Estimation of pharmacokinetic parameters from non-compartmental variables using Microsoft Excel((R))

This study was conducted to develop a method, termed 'back analysis (BA)', for converting non-compartmental variables to compartment model dependent pharmacokinetic parameters for both one- and two-compartment models. A Microsoft Excel((R)) spreadsheet was implemented with the use of Solver((R)) and visual basic functions. The performance of the BA method in estimating pharmacokinetic parameter values was evaluated by comparing the parameter values obtained to a standard modelling software program, NONMEM, using simulated data. The results show that the BA method was reasonably precise and provided low bias in estimating fixed and random effect parameters for both one- and two-compartment models. The pharmacokinetic parameters estimated from the BA method were similar to those of NONMEM estimation.

A composite DOP approach to excluding bottom reflectance in mapping water parameters of shallow coastal zones from TM imagery

In this paper we proposed a composite depth of penetration (DOP) approach to excluding bottom reflectance in mapping water quality parameters from Landsat thematic mapper (TM) data in the shallow coastal zone of Moreton Bay, Queensland, Australia. Three DOPs were calculated from TM1, TM2 and TM3, in conjunction with bathymetric data, at an accuracy ranging from +/-5% to +/-23%. These depths were used to segment the image into four DOP zones. Sixteen in situ water samples were collected concurrently with the recording of the satellite image. These samples were used to establish regression models for total suspended sediment (TSS) concentration and Secchi depth with respect to a particular DOP zone. Containing identical bands and their transformations for both parameters, the models are linear for TSS concentration, logarithmic for Secchi depth. Based on these models, TSS concentration and Secchi depth were mapped from the satellite image in respective DOP zones. Their mapped patterns are consistent with the in situ observed ones. Spatially, overestimation and underestimation of the parameters are restricted to localised areas but related to the absolute value of the parameters. The mapping was accomplished more accurately using multiple DOP zones than using a single zone in shallower areas. The composite DOP approach enables the mapping to be extended to areas as shallow as <3 m. (C) 2004 Elsevier Inc. All rights reserved.

Changes in body water distribution during treatment with inhaled steroid in pre-school children

Primary objective: The study aimed to examine the changes in water distribution in the soft tissue during systemic steroid activity. Research design: A three-way cross-over, randomized, placebo-controlled, double-blind trial was used, including 4 weeks of fluticasone propionate pMDI 200 mug b.i.d. delivered via Babyhaler(R), budesonide pressurized metered dose inhaler (pMDI) 200 mug b.i.d. delivered via Nebuchamber(R) and placebo. Spacers were primed before use. In total, 40 children aged 1-3 years, with mild intermittent asthma were included. Twenty-five of the children completed all three treatments. At the end of each treatment period body impedance and skin ultrasonography were measured. Methods and procedures: We measured changes in water content of the soft tissues by two methods. Skin ultrasonography was used to detect small changes in dermal water content, and bioelectrical impedance was used to assess body water content and distribution. Main outcomes and results: We found an increase in skin density of the shin from fluticasone as measured by ultrasonography (p = 0.01). There was a tendency for a consistent elevation of impedance parameters from active treatments compared to placebo although overall this effect was not statistically significant (0.1< p <0.2). However, sub-analyses indicated a significant effect on whole-body and leg impedance from budesonide treatment (p <0.05). Conclusion: Decreased growth during inhaled steroid treatment seems to partly reflect generalized changes in body water.

