Increased potential of a cationic liposome-based delivery system:enhancing stability and sustained immunological activity in pre-clinical development

The combination of dimethyl dioctadecyl ammonium bromide (DDA) and the synthetic cord factor trehalose dibehenate (TDB) with Ag85B-ESAT-6 (H1 fusion protein) has been found to promote strong protective immune responses against Mycobacterium tuberculosis. The development of a vaccine formulation that is able to facilitate the requirements of sterility, stability and generation of a vaccine product with acceptable composition, shelf-life and safety profile may necessitate selected alterations in vaccine formulation. This study describes the implementation of a sterilisation protocol and the use of selected lyoprotective agents in order to fulfil these requirements. Concomitantly, close analysis of any alteration in physico-chemical characteristics and parameters of immunogenicity have been examined for this promising DDA liposome-based tuberculosis vaccine. The study addresses the extensive guidelines on parameters for non-clinical assessment, suitable for liposomal vaccines and other vaccine delivery systems issued by the World Health Organisation (WHO) and the European Medicines Agency (EMEA). Physical and chemical stability was observed following alteration in formulations to include novel cryoprotectants and radiation sterilisation. Immunogenicity was maintained following these alterations and even improved by modification with lysine as the cryoprotective agent for sterilised formulations. Taken together, these results outline the successful alteration to a liposomal vaccine, representing improved formulations by rational modification, whilst maintaining biological activity.

An expert system for the development of a health and safety policy/risk assessment in the plastics industry

Health and safety policies may be regarded as the cornerstone for positive prevention of occupational accidents and diseases. The Health and Safety at Work, etc Act 1974 makes it a legal duty for employers to prepare and revise a written statement of a general policy with respect to the health and safety at work of employees as well as the organisation and arrangements for carrying out that policy. Despite their importance and the legal equipment to prepare them, health and safety policies have been found, in a large number of plastics processing companies (particularly small companies), to be poorly prepared, inadequately implemented and monitored. An important cause of these inadequacies is the lack of necessary health and safety knowledge and expertise to prepare, implement and monitor policies. One possible way of remedying this problem is to investigate the feasibility of using computers to develop expert system programs to simulate the health and safety (HS) experts' task of preparing the policies and assisting companies implement and monitor them. Such programs use artificial intelligence (AI) techniques to solve this sort of problems which are heuristic in nature and require symbolic reasoning. Expert systems have been used successfully in a variety of fields such as medicine and engineering. An important phase in the feasibility of development of such systems is the engineering of knowledge which consists of identifying the knowledge required, eliciting, structuring and representing it in an appropriate computer programming language.

A composite framework for the strategic alignment of information systems development

Information systems are corporate resources, therefore information systems development must be aligned with corporate strategy. This thesis proposes that effective strategic alignment of information systems requires information systems development, information systems planning and strategic management to be united. Literature in these areas is examined, breaching the academic boundaries which separate these areas, to contribute a synthesised approach to the strategic alignment of information systems development. Previous work in information systems planning has extended information systems development techniques, such as data modelling, into strategic planning activities, neglecting techniques of strategic management. Examination of strategic management in this thesis, identifies parallel trends in strategic management and information systems development; the premises of the learning school of strategic management are similar to those of soft systems approaches to information systems development. It is therefore proposed that strategic management can be supported by a soft systems approach. Strategic management tools and techniques frame individual views of a strategic situation; soft systems approaches can integrate these diverse views to explore the internal and external environments of an organisation. The information derived from strategic analysis justifies the need for an information system and provides a starting point for information systems development. This is demonstrated by a composite framework which enables each information system to be justified according to its direct contribution to corporate strategy. The proposed framework was developed through action research conducted in a number of organisations of varying types. This suggests that the framework can be widely used to support the strategic alignment of information systems development, thereby contributing to organisational success.

The development of a market orientation in a turbulent, transitional environment:the case of Ukraine

This research is concerned with the case of Ukraine where there has been a fundamental change in the economic environment engendered by the transition from a centrally planned to a market economy and the resulting conditions of economic crisis. The way that Ukrainian marketers and consumers are reacting to this environmental change is the principal concern of the research together with the basic linkages between critical environmental elements and strategic marketing decisions. This research analyses the way in which marketing evolves in a turbulent, transitional environment. The study is based on eight case analyses within the retail sector of the Ukrainian market. The process of transition to a free market economy leads a researcher to question the validity of existing theories that have been based on empirical data that has been collected in the stable marketing environment of the West. For this reason an in-depth, theory building methodology is preferred. A number of broad research objectives were set. Firstly, to establish whether the sales - production - marketing stages model of marketing evolution, derived from empirical data collected in stable Western environments, is relevant in the context of the turbulent, transitional environment of Ukraine. Secondly, to establish if, in this turbulent, transitional environment, idiosyncratic approaches to marketing are emerging and thirdly to assess the development of attitudes to marketing, organisation for marketing and the development of marketing strategy in Ukraine. The main conclusions of this thesis are firstly, that the stages model of marketing orientation is not relevant in the context of Ukraine, secondly that there are idiosyncratic approaches to marketing emerging in the turbulent, transitional environment of Ukraine and finally that the above developments have a profound impact on the development of attitudes to marketing, organisation for marketing and the development of marketing strategy in Ukraine.

