Safety profile of oxcarbazepine: results from a prescription-event monitoring study

Purpose: To monitor safety of oxcarbazepine, prescribed in primary care in England, using prescription-event monitoring (PEM). Methods: Postmarketing surveillance using observational cohort technique of PEM. Exposure data were obtained from dispensed British National Health Service prescriptions issued by general practitioners (GPs) March 2000–July 2003. Demographic, drug utilization, and clinical event data were collected from questionnaires posted to GPs at least 6 months after first prescription date for each patient. Incidence densities (IDs) (number of first reports per 1,000 patient-months of treatment) were calculated and differences for events reported in month 1 (ID1) and months 2–6 (ID2–6) (99% confidence intervals) were examined for changes in event rates. Follow-up and causality assessment of medically significant events were undertaken. Results: The cohort comprised 2,243 patients [mean age 40.4 years; range 2–99 years; standard deviation (SD) 18.8; 46.3% (n = 1,038) male]. Most frequently reported primary indications were epilepsy, convulsion (n = 1,111; 49.5%, n = 209; 9.3%, respectively). GPs recorded 932 reasons for stopping medication in 698 (31.1%) patients; most frequent clinical reason “drowsiness/sedation” (n = 57; 2.5% of cohort). Clinical events (excluding indication) associated with starting treatment (lower 99% CI > 0) included: “drowsiness/sedation” (ID1-ID2–6 = 14.2), “nausea/vomiting” (ID1-ID2–6 = 13.0), and dizziness (ID1-ID2–6 = 11.6). Events followed up and assessed as probably related to oxcarbazepine use included rash (7 of 11) and hyponatremia (15 of 38). Discussion:  There were no serious adverse drug reactions reported during this study. Results of the study should be taken in context with other epidemiologic studies

Spectral scaling of the Leray-α\alpha model for two-dimensional turbulence

We present data from high-resolution numerical simulations of the Navier-Stokes-$\alpha$ and the Leray-$\alpha$ models for two-dimensional turbulence. It was shown previously (Lunasin et al., J. Turbulence, 8, (2007), 751-778), that for wavenumbers $k$ such that $k\alpha\gg 1$, the energy spectrum of the smoothed velocity field for the two-dimensional Navier-Stokes-$\alpha$ (NS-$\alpha$) model scales as $k^{-7}$. This result is in agreement with the scaling deduced by dimensional analysis of the flux of the conserved enstrophy using its characteristic time scale. We therefore hypothesize that the spectral scaling of any $\alpha$-model in the sub-$\alpha$ spatial scales must depend only on the characteristic time scale and dynamics of the dominant cascading quantity in that regime of scales. The data presented here, from simulations of the two-dimensional Leray-$\alpha$ model, confirm our hypothesis. We show that for $k\alpha\gg 1$, the energy spectrum for the two-dimensional Leray-$\alpha$ scales as $k^{-5}$, as expected by the characteristic time scale for the flux of the conserved enstrophy of the Leray-$\alpha$ model. These results lead to our conclusion that the dominant directly cascading quantity of the model equations must determine the scaling of the energy spectrum.Comment: 11 pages, 4 figure

Analytical Study of Certain Magnetohydrodynamic-alpha Models

In this paper we present an analytical study of a subgrid scale turbulence model of the three-dimensional magnetohydrodynamic (MHD) equations, inspired by the Navier-Stokes-alpha (also known as the viscous Camassa-Holm equations or the Lagrangian-averaged Navier-Stokes-alpha model). Specifically, we show the global well-posedness and regularity of solutions of a certain MHD-alpha model (which is a particular case of the Lagrangian averaged magnetohydrodynamic-alpha model without enhancing the dissipation for the magnetic field). We also introduce other subgrid scale turbulence models, inspired by the Leray-alpha and the modified Leray-alpha models of turbulence. Finally, we discuss the relation of the MHD-alpha model to the MHD equations by proving a convergence theorem, that is, as the length scale alpha tends to zero, a subsequence of solutions of the MHD-alpha equations converges to a certain solution (a Leray-Hopf solution) of the three-dimensional MHD equations.Comment: 26 pages, no figures, will appear in Journal of Math Physics; corrected typos, updated reference

Mechanistic mathematical model of polarity in yeast

The establishment of cell polarity involves positive-feedback mechanisms that concentrate polarity regulators, including the conserved GTPase Cdc42p, at the “front” of the polarized cell. Previous studies in yeast suggested the presence of two parallel positive-feedback loops, one operating as a diffusion-based system, and the other involving actin-directed trafficking of Cdc42p on vesicles. F-actin (and hence directed vesicle traffic) speeds fluorescence recovery of Cdc42p after photobleaching, suggesting that vesicle traffic of Cdc42p contributes to polarization. We present a mathematical modeling framework that combines previously developed mechanistic reaction-diffusion and vesicle-trafficking models. Surprisingly, the combined model recapitulated the observed effect of vesicle traffic on Cdc42p dynamics even when the vesicles did not carry significant amounts of Cdc42p. Vesicle traffic reduced the concentration of Cdc42p at the front, so that fluorescence recovery mediated by Cdc42p flux from the cytoplasm took less time to replenish the bleached pool. Simulations in which Cdc42p was concentrated into vesicles or depleted from vesicles yielded almost identical predictions, because Cdc42p flux from the cytoplasm was dominant. These findings indicate that vesicle-mediated delivery of Cdc42p is not required to explain the observed Cdc42p dynamics, and raise the question of whether such Cdc42p traffic actually contributes to polarity establishment

