An econometric model of the American minor cycle,

Bibliography: p. 30-34.

Population pharmacokinetic analysis of mycophenolic acid in renal transplant recipients following oral administration of mycophenolate mofetil

Aim To develop a population pharmacokinetic model for mycophenolic acid in adult kidney transplant recipients, quantifying average population pharmacokinetic parameter values, and between- and within-subject variability and to evaluate the influence of covariates on the pharmacokinetic variability. Methods Pharmacokinetic data for mycophenolic acid and covariate information were previously available from 22 patients who underwent kidney transplantation at the Princess Alexandra Hospital. All patients received mycophenolate mofetil 1 g orally twice daily. A total of 557 concentration-time points were available. Data were analysed using the first-order method in NONMEM (version 5 level 1.1) using the G77 FORTRAN compiler. Results The best base model was a two-compartment model with a lag time (apparent oral clearance was 271 h(-1), and apparent volume of the central compartment 981). There was visual evidence of complex absorption and time-dependent clearance processes, but they could not be successfully modelled in this study. Weight was investigated as a covariate, but no significant relationship was determined. Conclusions The complexity in determining the pharmacokinetics of mycophenolic acid is currently underestimated. More complex pharmacokinetic models, though not supported by the limited data collected for this study, may prove useful in the future. The large between-subject and between-occasion variability and the possibility of nonlinear processes associated with the pharmacokinetics of mycophenolic acid raise questions about the value of the use of therapeutic monitoring and limited sampling strategies.

Analysis of population pharmacokinetic data using NONMEM and WinBUGS

The aim of this report is to describe the use of WinBUGS for two datasets that arise from typical population pharmacokinetic studies. The first dataset relates to gentamicin concentration-time data that arose as part of routine clinical care of 55 neonates. The second dataset incorporated data from 96 patients receiving enoxaparin. Both datasets were originally analyzed by using NONMEM. In the first instance, although NONMEM provided reasonable estimates of the fixed effects parameters it was unable to provide satisfactory estimates of the between-subject variance. In the second instance, the use of NONMEM resulted in the development of a successful model, albeit with limited available information on the between-subject variability of the pharmacokinetic parameters. WinBUGS was used to develop a model for both of these datasets. Model comparison for the enoxaparin dataset was performed by using the posterior distribution of the log-likelihood and a posterior predictive check. The use of WinBUGS supported the same structural models tried in NONMEM. For the gentamicin dataset a one-compartment model with intravenous infusion was developed, and the population parameters including the full between-subject variance-covariance matrix were available. Analysis of the enoxaparin dataset supported a two compartment model as superior to the one-compartment model, based on the posterior predictive check. Again, the full between-subject variance-covariance matrix parameters were available. Fully Bayesian approaches using MCMC methods, via WinBUGS, can offer added value for analysis of population pharmacokinetic data.

Atmospheric corrosion of copper and the colour, structure and composition of natural patinas on copper

This paper describes the results of atmospheric corrosion testing and of an examination of patina samples from Brisbane, Denmark, Sweden, France, USA and Austria. The aim was threefold: (1) to determine the structure of natural patinas and to relate their structure to their appearance in service and to the atmospheric corrosion of copper; (2) to understand why a brown rust coloured layer forms on the surface of some copper patinas; (3) to understand why some patinas are still black in colour despite being of significant age. During the atmospheric corrosion of copper, a two-layer patina forms on the copper surface. Cuprite is the initial corrosion product and cuprite is always the patina layer in contact with the copper. The growth laws describing patina formation indicate that the decreasing corrosion rate with increasing exposure time is due to the protective nature of the cuprite layer. The green patinas were typically characterised by an outer layer of brochantite, which forms as individual crystals on the surface of the cuprite layer, probably by a precipitation reaction from an aqueous surface layer on the cuprite layer. Natural patinas come in a variety of colours. The colour is controlled by the amount of the patina and its chemical composition. Thin patinas containing predominantly cuprite were black. If the patina was sufficiently thick, and the [Fe]/[Cu] ratio was low, then the patina was green, whereas if the [Fe]/[Cu] ratio was approximately 10 at%, then the patina is rust brown in colour. The iron was in solid solution in the brochantite, which might be designated as a (copper/iron) hydroxysulphate. In the brown patinas examined, the iron was distributed predominately in the outermost part of the patina. (c) 2005 Elsevier Ltd. All rights reserved.

