Optimisation of antibiotic therapy in cystic fibrosis patients. Pharmacokinetic considerations

Antibiotic therapy plays a central role in the medical management of patients with cystic fibrosis. While totally convincing efficacy data are lacking, antibiotics probably have a pronounced beneficial effect on both morbidity and mortality. Much has been learned in the past 20 years about antibiotic use in this population. At the same time, new antimicrobial agents with the potential to treat this condition have become available for use. The pharmacokinetics of a number of antibiotic classes, including beta-lactams, aminoglycosides and quinolones, are altered in this patient population. Increased total body clearance is a common occurrence but is not always changed enough to warrant altered dosages. Nonetheless, in light of altered pharmacokinetics in the cystic fibrosis population, appropriate dosage and monitoring parameters for a number of antibiotics have been determined.     

Occurrence of Lawn Care and Agricultural Pesticides in the Don River and Humber River Watersheds (1998–2002)

Between 1998 and 2002, surface water samples were collected from several sites in the Don River and Humber River watersheds, both tributaries to Lake Ontario, and analyzed for a variety of pesticides, including those used for urban lawn care. Analyses included 152 pesticide active ingredients and eight metabolites. Samples were collected during base flow periods (i.e., dry events) and rainfall events (i.e., wet events). The objectives of the study were to determine which pesticides were detectable, whether there was a difference in the detection frequency between the two watersheds and between upstream and downstream in each river, and whether precipitation influenced the frequency of detection. Eleven pesticides and one metabolite were detected in surface waters of the Don and Humber rivers or their tributaries, with approximately 72% of samples containing at least one pesticide attributable to lawn care use. The pesticides and pesticide metabolite detected in this study included 2,4-D, atrazine, bromacil, carbofuran, chlorpyrifos, cypermethrin, diazinon, dicamba, MECOPROP, metolachlor, metribuzin, and an atrazine metabolite (des-ethyl atrazine). Four pesticides exceeded federal or provincial water quality guidelines/objectives. Diazinon exceeded the provincial water quality objective in 28% of the samples taken. For the three other pesticides (atrazine, carbofuran and chlorpyrifos) exceedance of a water quality criteria occurred in less than 1% of the samples.     

Long-term recovery of pressurized water reactors following a large break loss-of-coolant accident

The U.S. Nuclear Regulatory Commission recently identified a possible safety concern for pressurized water reactors. Following the reflood phase of a large break loss-of-coolant accident, long-term cooling of the reactor core may not be ensured. Specifically, the concern is that, for a pump discharge cold leg break, the loop seals in the reactor coolant pump suction piping will refill with liquid and the post-reflood steam production may depress the liquid levels in the downflow sides of the loop seals. A loop seal depression would cause a corresponding depression of the core liquid levels and possibly a fuel rod heatup in the upper core region. This paper is intended as an introduction of the safety issue that: (1) describes the important aspects of the problem, (2) provides an initial analysis of the consequences, and (3) discusses ongoing work in this area. Because the elevation of the loop seals is near the mid-core elevation in plants of Westinghouse design, the concern is greatest for those plants. There is less concern for most plants of Combustion Engineering design, and likely no concern for plants of Babcock and Wilcox design. This issue was addressed by employing both steady-state and transient systems analysis approaches. Two approaches were used because of uncertainties regarding actual reactor coolant system behavior during the post-reflood period. The steady-state approach involved the development and application of a simple computer program to investigate reactor coolant system behavior assuming quiescent post-reflood conditions. The transient systems approach involved investigating this behavior using the RELAP5/MOD2 computer code and a comprehensive RELAP5 model of a Westinghouse pressurized water reactor. The steady-state analysis indicated only a moderate fuel rod heatup is possible. The transient systems analysis indicated boiling and condensation-induced flow oscillations are sufficient to prevent fuel rod heatup. Analysis uncertainties are discussed.     