A survey of some small firms in the rural areas of England: their structure and functions, with special reference to factors that affect their development

This study was concerned with the structure, functions and development, especially the performance, of some rural small firms associated with the Council for Small Industries in Rural Areas (C?SIRA) of England. Forty firms were used as the main basis of analysis. For some aspects of the investigation, however, data from another 54 firms, obtained indirectly through nine CoSIRA Organisers, were also used. For performance-analysis, the 40 firms were firstly ranked according to their growth and profitability rates which were calculated from their financial data. Then each of the variables hypothesised to be related to performance was tested to ascertain its relationship with performance, using the Spearman's Rank Correlation technique. The analysis indicated that each of the four factors .. the principal, the firm itself, its management, and the environment - had a bearing upon the performance of the firm. Within the first factor, the owner-manager's background and attitudes were found to be most important; in the second, the firm's size, age and scope of activities were also found to be correlated with performance; with respect to the third, it was revealed that firms which practised some forms of systems in planning, control and costing performed better than those which did not and, finally with respect to the fourth factor, it was found that some of the services provided by CoSIRA, especially credit finance, were facilitative to the firm's performance. Another significant facet of the firms highlighted by the study was their multifarious roles. These, meeting economic, psychological, sociological and political needs, were considered to be most useful to man and his society. Finally, the study has added light to the structural characteristics of the sampled firms, including various aspects of their development, orientation and organisation, as well as their various structural strengths and weakness. ' .

Development and application of magnetoencephalographic methods in the investigation of the human visual system

This thesis is an exploration of the organisation and functioning of the human visual system using the non-invasive functional imaging modality magnetoencephalography (MEG). Chapters one and two provide an introduction to the ‘human visual system and magnetoencephalographic methodologies. These chapters subsequently describe the methods by which MEG can be used to measure neuronal activity from the visual cortex. Chapter three describes the development and implementation of novel analytical tools; including beamforming based analyses, spectrographic movies and an optimisation of group imaging methods. Chapter four focuses on the use of established and contemporary analytical tools in the investigation of visual function. This is initiated with an investigation of visually evoked and induced responses; covering visual evoked potentials (VEPs) and event related synchronisation/desynchronisation (ERS/ERD). Chapter five describes the employment of novel methods in the investigation of cortical contrast response and demonstrates distinct contrast response functions in striate and extra-striate regions of visual cortex. Chapter six use synthetic aperture magnetometry (SAM) to investigate the phenomena of visual cortical gamma oscillations in response to various visual stimuli; concluding that pattern is central to its generation and that it increases in amplitude linearly as a function of stimulus contrast, consistent with results from invasive electrode studies in the macaque monkey. Chapter seven describes the use of driven visual stimuli and tuned SAM methods in a pilot study of retinotopic mapping using MEG; finding that activity in the primary visual cortex can be distinguished in four quadrants and two eccentricities of the visual field. Chapter eight is a novel implementation of the SAM beamforming method in the investigation of a subject with migraine visual aura; the method reveals desynchronisation of the alpha and gamma frequency bands in occipital and temporal regions contralateral to observed visual abnormalities. The final chapter is a summary of main conclusions and suggested further work.

Manufacturing organisation in developing countries with particular reference to Iraq

Industrially developed countries are able to absorb modern techniques of science and technology quite readily; this is not the case for less-developed countries. Attempts made by developing countries have been ineffective due to factors not readily admitted. This thesis highlights the areas that need to be developed by under-developed countries, and covers economic, scientific and technological, and social aspects as well as technology transfer. Economic areas considered acknowledge that within any one country there should be proper procedures for planning economic and industrial projects (plant design) supported by efficient economic development strategy. Scientific and technological factors considered include the major areas that need to be developed in order to produce and/or deal with scientific and technological issues for the interest of the national development. Technology transfer areas considered include the necessity of building up a national body (system) responsible for dealing with activities and tasks of transferring foreign-made technology so that it can be employed effectively within the environment of the country. Social factors considered include the need to develop human resources which can be employed efficiently into the whole process of development, and particularly for the above proposed systems. Education and training are the major elements that ought to be tackled to produce skilled manpower and to overcome the social and cultural values and traditions that are inherited by the society. This thesis highlights the above areas in an attempt to plan and organise the development of science and technology, and their implementation into the development as a whole. Whilst recognising the problems of creating this sort of development in developing countries, the author considers the benefits to be obtained are much greater in the long run.