Bayesian population pharmacokinetic analysis of sirolimus

Objective: It is usual that data collected from routine clinical care is sparse and unable to support the more complex pharmacokinetic (PK) models that may have been reported in previous rich data studies. Informative priors may be a pre-requisite for model development. The aim of this study was to estimate the population PK parameters of sirolimus using a fully Bayesian approach with informative priors. Methods: Informative priors including prior mean and precision of the prior mean were elicited from previous published studies using a meta-analytic technique. Precision of between-subject variability was determined by simulations from a Wishart distribution using MATLAB (version 6.5). Concentration-time data of sirolimus retrospectively collected from kidney transplant patients were analysed using WinBUGS (version 1.3). The candidate models were either one- or two-compartment with first order absorption and first order elimination. Model discrimination was based on computation of the posterior odds supporting the model. Results: A total of 315 concentration-time points were obtained from 25 patients. Most data were clustered at trough concentrations with range of 1.6 to 77 hours post-dose. Using informative priors, either a one- or two-compartment model could be used to describe the data. When a one-compartment model was applied, information was gained from the data for the value of apparent clearance (CL/F = 18.5 L/h), and apparent volume of distribution (V/F = 1406 L) but no information was gained about the absorption rate constant (ka). When a two-compartment model was fitted to the data, the data were informative about CL/F, apparent inter-compartmental clearance, and apparent volume of distribution of the peripheral compartment (13.2 L/h, 20.8 L/h, and 579 L, respectively). The posterior distribution of the volume distribution of central compartment and ka were the same as priors. The posterior odds for the two-compartment model was 8.1, indicating the data supported the two-compartment model. Conclusion: The use of informative priors supported the choice of a more complex and informative model that would otherwise have not been supported by the sparse data.

Intelligent decision support for family financial planning

In today’s financial markets characterized by constantly changing tax laws and increasingly complex transactions, the demand for family financial planning (FFP) services is rising dramatically. However, the current trend to develop advisory systems that focus mainly on the financial or investment side fails to consider the whole picture of FFP. Separating financial or investment advice from legal and accounting advice may result in conflicting advice or important omissions that could lead to users suffering financial loss. In this paper, we propose a conceptual model for FFP decision-making process, followed by a novel architecture to support an aggregated FFP decision process by utilizing intelligentagents and Web-services technology. A prototype system for supporting FFP decision is presented to demonstrate the advances of the proposed Web-service multi-agentsbased system architecture and business value.

Learning with noise and regularizers in multilayer neural networks

We study the effect of two types of noise, data noise and model noise, in an on-line gradient-descent learning scenario for general two-layer student network with an arbitrary number of hidden units. Training examples are randomly drawn input vectors labeled by a two-layer teacher network with an arbitrary number of hidden units. Data is then corrupted by Gaussian noise affecting either the output or the model itself. We examine the effect of both types of noise on the evolution of order parameters and the generalization error in various phases of the learning process.

The learning dynamics of a universal approximator

The learning properties of a universal approximator, a normalized committee machine with adjustable biases, are studied for on-line back-propagation learning. Within a statistical mechanics framework, numerical studies show that this model has features which do not exist in previously studied two-layer network models without adjustable biases, e.g., attractive suboptimal symmetric phases even for realizable cases and noiseless data.

