Development and formulation of wax-based transdermal drug delivery systems

Topical and transdermal formulations are promising platforms for the delivery of drugs. A unit dose topical or transdermal drug delivery system that optimises the solubility of drugs within the vehicle provides a novel dosage form for efficacious delivery that also offers a simple manufacture technique is desirable. This study used Witepsol® H15 wax as a abase for the delivery system. One aspect of this project involved determination of the solubility of ibuprofen, flurbiprofen and naproxen in the was using microscopy, Higuchi release kinetics, HyperDSC and mathematical modelling techniques. Correlations between the results obtained via these techniques were noted with additional merits such as provision of valuable information on drug release kinetics and possible interactions between the drug and excipients. A second aspect of this project involved the incorporation of additional excipients: Tween 20 (T), Carbopol®971 (C) and menthol (M) to the wax formulation. On in vitro permeation through porcine skin, the preferred formulations were: ibuprofen (5% w/w) within Witepsol®H15 + 1% w/w T; flurbiprofen (10% w/w) within Witepsol®H15 + 1% w/w T; naproxen (5% w/w) within Witepsol®H15 + 1% w/w T + 1% C and sodium diclofenac (10% w/w) within Witepsol®H15 + 1% w/w T + 1% w/w T + 1% w/w C + 5% w/w M. Unit dose transdermal tablets containing ibuprofen and diclofenac were produced with improved flux compared to marketed products; Voltarol Emugel® demonstrated flux of 1.68x10-3 cm/h compared to 123 x 10-3 cm/h for the optimised product as detailed above; Ibugel Forte® demonstrated a permeation coefficient value of 7.65 x 10-3 cm/h compared to 8.69 x 10-3 cm/h for the optimised product as described above.

Dynamic QoS management and optimisation in service-based systems

Service-based systems that are dynamically composed at run time to provide complex, adaptive functionality are currently one of the main development paradigms in software engineering. However, the Quality of Service (QoS) delivered by these systems remains an important concern, and needs to be managed in an equally adaptive and predictable way. To address this need, we introduce a novel, tool-supported framework for the development of adaptive service-based systems called QoSMOS (QoS Management and Optimisation of Service-based systems). QoSMOS can be used to develop service-based systems that achieve their QoS requirements through dynamically adapting to changes in the system state, environment and workload. QoSMOS service-based systems translate high-level QoS requirements specified by their administrators into probabilistic temporal logic formulae, which are then formally and automatically analysed to identify and enforce optimal system configurations. The QoSMOS self-adaptation mechanism can handle reliability- and performance-related QoS requirements, and can be integrated into newly developed solutions or legacy systems. The effectiveness and scalability of the approach are validated using simulations and a set of experiments based on an implementation of an adaptive service-based system for remote medical assistance.

Knowledge-based systems and engineering software

The work described was carried out as part of a collaborative Alvey software engineering project (project number SE057). The project collaborators were the Inter-Disciplinary Higher Degrees Scheme of the University of Aston in Birmingham, BIS Applied Systems Ltd. (BIS) and the British Steel Corporation. The aim of the project was to investigate the potential application of knowledge-based systems (KBSs) to the design of commercial data processing (DP) systems. The work was primarily concerned with BIS's Structured Systems Design (SSD) methodology for DP systems development and how users of this methodology could be supported using KBS tools. The problems encountered by users of SSD are discussed and potential forms of computer-based support for inexpert designers are identified. The architecture for a support environment for SSD is proposed based on the integration of KBS and non-KBS tools for individual design tasks within SSD - The Intellipse system. The Intellipse system has two modes of operation - Advisor and Designer. The design, implementation and user-evaluation of Advisor are discussed. The results of a Designer feasibility study, the aim of which was to analyse major design tasks in SSD to assess their suitability for KBS support, are reported. The potential role of KBS tools in the domain of database design is discussed. The project involved extensive knowledge engineering sessions with expert DP systems designers. Some practical lessons in relation to KBS development are derived from this experience. The nature of the expertise possessed by expert designers is discussed. The need for operational KBSs to be built to the same standards as other commercial and industrial software is identified. A comparison between current KBS and conventional DP systems development is made. On the basis of this analysis, a structured development method for KBSs in proposed - the POLITE model. Some initial results of applying this method to KBS development are discussed. Several areas for further research and development are identified.

