Structure and activity in assessing antioxidant activity in vitro and in vivo:a critical appraisal illustrated with the flavonoids

Structure–activity relationships are indispensable to identify the most optimal antioxidants. The advantages of in vitro over in vivo experiments for obtaining these relationships are, that the structure is better defined in vitro, since less metabolism takes place. It is also the case that the concentration, a parameter that is directly linked to activity, is more accurately controlled. Moreover, the reactions that occur in vivo, including feed-back mechanisms, are often too multi-faceted and diverse to be compensated for during the assessment of a single structure–activity relationship. Pitfalls of in vitro antioxidant research include: (i) by definition, antioxidants are not stable and substantial amounts of oxidation products are formed and (ii) during the scavenging of reactive species, reaction products of the antioxidants accumulate. Another problem is that the maintenance of a defined concentration of antioxidants is subject to processes such as oxidation and the formation of reaction products during the actual antioxidant reaction, as well as the compartmentalization of the antioxidant and the reactive species in the in vitro test system. So determinations of in vitro structure-activity relationships are subject to many competing variables and they should always be evaluated critically. (c) 2005 Published by Elsevier B.V.

Description and critical appraisal of principal components analysis (PCA) methodology applied to pulsed-field gel electrophoresis profiles of methicillin-resistant Staphylococcus aureus isolates

Principal components analysis (PCA) has been described for over 50 years; however, it is rarely applied to the analysis of epidemiological data. In this study PCA was critically appraised in its ability to reveal relationships between pulsed-field gel electrophoresis (PFGE) profiles of methicillin- resistant Staphylococcus aureus (MRSA) in comparison to the more commonly employed cluster analysis and representation by dendrograms. The PFGE type following SmaI chromosomal digest was determined for 44 multidrug-resistant hospital-acquired methicillin-resistant S. aureus (MR-HA-MRSA) isolates, two multidrug-resistant community-acquired MRSA (MR-CA-MRSA), 50 hospital-acquired MRSA (HA-MRSA) isolates (from the University Hospital Birmingham, NHS Trust, UK) and 34 community-acquired MRSA (CA-MRSA) isolates (from general practitioners in Birmingham, UK). Strain relatedness was determined using Dice band-matching with UPGMA clustering and PCA. The results indicated that PCA revealed relationships between MRSA strains, which were more strongly correlated with known epidemiology, most likely because, unlike cluster analysis, PCA does not have the constraint of generating a hierarchic classification. In addition, PCA provides the opportunity for further analysis to identify key polymorphic bands within complex genotypic profiles, which is not always possible with dendrograms. Here we provide a detailed description of a PCA method for the analysis of PFGE profiles to complement further the epidemiological study of infectious disease. © 2005 Elsevier B.V. All rights reserved.

An appraisal of employment problems and policies at the micro-economic level

This study has concentrated on the development of an impact simulation model for use at the sub-national level. The necessity for the development of this model was demonstrated by the growth of local economic initiatives during the 1970's, and the lack of monitoring and evaluation exercise to assess their success and cost-effectiveness. The first stage of research involved the confirmation that the potential for micro-economic and spatial initiatives existed. This was done by identifying the existence of involuntary structural unemployment. The second stage examined the range of employment policy options from the macroeconomic, micro-economic and spatial perspectives, and focused on the need for evaluation of those policies. The need for spatial impact evaluation exercise in respect of other exogenous shocks, and structural changes was also recognised. The final stage involved the investigation of current techniques of evaluation and their adaptation for the purpose in hand. This led to a recognition of a gap in the armoury of techniques. The employment-dependency model has been developed to fill that gap, providing a low-budget model, capable of implementation at the small area level and generating a vast array of industrially disaggregate data, in terms of employment, employment-income, profits, value-added and gross income, related to levels of United Kingdom final demand. Thus providing scope for a variety of impact simulation exercises.

Novel hardwired distributive tactile sensing system for medical applications

This thesis described the research carried out on the development of a novel hardwired tactile sensing system tailored for the application of a next generation of surgical robotic and clinical devices, namely a steerable endoscope with tactile feedback, and a surface plate for patient posture and balance. Two case studies are examined. The first is a one-dimensional sensor for the steerable endoscope retrieving shape and ‘touch’ information. The second is a two-dimensional surface which interprets the three-dimensional motion of a contacting moving load. This research can be used to retrieve information from a distributive tactile sensing surface of a different configuration, and can interpret dynamic and static disturbances. This novel approach to sensing has the potential to discriminate contact and palpation in minimal invasive surgery (MIS) tools, and posture and balance in patients. The hardwired technology uses an embedded system based on Field Programmable Gate Arrays (FPGA) as the platform to perform the sensory signal processing part in real time. High speed robust operation is an advantage from this system leading to versatile application involving dynamic real time interpretation as described in this research. In this research the sensory signal processing uses neural networks to derive information from input pattern from the contacting surface. Three neural network architectures namely single, multiple and cascaded were introduced in an attempt to find the optimum solution for discrimination of the contacting outputs. These architectures were modelled and implemented into the FPGA. With the recent introduction of modern digital design flows and synthesis tools that essentially take a high-level sensory processing behaviour specification for a design, fast prototyping of the neural network function can be achieved easily. This thesis outlines the challenge of the implementations and verifications of the performances.