Binocular interaction:Contrast matching and contrast discrimination are predicted by the same model

How do signals from the 2 eyes combine and interact? Our recent work has challenged earlier schemes in which monocular contrast signals are subject to square-law transduction followed by summation across eyes and binocular gain control. Much more successful was a new 'two-stage' model in which the initial transducer was almost linear and contrast gain control occurred both pre- and post-binocular summation. Here we extend that work by: (i) exploring the two-dimensional stimulus space (defined by left- and right-eye contrasts) more thoroughly, and (ii) performing contrast discrimination and contrast matching tasks for the same stimuli. Twenty-five base-stimuli made from 1 c/deg patches of horizontal grating, were defined by the factorial combination of 5 contrasts for the left eye (0.3-32%) with five contrasts for the right eye (0.3-32%). Other than in contrast, the gratings in the two eyes were identical. In a 2IFC discrimination task, the base-stimuli were masks (pedestals), where the contrast increment was presented to one eye only. In a matching task, the base-stimuli were standards to which observers matched the contrast of either a monocular or binocular test grating. In the model, discrimination depends on the local gradient of the observer's internal contrast-response function, while matching equates the magnitude (rather than gradient) of response to the test and standard. With all model parameters fixed by previous work, the two-stage model successfully predicted both the discrimination and the matching data and was much more successful than linear or quadratic binocular summation models. These results show that performance measures and perception (contrast discrimination and contrast matching) can be understood in the same theoretical framework for binocular contrast vision. © 2007 VSP.

Sustainable competitive advantage in electronic business: towards a contingency perspective of the resource-based view

Our understanding of the nature of competitive advantage has not been helped by a tendency for theorists to adopt a unitary position, suggesting, for example, that advantage is industry based or resource based. In examining the nature of competitive advantage in an electronic business (e-business) environment this paper adopts a contingency perspective. Several intriguing questions emerge. Do 'new economy' companies have different resource profiles to 'old economy' companies? Are the patterns of resource development and accumulation different? Are attained advantages less sustainable for e-businesses? These are the kinds of themes examined in this paper. The literature on competitive advantage is reviewed as are the challenges posed by the recent changes in the business environment.Two broad sets of firms are identified as emerging out of the e-business shake up and the resource profiles of these firms are discussed. Several research propositions are advanced and the implications for research and practice are discussed.

Interocular masking and summation indicate two stages of divisive contrast gain control

Our understanding of early spatial vision owes much to contrast masking and summation paradigms. In particular, the deep region of facilitation at low mask contrasts is thought to indicate a rapidly accelerating contrast transducer (eg a square-law or greater). In experiment 1, we tapped an early stage of this process by measuring monocular and binocular thresholds for patches of 1 cycle deg-1 sine-wave grating. Threshold ratios were around 1.7, implying a nearly linear transducer with an exponent around 1.3. With this form of transducer, two previous models (Legge, 1984 Vision Research 24 385 - 394; Meese et al, 2004 Perception 33 Supplement, 41) failed to fit the monocular, binocular, and dichoptic masking functions measured in experiment 2. However, a new model with two-stages of divisive gain control fits the data very well. Stage 1 incorporates nearly linear monocular transducers (to account for the high level of binocular summation and slight dichoptic facilitation), and monocular and interocular suppression (to fit the profound 42 Oral presentations: Spatial vision Thursday dichoptic masking). Stage 2 incorporates steeply accelerating transduction (to fit the deep regions of monocular and binocular facilitation), and binocular summation and suppression (to fit the monocular and binocular masking). With all model parameters fixed from the discrimination thresholds, we examined the slopes of the psychometric functions. The monocular and binocular slopes were steep (Weibull ߘ3-4) at very low mask contrasts and shallow (ߘ1.2) at all higher contrasts, as predicted by all three models. The dichoptic slopes were steep (ߘ3-4) at very low contrasts, and very steep (ß>5.5) at high contrasts (confirming Meese et al, loco cit.). A crucial new result was that intermediate dichoptic mask contrasts produced shallow slopes (ߘ2). Only the two-stage model predicted the observed pattern of slope variation, so providing good empirical support for a two-stage process of binocular contrast transduction. [Supported by EPSRC GR/S74515/01]