User interface design support for the development of knowledge-based systems

The present scarcity of operational knowledge-based systems (KBS) has been attributed, in part, to an inadequate consideration shown to user interface design during development. From a human factors perspective the problem has stemmed from an overall lack of user-centred design principles. Consequently the integration of human factors principles and techniques is seen as a necessary and important precursor to ensuring the implementation of KBS which are useful to, and usable by, the end-users for whom they are intended. Focussing upon KBS work taking place within commercial and industrial environments, this research set out to assess both the extent to which human factors support was presently being utilised within development, and the future path for human factors integration. The assessment consisted of interviews conducted with a number of commercial and industrial organisations involved in KBS development; and a set of three detailed case studies of individual KBS projects. Two of the studies were carried out within a collaborative Alvey project, involving the Interdisciplinary Higher Degrees Scheme (IHD) at the University of Aston in Birmingham, BIS Applied Systems Ltd (BIS), and the British Steel Corporation. This project, which had provided the initial basis and funding for the research, was concerned with the application of KBS to the design of commercial data processing (DP) systems. The third study stemmed from involvement on a KBS project being carried out by the Technology Division of the Trustees Saving Bank Group plc. The preliminary research highlighted poor human factors integration. In particular, there was a lack of early consideration of end-user requirements definition and user-centred evaluation. Instead concentration was given to the construction of the knowledge base and prototype evaluation with the expert(s). In response to this identified problem, a set of methods was developed that was aimed at encouraging developers to consider user interface requirements early on in a project. These methods were then applied in the two further projects, and their uptake within the overall development process was monitored. Experience from the two studies demonstrated that early consideration of user interface requirements was both feasible, and instructive for guiding future development work. In particular, it was shown a user interface prototype could be used as a basis for capturing requirements at the functional (task) level, and at the interface dialogue level. Extrapolating from this experience, a KBS life-cycle model is proposed which incorporates user interface design (and within that, user evaluation) as a largely parallel, rather than subsequent, activity to knowledge base construction. Further to this, there is a discussion of several key elements which can be seen as inhibiting the integration of human factors within KBS development. These elements stem from characteristics of present KBS development practice; from constraints within the commercial and industrial development environments; and from the state of existing human factors support.

A method for automatically eliciting node weights in a hierarchical knowledge-based structure for reasoning with uncertainty

Hierarchical knowledge structures are frequently used within clinical decision support systems as part of the model for generating intelligent advice. The nodes in the hierarchy inevitably have varying influence on the decisionmaking processes, which needs to be reflected by parameters. If the model has been elicited from human experts, it is not feasible to ask them to estimate the parameters because there will be so many in even moderately-sized structures. This paper describes how the parameters could be obtained from data instead, using only a small number of cases. The original method [1] is applied to a particular web-based clinical decision support system called GRiST, which uses its hierarchical knowledge to quantify the risks associated with mental-health problems. The knowledge was elicited from multidisciplinary mental-health practitioners but the tree has several thousand nodes, all requiring an estimation of their relative influence on the assessment process. The method described in the paper shows how they can be obtained from about 200 cases instead. It greatly reduces the experts’ elicitation tasks and has the potential for being generalised to similar knowledge-engineering domains where relative weightings of node siblings are part of the parameter space.

Nonlinear spectral shaping and optical rogue events in fiber-based systems

We provide an overview of our recent work on the shaping and stability of optical continua in the long pulse regime. Fibers with normal group-velocity dispersion at all-wavelengths are shown to allow for highly coherent continua that can be nonlinearly shaped using appropriate initial conditions. In contrast, supercontinua generated in the anomalous dispersion regime are shown to exhibit large fluctuations in the temporal and spectral domains that can be controlled using a carefully chosen seed. A particular example of this is the first experimental observation of the Peregrine soliton which constitutes a prototype of optical rogue-waves.

The mosaic test:benchmarking colour-based image retrieval systems using image mosaics

Evaluation and benchmarking in content-based image retrieval has always been a somewhat neglected research area, making it difficult to judge the efficacy of many presented approaches. In this paper we investigate the issue of benchmarking for colour-based image retrieval systems, which enable users to retrieve images from a database based on lowlevel colour content alone. We argue that current image retrieval evaluation methods are not suited to benchmarking colour-based image retrieval systems, due in main to not allowing users to reflect upon the suitability of retrieved images within the context of a creative project and their reliance on highly subjective ground-truths. As a solution to these issues, the research presented here introduces the Mosaic Test for evaluating colour-based image retrieval systems, in which test-users are asked to create an image mosaic of a predetermined target image, using the colour-based image retrieval system that is being evaluated. We report on our findings from a user study which suggests that the Mosaic Test overcomes the major drawbacks associated with existing image retrieval evaluation methods, by enabling users to reflect upon image selections and automatically measuring image relevance in a way that correlates with the perception of many human assessors. We therefore propose that the Mosaic Test be adopted as a standardised benchmark for evaluating and comparing colour-based image retrieval systems.