Real-time lattice boltzmann shallow waters method for breaking wave simulations

We present a new approach for the simulation of surfacebased fluids based in a hybrid formulation of Lattice Boltzmann Method for Shallow Waters and particle systems. The modified LBM can handle arbitrary underlying terrain conditions and arbitrary fluid depth. It also introduces a novel method for tracking dry-wet regions and moving boundaries. Dynamic rigid bodies are also included in our simulations using a two-way coupling. Certain features of the simulation that the LBM can not handle because of its heightfield nature, as breaking waves, are detected and automatically turned into splash particles. Here we use a ballistic particle system, but our hybrid method can handle more complex systems as SPH. Both the LBM and particle systems are implemented in CUDA, although dynamic rigid bodies are simulated in CPU. We show the effectiveness of our method with various examples which achieve real-time on consumer-level hardware.Peer ReviewedPostprint (author's final draft

Time evolution, cyclic solutions and geometric phases for general spin in an arbitrarily varying magnetic field

A neutral particle with general spin and magnetic moment moving in an arbitrarily varying magnetic field is studied. The time evolution operator for the Schr\"odinger equation can be obtained if one can find a unit vector that satisfies the equation obeyed by the mean of the spin operator. There exist at least $2s+1$ cyclic solutions in any time interval. Some particular time interval may exist in which all solutions are cyclic. The nonadiabatic geometric phase for cyclic solutions generally contains extra terms in addition to the familiar one that is proportional to the solid angle subtended by the closed trace of the spin vector.Comment: revtex4, 8 pages, no figur

Time evolution, cyclic solutions and geometric phases for the generalized time-dependent harmonic oscillator

The generalized time-dependent harmonic oscillator is studied. Though several approaches to the solution of this model have been available, yet a new approach is presented here, which is very suitable for the study of cyclic solutions and geometric phases. In this approach, finding the time evolution operator for the Schr\"odinger equation is reduced to solving an ordinary differential equation for a c-number vector which moves on a hyperboloid in a three-dimensional space. Cyclic solutions do not exist for all time intervals. A necessary and sufficient condition for the existence of cyclic solutions is given. There may exist some particular time interval in which all solutions with definite parity, or even all solutions, are cyclic. Criterions for the appearance of such cases are given. The known relation that the nonadiabatic geometric phase for a cyclic solution is proportional to the classical Hannay angle is reestablished. However, this is valid only for special cyclic solutions. For more general ones, the nonadiabatic geometric phase may contain an extra term. Several cases with relatively simple Hamiltonians are solved and discussed in detail. Cyclic solutions exist in most cases. The pattern of the motion, say, finite or infinite, can not be simply determined by the nature of the Hamiltonian (elliptic or hyperbolic, etc.). For a Hamiltonian with a definite nature, the motion can changes from one pattern to another, that is, some kind of phase transition may occur, if some parameter in the Hamiltonian goes through some critical value.Comment: revtex4, 28 pages, no figur

Two-photon fluorescence imaging of intracellular hydrogen peroxide with chemoselective fluorescent probes

Abstract. We present the application of two-photon fluorescence (TPF) imaging to monitor intracellular hydrogen peroxide (H2O2) production in brain cells. For selective imaging of H2O2 over other reactive oxygen species, we employed small-molecule fluorescent probes that utilize a chemoselective boronate deprotection mechanism. Peroxyfluor-6 acetoxymethyl ester detects global cellular H2O2 and mitochondria peroxy yellow 1 detects mitochondrial H2O2. Two-photon absorption cross sections for these H2O2 probes are measured with a mode-locked Ti:sapphire laser in the wavelength range of 720 to 1040 nm. TPF imaging is demonstrated in the HT22 cell line to monitor both cytoplasmic H2O2 and localized H2O2 production in mitochondria. Endogenous cytoplasmic H2O2 production is detected with TPF imaging in rat astrocytes modified with d-amino acid oxidase. The TPF H2O2 imaging demonstrated that these chemoselective probes are powerful tools for the detection of intracellular H2O2

The fate of steroid estrogens: Partitioning during wastewater treatment and onto river sediments

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Springer Science+Business Media B.V.The partitioning of steroid estrogens in wastewater treatment and receiving waters is likely to influence their discharge to, and persistence in, the environment. This study investigated the partitioning behaviour of steroid estrogens in both laboratory and field studies. Partitioning onto activated sludge from laboratory-scale Husmann units was rapid with equilibrium achieved after 1 h. Sorption isotherms and Kd values decreased in the order 17α-ethinyl estradiol > 17α-estradiol > estrone > estriol without a sorption limit being achieved (1/n >1). Samples from a wastewater treatment works indicated no accumulation of steroid estrogens in solids from primary or secondary biological treatment, however, a range of steroid estrogens were identified in sediment samples from the River Thames. This would indicate that partitioning in the environment may play a role in the long-term fate of estrogens, with an indication that they will be recalcitrant in anaerobic conditions.EPSR