Modelling the innovation value chain

Innovation events – the introduction of new products or processes – represent the end of a process of knowledge sourcing and transformation. They also represent the beginning of a process of exploitation which may result in an improvement in the performance of the innovating business. This recursive process of knowledge sourcing, transformation and exploitation comprises the innovation value chain. Modelling the innovation value chain for a large group of manufacturing firms in Ireland and Northern Ireland highlights the drivers of innovation, productivity and firm growth. In terms of knowledge sourcing,we find strong complementarity between horizontal, forwards, backwards, public and internal knowledge sourcing activities. Each of these forms of knowledge sourcing also makes a positive contribution to innovation in both products and processes although public knowledge sources have only an indirect effect on innovation outputs. In the exploitation phase, innovation in both products and processes contribute positively tocompany growth, with product innovation having a short-term ‘disruption’ effect on labour productivity. Modelling the complete innovation value chain highlights the structure and complexity of the process of translating knowledge into business value and emphasises the role of skills, capital investment and firms’ other resources in the value creation process.

The innovation value chain

Innovation events - the introduction of new products or processes - represent the end of a process of knowledge sourcing and transformation. They also represent the beginning of a process of exploitation which may result in an improvement in the performance of the innovating business. This recursive process of knowledge sourcing, transformation and exploitation we call the innovation value chain. Modelling the innovation value chain for a large group of manufacturing firms in Ireland and Northern Ireland highlights the drivers of innovation, productivity and firm growth. In terms of knowledge sourcing, we find strong complementarity between horizontal, forwards, backwards, public and internal knowledge sourcing activities. Each of these forms of knowledge sourcing also makes a positive contribution to innovation in both products and processes although public knowledge sources have only an indirect effect on innovation outputs. In the exploitation phase, innovation in both products and processes contribute positively to company growth, with product innovation having a short-term ‘disruption’ effect on labour productivity. Modelling the complete innovation value chain highlights the structure and complexity of the process of translating knowledge into business value and emphasises the role of skills, capital investment and firms’ other resources in the value creation process.

Mass transfer characteristics of two-aqueous-phase liquid-liquid mixtures

Mass transfer rates were studied using the falling drop method. Cibacron Blue 3 GA dye was the transferring solute from the salt phase to the PEG phase. Measurements were undertaken for several concentrations of the dye and the phase-forming solutes and with a range of different drop sizes, e.g. 2.8, 3.0 and 3.7 mm. The dye was observed to be present in the salt phase as finely dispersed solids but a model confirmed that the mass transfer process could still be described by an equation based upon the Whitman two-film model. The overall mass transfer coefficient increased with increasing concentration of the dye. The apparent mass transfer coefficient ranged from 1 x 10-5 to 2 x 10 -4 m/s. Further experiments suggested that mass transfer was enhanced at high concentration by several mechanisms. The dye was found to change the equilibrium composition of the two phases, leading to transfer of salt between the drop and continuous phases. It also lowered the interfacial tension (i.e. from 1.43 x 10-4 N/m for 0.01% w/w dye concentration to 1.07 x 10-4 N/m for 0.2% w/w dye concentration) between the two phases, which could have caused interfacial instabilities (Marangoni effects). The largest drops were deformable, which resulted in a significant increase in the mass transfer rate. Drop size distribution and Sauter mean drop diameter were studied on-line in a 1 litre agitated vessel using a laser diffraction technique. The effects of phase concentration, dispersed phase hold-up and impeller speed were investigated for the salt-PEG system. An increase in agitation speed in the range 300 rpm to 1000 rpm caused a decrease in mean drop diameter, e.g. from 50 m to 15 m. A characteristic bimodal drop size distribution was established within a very short time. An increase in agitation rate caused a shift of the larger drop size peak to a smaller size.

Efficient THz radiation from a nanocrystalline silicon-based multi-layer photomixer

In this paper we propose a novel type of multiple-layer photomixer based on amorphous/nano-crystalline-Si. Such a device implies that it could be possible to enhance the conversion efficiency from optical power to THz emission by increasing the absorption length and by reducing the device overheating through the use of substrates with higher thermal conductivity compared to GaAs. Our calculations show that the output power from a two-layer Si-based photomixer is at least ten times higher than that from conventional LT-GaAs photomixers at 1 THz.