The evaluation and development of the lead authority partnership scheme as a central intervention strategy for health and safety enforcement by local authorities

The research comprises a suite of studies that examines and develops the Lead Authority Partnership Scheme (LAPS) as a central intervention strategy for health and safety by local authority (LA) enforcers. Partnership working is a regulatory concept that in recent years has become more popular but there has been little research conducted to investigate, explore and evaluate its practical application. The study reviewed two contrasting approaches to partnership working between LAs and businesses, both of which were intended to secure improvements in the consistency of enforcement by the regulators and in the health and safety management systems of the participating businesses. The first was a well-established and highly prescriptive approach that required a substantial resource commitment on the part of the LA responsible for conducting a safety management review (SMR) of the business. As a result of his evaluation of the existing ‘full SMR’ scheme, the author developed a second, more flexible approach to partnership working. The research framework was based upon a primarily qualitative methodology intended to investigate and explore the impact of the new flexible arrangements for partnership working. The findings from this study of the flexible development of the scheme were compared and contrasted with those from studies of the established ‘full SMR’ scheme. A substantial degree of triangulation was applied in an attempt to strengthen validity and broaden applicability of the research findings. Key informant interviews, participant observation, document/archive reviews, questionnaires and surveys all their particular part to play in the overall study. The findings from this research revealed that LAPS failed to deliver consistency of LA enforcement across multiple-outlet businesses and the LA enforced business sectors. Improvement was however apparent in the safety management systems of the businesses participating in LAPS. Trust between LA inspector and safety professional was key to the success of the partnerships as was the commitment of these key individuals. Competition for precious LA resources, the priority afforded to food safety over health and safety, the perceived high resource demands of LAPS, and the structure and culture of LAs were identified as significant barriers to LA participation. Flexible approaches, whilst addressing the resource issues, introduced some fresh concerns relating to credibility and delivery. Over and above the stated aims of the scheme, LAs and businesses had their own reasons for participation, notably the personal development of individuals and kudos for the organisation. The research has explored the wider implications for partnership working with the overall conclusion it is most appropriately seen as a strategic level element within a broader structured intervention strategy.

The development and operation of the effective interpersonal relationship skills relevant to career development problems from staff assessment at an industrial research laboratory

This study concerns the application of a model of effective interpersonal relationships to problems arising from staff assessment at I.C.I. Ltd. Corporate Laboratory between 1972 and 1974. In collaboration with academic and industrial supervision, the study commenced with a survey of management and supervisor opinions about the effectiveness of current staff (work) relationships, with particular reference to the problem of recognising and developing creative potential. This survey emphasised a need to improve the relationships between staff in the staff assessment context. A survey of research into creativity emphasised the importance of the interpersonal environment for obtaining creative behaviour in an organisation context. A further survey of theories of how inter­personal behaviour related to personal creativity (therapeutic psychology) provided a model of effective interpersonal behaviour (Carkhuff, 1969) that could be applied to the organisation context of staff assessment. The objective of the project was redefined as a need to improve the conditions of interpersonal behaviour in relation to certain (career development) problems arising from staff assessment practices. In order to demonstrate the application of the model of effective interpersonal behaviour, the research student recorded interviews between himself and members of staff designed to develop and operate the dimensions of the model. Different samples of staff were used to develop the 'facilitative' and the 'action oriented' dimensions of bahaviour, and then for the operation of a helping programme (based on vocational guidance tests). These interactions have been analysed, according to the scales of measurement in the model ana the results are presented in case study form in this thesis. At each stage of the project, results and conclusions were presented to the sponsoring organisation (e.g. industrial supervisor) in order to assess their (subjective) opinion of relevance to the organ­ isation. Finally, recommendations on further actions towards general improvement of the work relationships in the laboratory were presented in a brief report to the sponsor.

