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

Development and evaluation of a novel orally administered subunit vaccine to control foodborne pathogens

Development of vaccines for effective control of foodborne pathogens and infection represents an important development in reducing public health risk. Advancements in the area of biotechnology have increased innovative potential and allow new technologies to be used as a promising control strategy for alternatives to antibiotics. We have been working to create a novel vaccine platform that incorporates a subunit/epitope sequence, common for all E. coli strains (broad spectrum), into an inactivated orally administered vaccine platform that protects against infection and disease by inducing mucosal immunity

The Human Experiment in Treatment: A Means to the End of Offender Recidivism

This chapter highlights the role that high-quality evaluations, especially randomized experiments, and rigorous techniques of research synthesis (which include high-quality evaluations) have played in recent years in drawing attention to the importance and effectiveness of correctional treatment for offenders as well as the ineffectiveness of many popular “get tough” programs

Identification of cardiotoxicity related to non-small cell lung cancer (NSCLC) treatments: A systematic review

Introduction In the last few decades, there has been a rapid development in cancer therapies and improved detection strategies, hence the death rates caused by cancer have decreased. However, it has been reported that cardiovascular disease has become the second leading cause of long-term morbidity and fatality among cancer survivors. Cardiotoxicity from anticancer drugs affects the heart’s function and structure and can occur during any stage of the cancer treatments, which leads to the development of cardiovascular disease. Objectives To investigate the association between anticancer drugs for non-small cell lung cancer (NSCLC) and cardiotoxicity as to whether: different classes of anticancer drugs demonstrate different cardiotoxicity potentials; different dosages of the same drug in initial treatment affect the degree of cardiotoxicity; and accumulated dosage and/or duration of treatments affect the degree of cardiotoxicity Methods This systematic review included studies involving patients over 18 years old with NSCLC and excluded studies in which patients’ treatments involve radiotherapy only. Electronic databases and registers including Cochrane Library, National Cancer Institute (NCI) Database, PubMed, Scopus, Web of Science, ClinicalTrials.gov and the European Union Clinical Trials Register were systematically searched from the earliest available date up until November 2020. A full version protocol of this systematic review (CRD42020191760) had been published on PROSPERO. Results A total of 1785 records were identified using specific search terms through the databases and registers; 74 eligible studies were included for data extraction. Based on data extracted from the included studies, anticancer drugs for NSCLC that are associated with cardiovascular events include bevacizumab, carboplatin, cisplatin, crizotinib, docetaxel, erlotinib, gemcitabine and paclitaxel. Hypertension was the most reported cardiotoxicity as 30 studies documented this cardiovascular adverse event. Other reported treatment-related cardiotoxicities include arrhythmias, atrial fibrillation, bradycardia, cardiac arrest, cardiac failure, coronary artery disease, heart failure, ischemia, left ventricular dysfunction, myocardial infarction, palpitations, and tachycardia. Conclusion The findings of this systematic review have provided a better understanding of the possible association between cardiotoxicities and anticancer drugs for NSCLC. Whilst variation is observed across different drug classes, the lack of information available on cardiac monitoring can result in underestimation of this association. Systematic Review Registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191760, identifier PROSPERO CRD42020191760

An Improved Method of Documenting Activity Patterns of Post-Emergence Polar Bears (Ursus maritimus) in Northern Alaska

Throughout their circumpolar range, pregnant female polar bears (Ursus maritimus) create snow dens in which they give birth to altricial cubs. Because polar bear neonates are born in such an undeveloped state, their survival requires a long, undisturbed period of in-den development. To mitigate human impacts on denning bears, it is necessary to understand the chronology of denning, the behaviors of denning bears, and their sensitivity to human activities. Since 2002, we have studied the den emergence behaviors of polar bears in northern Alaska; however, we moved from using on-site observers (2002 – 03) to using autonomous video systems (2005 – 08). Here we compare the duration, activity budgets, and behaviors of polar bears to see whether observation methods affected their activities. Camera systems recorded nearly 10 times the data per den recorded by human observers (526 h/den and 57 h/den respectively). We found no difference between the two study periods in emergence dates, duration at den sites, abandonment dates, or activity budgets for polar bears. We observed a 16-fold reduction in the number of bear-human interactions when using cameras instead of human observers. There was, however, a marked increase in the intensity of response when using cameras (125 m) as compared to observers in blinds (400 m). An understanding of these activity patterns can be used to manage human activities near dens so as to minimize disturbance.À l’échelle de leur aire de répartition circumpolaire, les ourses polaires (Ursus maritimus) en gestation se créent une tanière de neige pour donner naissance à leurs oursons à développement tardif. Puisque les nouveau-nés de l’ourse polaire naissent dans un état si peu développé, leur survie nécessite une longue période de développement non perturbé en tanière. Afin d’atténuer les incidences de l’être humain sur les ours en tanière, il est nécessaire de comprendre la chronologie de la mise bas, les comportements des ours en tanière et leur sensibilité à l’activité humaine. À partir de 2002, nous avons étudié les comportements de sortie des tanières des ours polaires du nord de l’Alaska, tout d’abord au moyen d’observations faites sur place (en 2002 et 2003) et ensuite, au moyen de caméras vidéo autonomes (de 2005 à 2008). Ici, nous comparons la durée, la répartition des activités et les comportements des ours polaires afin de déterminer si les méthodes d’observation ont influencé leurs activités. Les caméras ont enregistré près de dix fois plus de données par tanière que les observateurs humains (526 h/tanière et 57 h/tanière respectivement). Nous n’avons trouvé aucune différence entre les deux périodes à l’étude en ce qui a trait aux dates de sortie, aux durées de séjour en tanière, aux dates d’abandon ou à la répartition des activités des ours polaires. Lorsque nous avons utilisé des caméras par opposition à des observateurs, nous avons dénoté 16 fois moins d’interactions entre les ours et l’être humain. Cependant, nous avons remarqué une augmentation accrue sur le plan de l’intensité de la réponse lorsque nous nous sommes servis de caméras (125 m) comparativement aux observateurs dissimulés (400 m). La compréhension de ces modèles d’activités peut servir à gérer l’activité humaine à proximité des tanières afin de minimiser les perturbations

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

Development of integrated management practices for the control of Chinese tallow (Triadica sebifera)

Chinese tallow (Triadica sebifera) tree is an aggressive, fast growing, highly adaptable invasive tree of the southeastern United States coastal region. Our study is located on Parris Island Marine Corps Recruit Depot (MCRD) in Beaufort County, South Carolina. Parris Island MCRD. Chinese tallow has been managed on Parris Island MCRD since 2001through the use of herbicides primarily with ‘hack and squirt’ methodology. In 2010, invasive species presence and abundance on Parris Island MCRD was surveyed in order to monitor the Chinese tallow population and to assess the effectiveness of previous control efforts. Results from this survey suggest there is a need for a more effective management approach because the Chinese tallow population in some areas had increased despite herbicide applications. In this study, we seek to find an effective approach for managing Chinese tallow while, at the same time, promoting native species diversity and restoring the forest ecosystem. We will test several integrated treatments including mechanical, herbicide and fire to determine their efficacy on Chinese tallow control as well as their potential adverse effects on native vegetation. The goal of the study is to determine the most effective integrated treatment of Chinese tallow