A novel actuated digit with tactile feedback for clinical applications

This thesis describes the work carried out on the development of a novel digit actuator system with tactile perception feedback to a user and demonstrated as a master-slave system. For the tactile surface of the digit, contrasting sensor elements of resistive strain gauges and optical fibre Bragg grating sensors were evaluated. A distributive tactile sensing system consisting of optimised neural networking schemes was developed, resulting in taxonomy of artificial touch. The device is suitable for use in minimal invasive surgical (MIS) procedures as a steerable tip and a digit constructed wholly from polymers makes it suitable for use in Magnetic Resonance Imaging (MRI) environments enabling active monitoring of the patient during a procedure. To provide a realistic template of the work the research responded to the needs of two contrasting procedures: palpation of the prostate and endotracheal intubation in anaesthesia where the application of touch sense can significantly assist navigation. The performance of the approach was demonstrated with an experimental digit constructed for use in the laboratory in phantom trials. The phantom unit was developed to resemble facets of the clinical applications and digit system is able to evaluate reactive force distributions acting over the surface of the digit as well as different descriptions of contact and motion relative to the surface of the lumen. Completing control of the digit is via an instrumented glove, such that the digit actuates in sympathy with finger gesture and tactile information feedback is achieved by a combination of the tactile and visual means.

Fibre Bragg grating sensors for distributive tactile sensing

Distributive tactile sensing is a method of tactile sensing in which a small number of sensors monitors the behaviour of a flexible substrate which is in contact with the object being sensed. This paper describes the first use of fibre Bragg grating sensors in such a system. Two systems are presented: the first is a one-dimensional metal strip with an array of four sensors, which is capable of detecting the magnitude and position of a contacting load. This system is favourably compared experimentally with a similar system using resistive strain gauges. The second system is a two-dimensional steel plate with nine sensors which is able to distinguish the position and shape of a contacting load, or the positions of two loads simultaneously. This system is compared with a similar system using 16 infrared displacement sensors. Each system uses neural networks to process the sensor data to give information concerning the type of contact. Issues and limitations of the systems are discussed, along with proposed solutions to some of the difficulties.

The appraisal and management of multi-storey dwelling blocks using large concrete panel systems

This exploratory study is concerned with the integrated appraisal of multi-storey dwelling blocks which incorporate large concrete panel systems (LPS). The first step was to look at U.K. multi-storey dwelling stock in general, and under the management of Birmingham City Council in particular. The information has been taken from the databases of three departments in the City of Birmingham, and rearranged in a new database using a suite of PC software called `PROXIMA' for clarity and analysis. One hundred of their stock were built large concrete panel system. Thirteen LPS blocks were chosen for the purpose of this study as case-studies depending mainly on the height and age factors of the block. A new integrated appraisal technique has been created for the LPS dwelling blocks, which takes into account the most physical and social factors affecting the condition and acceptability of these blocks. This appraisal technique is built up in a hierarchical form moving from the general approach to particular elements (a tree model). It comprises two main approaches; physical and social. In the physical approach, the building is viewed as a series of manageable elements and sub-elements to cover every single physical or environmental factor of the block, in which the condition of the block is analysed. A quality score system has been developed which depends mainly on the qualitative and quantitative conditions of each category in the appraisal tree model, and leads to physical ranking order of the study blocks. In the social appraisal approach, the residents' satisfaction and attitude toward their multi-storey dwelling block was analysed in relation to: a. biographical and housing related characteristics; and b. social, physical and environmental factors associated with this sort of dwelling, block and estate in general.The random sample consisted of 268 residents living in the 13 case study blocks. Data collected was analysed using frequency counts, percentages, means, standard deviations, Kendall's tue, r-correlation coefficients, t-test, analysis of variance (ANOVA) and multiple regression analysis. The analysis showed a marginally positive satisfaction and attitude towards living in the block. The five most significant factors associated with the residents' satisfaction and attitude in descending order were: the estate, in general; the service categories in the block, including heating system and lift services; vandalism; the neighbours; and the security system of the block. An important attribute of this method, is that it is relatively inexpensive to implement, especially when compared to alternatives adopted by some local authorities and the BRE. It is designed to save time, money and effort, to aid decision making, and to provide ranked priority to the multi-storey dwelling stock, in addition to many other advantages. A series of solution options to the problems of the block was sought for selection and testing before implementation. The traditional solutions have usually resulted in either demolition or costly physical maintenance and social improvement of the blocks. However, a new solution has now emerged, which is particularly suited to structurally sound units. The solution of `re-cycling' might incorporate the reuse of an entire block or part of it, by removing panels, slabs and so forth from the upper floors in order to reconstruct them as low-rise accommodations.

