Simultaneous quantitation of phenobarbitone and p-hydroxyphenobarbitone and their perdeuteroethyl analogues in biological fluids by combined gas chromatography-mass spectrometry

In order to develop 5-pentadeuteroethyl-5-phenyl barbituric acid as an alternative tracer in pharmacokinetic and metabolic studies of phenobarbitone, and to search for possible isotope effects associated with such labelling, we propose a gas chromatographic-mass spectrometric assay for simultaneous measurement of phenobarbitone, p-hydroxyphenobarbitone and their perdeuteroethyl analogues, using [1,3-15N2,2-13C] phenobarbitone as internal standard. These compounds were extracted from plasma (50 microliter) or urine (500 microliter) and pentylated according to Greeley's method. Linear calibration curves were obtained in the concentration range from 0.5 to 3 micrograms/ml. The interday precision, mean accuracy and detection limit were 0.77-5.28%, 99.99-100.80% and 0.03-0.05 microgram/ml, respectively. Results for plasma and urine concentrations, and pharmacokinetic parameters in humans, are presented to illustrate this method.     

Three-dimensional blow-up solutions of the Navier-Stokes equations

In this paper we extend the plane blow-up results of Grundy& McLaughlin (1997) to the three-dimensional Navier-Stokes equations.Using a solution structure originally due to Lin we first providenumerical evidence for the existence of blow-up solutions on- < x, z < , 0 y 1 with boundary conditions on y = 0and y = 1 involving derivatives of the velocity components.The formulation enables us to consider plane and radial flowas special cases. Various features of the computations are isolatedand are used to construct a formal asymptotic solution closeto blow-up. We show that the numerical and asymptotic analysesprovide a mutually consistent global picture which supportsthe conclusion that, for the family of problems we considerhere, blow-up in fact can take place in three dimensions butat an inverse linear rate rather than the faster inverse squareof the plane case.     

Long-term retention of ice-nucleating active Pseudomonas fluorescens by overwintering colorado potato beetles

Ice nucleating-active Pseudomonas fluorescens F264C was fed to Colorado potato beetles to determine bacterial retentioin in the beetle gut and its effect on the cold hardiness of this insect pest. The bacrterium was present in beetles recovered after overwintering in the field, seven months after their exposure to P. fluorescens. Retention was evident not only in the detection of the P. fluorescens ice nucleating gene, inaW, in bacterial cultures from beetle guts but also in the elevated supercooling points of some treated beetles.     

Description of an individual patient methodology for calculating the cost-effectiveness of treatments for osteoporosis in women

Models of the cost-effectiveness of pharmaceutical interventions for the treatment of osteoporosis have traditionally adopted cohort-based approaches. We present a transition-state model to simulate the experience of individual patients, allowing the full patient history and residential status to influence the probabilities of future fractures at the hip, spine, wrist or proximal humerus. Alongside epidemiological data, we used systematic literature reviews of costs, utilities and efficacy to populate the model for a UK setting. We established a statistical relationship between the inputs and outputs of the individual patient model creating a near instantaneous emulation of the individual patient model. We undertook extensive sensitivity analyses to analyse the uncertainty in the estimated incremental cost per quality-adjusted life year due to uncertainty in the efficacy of the drugs. We provide illustrative results accompanied by individual and multi-interventional cost-effectiveness acceptability curves.     

The lifetime of the A2Sigmau+ state of the N3 radical

The lifetime of the A 2Sigmau+ state of N3 has been determined from line broadening in the rotationally resolved laser-induced fluorescence (LIF) spectrum of the A 2Sigmau+-X 2Pig transition. N3 radicals, produced by fluorine atom abstraction from HN3, were probed with an intracavity doubled ring laser operating near 272 nm. Careful examination of the LIF spectrum indicates a significant Lorentzian component to the line shape due to a rapid predissociation in the A 2Sigmau+ state. The predissociation lifetime is found to be 132+/-21 ps for the 000 vibrational level and 64+/-10 ps for the 010 level. The short lifetime is consistent with the low intensity of the LIF signal especially for the 010-010 hot band.