Prediction of the growth of wear-type rail corrugation

The growth behaviour of the vibrational wear phenomenon known as rail corrugation is investigated analytically and numerically using mathematical models. A simplified feedback model for wear-type rail corrugation that includes a wheel pass time delay is developed with an aim to analytically distil the most critical interaction occurring between the wheel/rail structural dynamics, rolling contact mechanics and rail wear. To this end, a stability analysis on the complete system is performed to determine the growth of wear-type rail corrugations over multiple wheelset passages. This analysis indicates that although the dynamical behaviour of the system is stable for each wheel passage, over multiple wheelset passages, the growth of wear-type corrugations is shown to be the result of instability due to feedback interaction between the three primary components of the model. The corrugations are shown analytically to grow for all realistic railway parameters. From this analysis an analytical expression for the exponential growth rate of corrugations in terms of known parameters is developed. This convenient expression is used to perform a sensitivity analysis to identify critical parameters that most affect corrugation growth. The analytical predictions are shown to compare well with results from a benchmarked time-domain finite element model. (C) 2004 Elsevier B.V. All rights reserved.

Efficient -tensor determination and NH assignment of paramagnetic proteins

Anisotropic magnetic susceptibility tensors chi of paramagnetic metal ions are manifested in pseudocontact shifts, residual dipolar couplings, and other paramagnetic observables that present valuable long-range information for structure determinations of protein-ligand complexes. A program was developed for automatic determination of the chi-tensor anisotropy parameters and amide resonance assignments in proteins labeled with paramagnetic metal ions. The program requires knowledge of the three-dimensional structure of the protein, the backbone resonance assignments of the diamagnetic protein, and a pair of 2D N-15-HSQC or 3D HNCO spectra recorded with and without paramagnetic metal ion. It allows the determination of reliable chi-tensor anisotropy parameters from 2D spectra of uniformly N-15-labeled proteins of fairly high molecular weight. Examples are shown for the 185-residue N-terminal domain of the subunit epsilon from E. coli DNA polymerase III in complex with the subunit theta and La3+ in its diamagnetic and Dy3+, Tb3+, and Er3+ in its paramagnetic form.

Infrared microspectroscopic mapping of the homogeneity of extruded blends: Application to starch/polyester blends

Blends of starch and a biodegradable polyester, produced by an extrusion process, which included a cross-linker/compatibilizer (maleic anhydride) and an initiator (dicumyl peroxide), were studied by infrared (IR) microspectroscopy using an attenuated total reflectance (ATR) objective. Extruded material, which had a diameter of about 3 mm, was sectioned and embedded in epoxy resin prior to IR analysis. Spectra were collected in a grid pattern across the sectioned face of the sample. Measurement of various band parameters from the spectra allowed IR maps to be constructed containing semi-quantitative information about the distribution of blend components. These maps showed the quality of the blend on a microscopic scale and showed how it varied with different concentrations of compatibilizer and initiator. (c) 2005 Elsevier Ltd. All rights reserved.

Negative second virial coefficients as predictors of protein crystal growth: Evidence from sedimentation equilibrium studies that refutes the designation of those light scattering parameters as osmotic virial coefficients

The effects of ammonium sulphate concentration on the osmotic second virial coefficient (B-AA/M-A) for equine serum albumin (pH 5.6, 20 degrees C) have been examined by sedimentation equilibrium. After an initial steep decrease with increasing ammonium sulphate concentration, B-AA/M-A assumes an essentially concentration-independent magnitude of 8-9 ml/g. Such behaviour conforms with the statistical-mechanical prediction that a sufficient increase in ionic strength should effectively eliminate the contributions of charge interactions to B-AA/M-A but have no effect on the covolume contribution (8.4 ml/g for serum albumin). A similar situation is shown to apply to published sedimentation equilibrium data for lysozyme (pH 4.5). Although termed osmotic second virial coefficients and designated as such (B-22), the negative values obtained in published light scattering studies of both systems have been described incorrectly because of the concomitant inclusion of the protein-salt contribution to thermodynamic nonideality of the protein. Those negative values are still valid predictors of conditions conducive to crystal growth inasmuch as they do reflect situations in which there is net attraction between protein molecules. However, the source of attraction responsible for the negative virial coefficient stems from the protein-salt rather than the protein-protein contribution, which is necessarily positive. (c) 2005 Elsevier B.V. All rights reserved.