Public sector investment appraisal:the place of flexibility in the decision making process

This thesis reviews the main methodological developments in public sector investment appraisal and finds growing evidence that appraisal techniques are not fulfilling their earlier promise. It is suggested that an important reason for this failure lies in the inability of these techniques to handle uncertainty except in a highly circumscribed fashion. It is argued that a more fruitful approach is to strive for flexibility. Investment projects should be formulated with a view to making them responsive to a wide range of possible future events, rather than embodying a solution which is optimal for one configuration of circumstances only. The distinction drawn in economics between the short and the long run is used to examine the nature of flexibility. The concept of long run flexibility is applied to the pre-investment range of choice open to the decisionmaker. It is demonstrated that flexibility is reduced at a very early stage of decisionmaking by the conventional system of appraisal which evaluates only a small number of options. The pre-appraisal filtering process is considered further in relation to decisionmaking models. It is argued that for public sector projects the narrowing down of options is best understood in relation to an amended mixed scanning model which places importance on the process by which the 'national interest ' is determined. Short run flexibility deals with operational characteristics, the degree to which particular projects may respond to changing demands when the basic investment is already in place. The tension between flexibility and cost is noted. A short case study on the choice of electricity generating plant is presented. The thesis concludes with a brief examination of the approaches used by successive British governments to public sector investment, particularly in relation to the nationalised industries

Tactile sensing with fibre Bragg gratings and neural networks

Fibre Bragg grating sensors are usually expensive to interrogate, and part of this thesis describes a low cost interrogation system for a group of such devices which can be indefinitely scaled up for larger numbers of sensors without requiring an increasingly broadband light source. It incorporates inherent temperature correction and also uses fewer photodiodes than the number or sensors it interrogates, using neural networks to interpret the photodiode data. A novel sensing arrangement using an FBG grating encapsulated in a silicone polymer is presented. This sensor is capable of distinguishing between different surface profiles with ridges 0.5 to 1mm deep and 2mm pitch and either triangular, semicircular or square in profile. Early experiments using neural networks to distinguish between these profiles are also presented. The potential applications for tactile sensing systems incorporating fibre Bragg gratings and neural networks are explored.

Investement appraisal in a deregulated electricity market

This thesis analyses the impact of deregulation on the theory and practice of investment decision making in the electricity sector and appraises the likely effects on its long term future inefficiency. Part I describes the market and its shortcomings in promoting an optimal generation margin and plant mix and in reducing prices through competition. A full size operational model is developed to simulate hour by hour operation of the market and analyse its features. A relationship is established between the SMP and plant mix and between the LOLP and plant margin and it is shown bow a theoretical optimum can be derived when the combined LOLP payments and the capital costs of additional generation reach a minimum. A comparison of prices against an idealised bulk supply tariff is used to show how energy prices have risen some 12% in excess of what might have occurred under the CEGB regime. This part concludes with proposals to improve the marlappraisal is no longer valid and develops a new approach. It is shown how an individual generator can predict his utilisation and income to establish the worth of investment and demonstrates the validity of the operational model proposed. An empirical relationship is developed between profit and capacity and this is used to develop the theory to illustrate how companies interact. 1bree different economic models are developed to represent different market conditions and these are tested against the actual investment decisions since deregulation to demonstrate their appropriateness. It is shown that the current market mechanisms could lead to suboptimal investment. Part 3 discusses the essential role of transmission in enabling competition and reviews worldwide practices illustrating little consensus on charging for its use. Basic costing principles are described and a new model is developed to demonstrate bow a generator may strike supply agreements either side of an interconnector to influence prices so as to maximise his income. The optimal pricing strategy for the transmitter is also derived and consumer response is simulated .The concept of transmission uplift is developed and the operational model is extended to include transmission constraints and then used to establish monthly incremental transmission constraint cost functions. It is shown how these can be used to appraise investment options and optimally plan outages. Part 4 concludes by discussing the regulatory framework and its limitations in improving efficiency or encouraging the optimum levels of investment. The principal findings of the thesis are reviewed and potential market improvement are described. This part concludes with a discussion of alternative market structures and likely future developments.

Distributive tactile sensing using fibre Bragg grating sensors

Two distributive tactile sensing systems are presented, based on fibre Bragg grating sensors. The first is a onedimensional metal strip with an array of 4 sensors, which is capable of detecting the magnitude and position of a contacting load. This system is compared experimentally with a similar system using resistive strain gauges. The second is a two-dimensional steel plate with 9 sensors which is able to distinguish the position and shape of a contacting load. This system is compared with a similar system using 16 infrared displacement sensors. Each system uses neural networks to process the sensor data to give information concerning the type of contact.

Appraisal of the Karnalí Employment Programme as a regional social protection scheme

The Karnali Employment Programme (KEP) is a public works based social protection scheme in one of the poorest parts of Nepal attempting to address the regional dimension of poverty and vulnerability.