Sex differences in plasma clozapine and norclozapine concentrations in clinical practice and in relation to body mass index and plasma glucose concentrations: a retrospective survey

Background Clozapine is widely prescribed and, although effective, can cause weight gain and dysglycemia. The dysmetabolic effects of clozapine are thought to be more prevalent in women with this gender on average attaining 17 % higher plasma clozapine concentrations than men. Methods We investigated the relationship between dose, body mass index (BMI), plasma glucose concentration, and plasma clozapine and N-desmethylclozapine (norclozapine) concentrations in 100 individuals with a severe enduring mental illness. Results Mean (10th/90th percentile) plasma clozapine concentrations were higher for women [0.49 (0.27–0.79) mg/L] compared with men [0.44 (0.26–0.70) mg/L] (F = 2.2; p = 0.035). There was no significant gender difference in the prescribed clozapine dose. BMI was significantly higher in women [mean (95 % CI) = 34.5 (26.0–45.3)] for females compared with 32.5 (25.2–41.0) for males. Overall, BMI increased by 0.7 kg/m 2 over a mean follow-up period of 210 days. A lower proportion, 41 % of women had a fasting blood glucose ≤6.0 mmol/L (<6.0 mmol/L is defined by the International Diabetes Federation as normal glucose handling), compared with 88 % of men (χ2  = 18.6, p < 0.0001). Conclusions We have shown that mean BMI and blood glucose concentrations are higher in women prescribed clozapine than in men. Women also tended to attain higher plasma clozapine concentrations than men. The higher BMI and blood glucose in women may relate to higher tissue exposure to clozapine, as a consequence of sex differences in drug metabolism

Shuttle flight pressure instrumentation: Experience and lessons for the future

Flight data obtained from the Space Transportation System orbiter entries are processed and analyzed to assess the accuracy and performance of the Development Flight Instrumentation (DFI) pressure measurement system. Selected pressure measurements are compared with available wind tunnel and computational data and are further used to perform air data analyses using the Shuttle Entry Air Data System (SEADS) computation technique. The results are compared to air data from other sources. These comparisons isolate and demonstrate the effects of the various limitations of the DFI pressure measurement system. The effects of these limitations on orbiter performance analyses are addressed, and instrumentation modifications are recommended to improve the accuracy of similar fight data systems in the future

Radion Potential and Brane Dynamics

We examine the cosmology of the Randall-Sundrum model in a dynamic setting where scalar fields are present in the bulk as well as the branes. This generates a mechanism similar to that of Goldberger-Wise for radion stabilization and the recovery of late-cosmology features in the branes. Due to the induced radion dynamics, the inflating branes roll towards the minimum of the radion potential, thereby exiting inflation and reheating the Universe. In the slow roll part of the potential, the 'TeV' branes have maximum inflation rate and energy as their coupling to the radion and bulk modes have minimum suppresion. Hence, when rolling down the steep end of the potential towards the stable point, the radion field (which appears as the inflaton of the effective 4D theory in the branes) decays very fast, reheats the Universe .This process results decayin a decrease of brane's canonical vacuum energy $\Lambda_4$. However, at the minimum of the potential $\Lambda_4$ is small but not neccessarily zero and the fine-tuning issue remains .Density perturbation constraints introduce an upper bound when the radion stabilizies. Due to the large radion mass and strong suppression to the bulk modes, moduli problems and bulk reheating do not occur. The reheat temperature and a sufficient number of e-folding constraints for the brane-universe are also satisfied. The model therefore recovers the radiation dominated FRW universe.Comment: 16 pages, 3 figures,extraneous sentences removed, 2 footnotes added, some typos correcte

Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map

Peer reviewedPublisher PD

Bounds on negative energy densities in flat spacetime

We generalise results of Ford and Roman which place lower bounds -- known as quantum inequalities -- on the renormalised energy density of a quantum field averaged against a choice of sampling function. Ford and Roman derived their results for a specific non-compactly supported sampling function; here we use a different argument to obtain quantum inequalities for a class of smooth, even and non-negative sampling functions which are either compactly supported or decay rapidly at infinity. Our results hold in $d$-dimensional Minkowski space ($d\ge 2$) for the free real scalar field of mass $m\ge 0$. We discuss various features of our bounds in 2 and 4 dimensions. In particular, for massless field theory in 2-dimensional Minkowski space, we show that our quantum inequality is weaker than Flanagan's optimal bound by a factor of 3/2.Comment: REVTeX, 13 pages and 2 figures. Minor typos corrected, one reference adde

M-grid: Using Ubiquitous Web Technologies to create a Computational Grid

There are many potential users and uses for grid computing. However, the concept of sharing computing resources excites security concerns and, whilst being powerful and flexible, at least for novices, existing systems are complex to install and use. Together these represent a significant barrier to potential users who are interested to see what grid computing can do. This paper describes m-grid, a system for building a computational grid which can accept tasks from any user with access to a web browser and distribute them to almost any machine with access to the internet and manages to do this without the installation of additional software or interfering with existing security arrangements

Quantum Weak Energy Inequalities for the Dirac field in Flat Spacetime

Quantum Weak Energy Inequalities (QWEIs) have been established for a variety of quantum field theories in both flat and curved spacetimes. Dirac fields are known (by a result of Fewster and Verch) to satisfy QWEIs under very general circumstances. However this result does not provide an explicit formula for the QWEI bound, so its magnitude has not previously been determined. In this paper we present a new and explicit QWEI bound for Dirac fields of arbitrary mass in four-dimensional Minkowski space. We follow the methods employed by Fewster and Eveson for the scalar field, modified to take account of anticommutation relations. A key ingredient is an identity for Fourier transforms established by Fewster and Verch. We also compare our QWEI with those previously obtained for scalar and spin-1 fields.Comment: 8 pages, REVTeX4, version to appear in Phys Rev