Phase shift keyed systems based on a gain switched laser transmitter

Return-to-Zero (RZ) and Non-Return-to-Zero (NRZ) Differential Phase Shift Keyed (DPSK) systems require cheap and optimal transmitters for widespread implementation. The authors report on a gain switched Discrete Mode (DM) laser that can be employed as a cost efficient transmitter in a 10.7 Gb/s RZ DPSK system and compare its performance to that of a gain switched Distributed Feed-Back (DFB) laser. Experimental results show that the gain switched DM laser readily provides error free performance and a receiver sensitivity of -33.1 dBm in the 10.7 Gbit/s RZ DPSK system. The standard DFB laser on the other hand displays an error floor at 10(-1) in the same RZ DPSK system. The difference in performance, between the two types of gain switched transmitters, is analysed by investigating their linewidths. We also demonstrate, for the first time, the generation of a highly coherent gain switched pulse train which displays a spectral comb of approximately 13 sidebands spaced by the 10.7 GHz modulation frequency. The filtered side-bands are then employed as narrow linewidth Continuous Wave (CW) sources in a 10.7 Gb/s NRZ DPSK system.

Electronic dispersion compensation using full optical-field reconstruction in 10Gbit/s OOK based systems

We investigate the design of electronic dispersion compensation (EDC) using full optical-field reconstruction in 10Gbit/s on-off keyed transmission systems limited by optical signal-to-noise ratio (OSNR). By effectively suppressing the impairment due to low- frequency component amplification in phase reconstruction, properly designing the transmission system configuration to combat fiber nonlinearity, and successfully reducing the vulnerability to thermal noise, a 4.8dB OSNR margin can be achieved for 2160km single-mode fiber transmission without any optical dispersion compensation. We also investigate the performance sensitivity of the scheme to various system parameters, and propose a novel method to greatly enhance the tolerance to differential phase misalignment of the asymmetric Mach-Zehnder interferometer. This numerical study provides important design guidelines which will enable full optical-field EDC to become a cost-effective dispersion compensation solution for future transparent optical networks.

Passive regeneration in 40 Gbit/s-based WDM dispersion-managed RZ transmission systems by in-line NOLMs

All-optical passive regeneration in 40 Gbit/s-based wavelength-division-multiplexed (WDM) dispersion-managed return-to-zero (RZ) transmission system was discussed. In-line nonlinear optical loop mirrors (NOLM) were used. A feasibility of 300 GHz-spaced two channel unlimited transmission and 150 GHz-spaced two channel 25000 km transmission over the standard fiber were found.

Comparison of vesicle based antigen delivery systems for delivery of hepatitis B surface antigen

There is a clinical need for a more effective vaccine against hepatitis B, and in particular vaccines that may be suitable for therapeutic administration. This study assesses the potential of cationic surfactant vesicle based formulations using two agents; the cationic amine containing [N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) or dimethyl dioctadecylammonium bromide (DDA) with hepatitis B surface antigen (HBsAg). Synthetic mycobacterial cord factor, trehalose 6,6′-dibehenate (TDB) has been used as an adjuvant and the addition of 1-monopalmitoyl glycerol (C16:0) (MP) and cholesterol (Chol) to DDA-TDB is assessed for its potential to facilitate formation of dehydration-rehydration vesicles (DRV) at room temperature, and the effect of this on immune responses. A DRV formulation is directly compared to an adsorbed formulation of the same composition and preparation protocol (MP:dioleoyl phosphoethanolamine (DOPE):Chol:DC-Chol) and the direct substitution of MP with phosphatidylcholine (PC) is also compared in DRV antigen-entrapped formulations. MP and Chol were shown to facilitate the use of DDA-TDB in DRV formulations prepared at room temperature, whilst there was marginal alteration of immunogenicity (a reduction in HBsAg-specific IL-2). The HBsAg adsorbed DRV formulation was not significantly different from the HBsAg entrapped DRV formulation. Overall, DDA formulations incorporating TDB showed markedly increased antigen specific splenocyte proliferation and elicited cytokine production concomitant with a strong T cell driven response, delineating formulations that may be useful for further evaluation of their clinical potential. © 2007 Elsevier B.V. All rights reserved.

Market-awareness in service-based systems

Service-based systems are applications built by composing pre-existing services. During design time and according to the specifications, a set of services is selected. Both, service providers and consumers exist in a service market that is constantly changing. Service providers continuously change their quality of services (QoS), and service consumers can update their specifications according to what the market is offering. Therefore, during runtime, the services are periodically and manually checked to verify if they still satisfy the specifications. Unfortunately, humans are overwhelmed with the degree of changes exhibited by the service market. Consequently, verification of the compliance specification and execution of the corresponding adaptations when deviations are detected cannot be carried out in a manual fashion. In this work, we propose a framework to enable online awareness of changes in the service market in both consumers and providers by representing them as active software agents. At runtime, consumer agents concretize QoS specifications according to the available market knowledge. Services agents are collectively aware of themselves and of the consumers' requests. Moreover, they can create and maintain virtual organizations to react actively to demands that come from the market. In this paper we show preliminary results that allow us to conclude that the creation and adaptation of service-based systems can be carried out by a self-organized service market system. © 2012 IEEE.