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

Low bit rate speech transmission: classified vector excitation coding

Vector excitation coding (VXC) is a speech digitisation technique growing in popularity. Problems associated with VXC systems are high computational complexity and poor reconstruction of plosives. The Pairwise Nearest Neighbour (PNN) clustering algorithm is proposed as an efficient method of codebook design. It is demonstrated to preserve plosives better than the Linde-Buzo-Gary (LBG) algorithm [34] and maintain similar quality to LBG for other speech Classification of the residual is then studied. This reduces codebook search complexity and enables a shortcut in computation of the PNN algorithm to be exploited

Influence of Protein Concentration on Heat-Induced Aggregation and Subsequent Functionality of Whey Proteins

The usage of whey proteins as a source of nutrition in foods and beverages is ever increasing, creating a demand for highly concentrated and functional forms of protein. Their use as an ingredient to increase protein content in foods is growing, and the ability to withstand thermal treatment while concentrated is paramount to reducing process instability, e.g., high viscosity, precipitation and/or fouling of heat exchangers. The objective of this thesis was to investigate the effect of protein concentration on the heat-induced aggregation of whey proteins and subsequent increases in viscosity in dispersed and emulsified systems. Increasing the protein content of whey solutions from 1 to 12% (w/w) was accompanied by a reduction in denaturation temperature and increase in both viscosity and the shear rate at which onset of turbulent flow was observed. On heating to 85 °C for 30 s, the particle size (Dynamic light scattering, DLS) of aggregates was significantly (P < 0.05) affected by both protein concentration (1 to 12 % w/w) and pH (6.2, 6.7 and 7.2). Aggregates of ~ 50 nm were formed at higher pH (7.2) and protein concentration (12%), contributing to greater heat stability upon subsequent heating compared to aggregates of ~ 100 nm formed from the heat-treatment of 1% whey at pH 6.2. In an emulsified system, simulating that of a 1st stage infant formula, increasing the ratio of α-lactalbumin to β-lactoglobulin significantly (P < 0.05) reduced the level of large soluble aggregates formed on heating, improved emulsion stability and reduced apparent viscosity during concentration. Differences in these physicochemical properties are attributed to underlying molecular changes in the mechanism(s) of aggregation due to a reduction in the total number free thiol groups in the system as β-lactoglobulin is replaced by α-lactalbumin. To better understand the complex interactions involving β-lactoglobulin, 1H13C HSQC solution NMR (Nuclear Magnetic Resonance [13C,1H]–Heteronuclear Single Quantum Correlated spectroscopy) and Fourier Transform Infrared (FTIR) spectroscopy were used to observe molecular rearrangement at low (1% (w/w)) and high concentration (12% (w/w)) at either 62 or 85 °C. FTIR showed that there was formation of antiparallel inter-bonded β-sheets in both 1 and 12% samples heat-treated at 85 °C for 10 minutes, indicating protein denaturation and subsequent aggregation. Partial reversible denaturation was observed by NMR after heat-treatment at 62 °C; however, at 85 °C, denaturation and the subsequent aggregation of β-lactoglobulin monomers was extensive. Results suggest that although β-lactoglobulin monomers and dimers are denatured, the aggregates formed are comprised of unfolded β-lactoglobulin monomers that behaved “native-like”. This thesis demonstrates that by controlling the extent and size of aggregates through reduction in β-lactoglobulin and soluble ‘seed’ aggregates, it is possible to modulate viscosity in concentrated whey protein dispersions and emulsified systems

Evaluating the Performance of Vulkan GLSL Compute Shaders in Real-Time Ray-Traced Audio Propagation Through 3D Virtual Environments

Real time ray tracing is a growing area of interest with applications in audio processing. However, real time audio processing comes with strict performance requirements, which parallel computing is often used to overcome. As graphics processing units (GPUs) have become more powerful and programmable, general-purpose computing on graphics processing units (GPGPU) has allowed GPUs to become extremely powerful parallel processors, leading them to become more prevalent in the domain of audio processing through platforms such as CUDA. The aim of this research was to investigate the potential of GLSL compute shaders in the domain of real time audio processing. Specifically regarding real time ray tracing tasks. To do this a number of GLSL compute shaders were created, along with a C++ Vulkan application with which to execute them. These shaders facilitate the propagation of audio, using ray tracing, through a virtual environment, and implement 3D space partitioning and ray intersection prediction in order to gauge the effectiveness of these optimisations for this task. Statistically significant results show that the GLSL compute shaders successfully propagated audio through a virtual environment, returning results to the host system in real time, within 30 milliseconds. However, while this capability was shown, significantly detailed virtual environments prevented results from being returned in real time. Indicating a potential for future research and optimisation

The Synthesis of Glucosamine-Based Derivatives with Potential as Immunomodulators, Kinase Inhibitors, and Prodrugs

Chapter 1 gives a brief outline of the relevance of carbohydrates in biological systems. Special attention has been given to the roles of glucosamine and N-acetyl glucosamine. Chapter 2 details the synthesis of novel glucosamine-based serine glycolipids, which were tested for their immunomodulatory ability. The experimental conditions investigated are discussed in detail. Chapter 3 describes the synthesis of a glucosamine-based serine building block, and its incorporation into a series of glycopeptides, via SPPS techniques, with potential as a kinase inhibitor. The experimental conditions for the synthesis and purification of these peptides are discussed in detail. Chapter 4 describes an investigation into the introduction of functionalities at the C-6 position of the sugar moiety, with the aim of synthesising an azido-functionalised glucosamine derivative. The experimental details of this investigation are described. Chapter 5 describes the synthesis of a glucosamine-based dopamine derivative, which has potential as a dopamine prodrug. The various approaches taken in this synthesis, and the experimental conditions are discussed in detail. Chapter 6 gives the experimental details and characterisations for the compounds reported throughout this thesis. Chapter 7 contains appendices describing 1H NMR assignation, and also experimental details of attempted experiments. Chapter 8 contains the bibliographic information used as references in this thesis

Determination of long-term spatial and seasonal distribution of contaminants in an urban river and estuarine system using polarographic techniques

The Tolka River and Estuary, Co. Dublin, Ireland, is a typical Irish urban river and estuarine system. It has significant metal and organometal contaminant loading. A one-month rapid sampling and analysis regime was devised to optimise riverine and estuarine sampling techniques and to determine seasonality of contaminant distribution. Over a thirty-month period contaminant concentrations within the surface sediment of the aquatic system were analysed from twenty sampling points. Six metals (Cd, Cr, Cu, Ni, Pb and Zn) and an organometal (TBT) were analysed using Differential Pulse Polarography for thirty and nineteen months respectively. Organic Matter, Suspended Particulate Matter, pH, Salinity and metal content of the water column were also analysed. This thirty-month assessment created an extensive database to determine spatial and seasonal distributions of contaminants over time and various in situ environmental and anthropogenic parameters that influence these distributions. It was found that contaminant concentrations within surface sediment are highly variable over a twelve-month period and that environmental conditions and anthropogenic sources of contaminants are the key factors affecting spatial and seasonal distributions