An experimental investigation of triboelectrification in cohesive and non-cohesive pharmaceutical powders

A detailed experimental investigation has been undertaken of the triboelectrification process of the pharmaceutical excipient alpha-lactose monohydrate and selected drugs. Particle charge studies involved the design and construction of an apparatus to incorporate pneumatic powder feed, triboelectric charging via a cyclone separator and simultaneous powder charge (Q) and mass (M) measurements using a modified Faraday well. Preliminary studies showed the charging of the selected materials to be unaffected by relative humidity up to 84%, due to the very low hygroscopicity of the powders. Experiments using lactose size fractions with brass, steel and cellulose contact charging surfaces conducted at different feeder gas pressures, gave net electronegative specific charge values (Q/M) for the metal surfaces, and electropositive values for cellulose. Specific charge increased linearly with gas pressure for the metals, and non-linearly for cellulose. Samples of micronised lactose and beclomethasone dipropionate (BDP) showed more tendency than unmicronised samples to adhere to the contact surface which resulted in more complex charging processes. A novel system to analyse the charge and mass data in further detail was developed, giving relative Q/M values at unit time intervals. It is proposed that this will overcome the limitations of reliance on the final net specific charge value. Preliminary results indicated differences in the charging mechanism for lactose in contact with the two metal surfaces.     

A comparative study of thin film insulation techniques for gold electrodes

The increasing use of microelectrodes in small sample volumes and biological environments require the use of thin film insulators. The insulating ability of the thin film insulators electrophoretic paint, polyimide, allylphenol phenol copolymer and an epoxy dip coat have been assessed using gold wires coated in the relevant film. Insulation was assessed by recording the current from the wires in a solution of known redox couple. The effect of prolonged storage in aqueous solutions was also investigated. The most successful insulating approach, with regards to insulative ability, prolonged use in aqueous environments and speed of application, was the combination of cathodic electrophoretic paint followed by polyimide.     

Issues affecting advanced passive light-water reactor safety analysis

Next generation commercial reactor designs emphasize enhanced safety by means of improved safety system reliability and performance. These objectives are achieved via safety system simplification and reliance on immutable natural forces for system operation. Simulating the performance of these safety systems will be central to analytical safety evaluation of advanced passive reactor designs. Yet, the characteristically small driving forces of these safety systems pose challenging computational problems to current thermal-hydraulic systems analysis codes. Additionally, the safety systems generally interact closely with one another, requiring accurate, integrated simulation of the nuclear steam supply system, engineered safeguards and containment. Furthermore, numerical safety analysis of these advanced passive reactor designs will necessitate simulation of long-duration, slowly-developing transients compared with current reactor designs. The composite effects of small computational inaccuracies on induced system interactions and perturbations over long periods may well lead to predicted results which are significantly different than would otherwise be expected or might actually occur. Comparisons between the engineered safety features of competing U.S. advanced light water reactor designs and analogous present day reactor designs are examined relative to the adequacy of existing thermal-hydraulic safety codes in predicting the mechanisms of passive safety. Areas where existing codes may require modification, extension or assessment relative to passive safety designs are identified. Conclusions concerning the applicability of these codes to advanced passive light water reactor safety analysis are presented.     

Optimal control and energy storage for DC electric train systems using evolutionary algorithms

Railway Engineering Science - Electrified railways are becoming a popular transport medium and these consume a large amount of electrical energy. Environmental concerns demand reduction in energy...     

The electrochemistry of nitrate-amide melts: Reactions of nickel and copper in nitrate-amide melts

Copper and nickel may be electrodeposited from their ions in solution in nitrate-amide melts at room temperature. In the ammonium nitrate-acetamide-urea melt at 23°C, the reduction to the metal competes with the corrosion reaction at low rates and with the reduction of the ammonium and nitrate ions of the melt at high current densities. Two distinct types of nickel complexes are found in solution. The nickel complex formed by the corrosion reaction is bound by at least one ammonia ligand. Nickel complexes formed by dissolving the halide in the melt show evidence of coordination by less strongly bounding ligands, probably by amides. Similarly, the visible spectra of copper chloride in solution suggest that the cupric ions are coordinated primarily by amides. The copper corrosion reaction produces a complex with a spectra distinctly different from that of cupric chloride in solution. The shift in absorption maxima suggests that the copper complex formed by the corrosion reaction has at least one ammonia ligand in the coordination sphere.     

The Geometry of the Zodiac

The zodiac is widely known as a band of twelve celestial constellations. It also contains a mathematical model for cosmographic depiction, based on observations of the sun, moon, and visible planets as they traverse the celestial ecliptic. Here wee consider the zodiac as a timepiece or calendar; how this system of planets and constellations emerges from elementary geometric patterns; and how these patterns inform the symbols of the zodiac and frame our world view.