Industrial new product planning:a study of the sources of new product ideas and the development of new product proposals in the UK computer industry

This thesis presents a study of the sources of new product ideas and the development of new product proposals in an organisation in the UK Computer Industry. The thesis extends the work of von Hippel by showing how the phenomenon which he describes as "the Customer Active Paradigm for new product idea generation" can be observed to operate in this Industry. Furthermore, this thesis contrasts his Customer Active Paradigm with the more usually encountered Manufacturer Active Paradigm. In a second area, the thesis draws a number of conclusions relating to methods of market research, confirming existing observations and demonstrating the suitability of flexible interview strategies in certain circumstances. The thesis goes on to demonstrate the importance of free information flow within the organisation, making it more likely that sought and unsought opportunities can be exploited. It is shown that formal information flows and documents are a necessary but not sufficient means of influencing the formation of the organisation's dominant ideas on new product areas. The findings also link the work of Tushman and Katz on the role of "Gatekeepers" with the work of von Hippel by showing that the role of gatekeeper is particularly appropriate and useful to an organisation changing from Customer Active to Manufacturer Active methods of idea generation. Finally, the thesis provides conclusions relating to the exploitation of specific new product opportunities facing the sponsoring organisation.

Action research in a collective organisation:Developing an education programme in a pressure group

The aim of this project was to develop the education work of an environmental pressure group. The research devised and implemented a project to produce multi-media teaching packs on the urban environment. Whilst this involved understanding environmental education it was necessary to research beyond this to include the various structural and dynamic constraints on change in the field. This presented a number of methodological difficulties; from the resolution of which a model of the research process involved in this project has been developed. It is argued that research oriented towards practical change requires the insights of an experienced practitioner to be combined with the rigours of controlled systematic enquiry. Together these function as a model-building process encompassing intuition, induction and deduction. Model testing is carried out through repeated intervention in the field; thus an interplay between researcher and client ensues such that the project develops in a mutually acceptable direction. In practice, this development will be both unpredictable and erratic. Although the conclusions reached here are based on a single case study they address general methodological issues likely to be encountered in different field settings concerned with different practical problems.

A rule based model for the objective determination of the e-business requirements of a manufacturing organisation

The starting point of this research was the belief that manufacturing and similar industries need help with the concept of e-business, especially in assessing the relevance of possible e-business initiatives. The research hypotheses was that it should be possible to produce a systematic model that defines, at a useful level of detail, the probable e-business requirements of an organisation based on objective criteria with an accuracy of 85%-90%. This thesis describes the development and validation of such a model. A preliminary model was developed from a variety of sources, including a survey of current and planned e-business activity and representative examples of e-business material produced by e-business solution providers. The model was subject to a process of testing and refinement based on recursive case studies, with controls over the improving accuracy and stability of the model. Useful conclusions were also possible as to the relevance of e-business functions to the case study participants themselves. Techniques were evolved to synthesise the e-business requirements of an organisation and present them at a management summary level of detail. The results of applying these techniques to all the case studies used in this research were discussed. The conclusion of the research was that the case study methodology employed was successful. A model was achieved suitable for practical application in a manufacturing organisation requiring help with a requirements definition process.

An investigation of the prevalence and measurement of teams in organisations:the development and validation of the real team scale

This thesis begins with a review of the literature on team-based working in organisations, highlighting the variations in research findings, and the need for greater precision in our measurement of teams. It continues with an illustration of the nature and prevalence of real and pseudo team-based working, by presenting results from a large sample of secondary data from the UK National Health Service. Results demonstrate that ‘real teams’ have an important and significant impact on the reduction of many work-related safety outcomes. Based on both theoretical and methodological limitations of existing approaches, the thesis moves on to provide a clarification and extension of the ‘real team’ construct, demarcating this from other (pseudo-like) team typologies on a sliding scale, rather than a simple dichotomy. A conceptual model for defining real teams is presented, providing a theoretical basis for the development of a scale on which teams can be measured for varying extents of ‘realness’. A new twelve-item scale is developed and tested with three samples of data comprising 53 undergraduate teams, 52 postgraduate teams, and 63 public sector teams from a large UK organisation. Evidence for the content, construct and criterion-related validity of the real team scale is examined over seven separate validation studies. Theoretical, methodological and practical implications of the real team scale are then discussed.

Opportunity, fair process and relationship value:career development as a driver of proactive work behaviour

In line with recent findings from organisational justice theory, we hypothesised that employee proactive behaviour and careerist orientation is predicted by the interplay of perceived favourability of career development opportunities, the perceived fairness of the procedures used to decide them, and employee organisational commitment. Employees (N = 325) of a large financial services organisation responded to a self-completion questionnaire. As predicted, when career development opportunities were viewed unfavourably, perceived procedural justice was significantly and positively related to individual proactive behaviour and significantly and negatively related to careerist orientation but only when organisational commitment was high. It appears that high procedural justice may only 'offset' the negative effects of unfavourable career development opportunities when employees identify with, and are committed to, their organisation. Further support is presented for a relational, rather than instrumental, model of procedural justice when reflecting on employee reactions to their employers' policies and decision-making. Implications for theory and practice are discussed.