mechanisms of decomposition have been modified only for ALB. The loss of ALB in the peroxide supplemented samples was 92%, and in the samples, without the PM, it did not exceed 61%. Loss of LEV was over 90% irrespective of PM supplementation.Web of Science74132231