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This thesis, awarded by published work represents a collection of clinical studies that advance the knowledge of why to, and how best to, administer propofol safely using an innovative technique, 'Patient Maintained Sedation' (PMS).

This research explores the managerial problems associated with adoption of business to business (B2B) enterprise integration in the UK engineer to order (ETO) manufacturing sector. Its aim is to develop a B2B enterprise integration hierarchy to overcome managerial problems and propose a model for implementation. The first part of the research developed an overview of the evolution of the B2B enterprise integration concept, a definition, perceived business benefits and its general status in the UK manufacturing sector. The research is grounded in the extant literature covering supply chain integration, information technology acceptance literature, crisis management and implementation success factors. A qualitative case study approach was selected comprising two phases. The first phase involved key informant interviews at eleven ETO companies in the UK. Three interviews with key informants were carried out at each company. This group triangulation approach mitigated any bias. Four managerial problems were identified: management awareness of the benefits and implementation challenges, risk in terms of return on investment and business continuity during implementation, information security risk associated with loss of competitive advantage and lack of relevant skills within the organisation. From these findings, a B2B de-coupled integration hierarchy was developed and an implementation model proposed. The second phase involved an in case participatory action research study over a one year budget cycle at one of the eleven companies during implementation of a B2B system. This case study tested the use of a B2B de-coupled integration hierarchy approach and refined the proposed implementation model. The outcome of the research recommends a B2B de-coupled integration hierarchy and an iterative implementation model for overcoming the four key inhibitors identified. This is significant for practitioners, particularly in the ETO sector, who are in the process of implementing B2B enterprise integration systems. It confirms that successful implementation can be achieved if senior management teams are fully aware of the potential benefits and the implementation challenges. Additionally, business and information security risks must be dealt with by appropriate de-coupling and the workforce should have the relevant skills to deal with the new systems. From an academic perspective, this research provides two significant contributions. This is the first study to explore the managerial problems associated with adoption of B2B enterprise integration by using a combination of interviewing key informants within an organisational setting and a participatory action case study. Furthermore, it is the first study to propose an iterative implementation model to overcome managerial problems associated with adoption of B2B enterprise integration in the UK ETO sector. It should be noted that this research is limited to key informant interviews at eleven companies and one case study. In order to provide unequivocal validation and generalisability, the research should be expanded to cover other manufacturing sectors.

The augmentation of navigation systems with landmarks has been proposed as a method of improving the effectiveness of the technology, and facilitating drivers' engagement with the environment. As a consequence, benefits are predicted both in increased spatial learning and reduced driver distraction. Good navigational landmarks are however both laborious to collect and difficult to define. Collecting useful data as a by-product of mobile applications or games has received growing research interest. It has been suggested as a way of collecting location based data, which may be reused in navigation systems or other applications. Previous research games, with the aim of collecting landmarks, have encountered problems with producing a game concept which encourages the collection of good navigational landmarks. Past research has also concentrated on pedestrian applications. Since the majority of navigation applications are used in cars, exploring the potential of capturing data in the context of a car journey makes a novel and valuable contribution. This research aimed to devise a game concept, which could be played by passengers in cars and would collect useful landmark data as a by-product. The thesis describes how a virtual graffiti concept was generated, and how it was evaluated in both simulated and real world journeys. Design studies, using video journeys, were performed to gather information and to inform the development of a high level concept. An in-car trial of a prototype, which embodied a virtual graffiti game mechanic, was carried out, and 38 participants took part. The data collected in this trial was then evaluated by means of a survey, in which 100 respondents assessed the quality of the landmarks collected and their potential for reuse in navigation applications. Players of the virtual graffiti prototype displayed a consensus in where to place their graffiti tags. In ten out of twelve locations, over 30% of the players chose the same object to tag. Furthermore, a significant correlation was found between how highly landmarks were rated in the survey and how frequently they were tagged in the car trial. This work demonstrates a method for evaluating a crowdsourcing application for car journeys, and proposes an effective strategy of designing games with by-products, which is to relate the role of the objects used in the game to the purpose of the by-products. In the case of a virtual graffiti game the two are related by environmental salience. Objects were chosen by the graffiti taggers because of features such as size, visibility, ease of description and semantic salience, and these factors are also defining characteristics of good navigational landmarks. The studies described in this thesis provide evidence that crowdsourcing to collect landmarks will not require large numbers of people, or extensive coverage of an area, to produce candidate landmarks for navigation. The thesis also presents some practical ideas for the use of the by-products of landmark capturing games in navigation systems, and some implications for the design of car-based, virtual graffiti games and car-based crowdsourcing in general.

Tropical soils are often characterised by low phosphorus availability prompting the view that the productivity of many tropical forests may be phosphorus (P) rather than nitrogen (N) limited. Nevertheless, to date, no study has assessed the mechanisms by which P-deficiency might be limiting rates of photosynthesis in tropical trees. A controlled glasshouse experiment investigated the effect of P deficiency on rates of photosynthesis (A) and related leaf traits for seven Australian tropical tree species drawn from different plant functional types (pFTs) thought to differ in their photosynthesis/nutrient relationships. Measurements of gas exchange and leaf structure were combined with laboratory assays ofleaf nutrients; subsequent field campaigns were conducted in tropical Queensland (also comparing forest with savanna), Peru and French Guiana. The greenhouse results showed that the A- [N] relationship is affected by P supply, but PFT effects were not as predicted and in Queensland savanna species were found to have higher photosynthetic N use efficiency compared with forest trees - despite lower leaf [P]. In South America, an expected cross-basin gradient in P availability was' confirmed with higher [P] for the Peruvian trees, but Ama.'{ did not differ between the two Peruvian plots despite a 48% increase in mean [P]. The combined field dataset, including more than 80 species, allowed novel cross-continental comparisons of major leaf fractions of P and N - these were found to differ at each hierarchical level: country, site and species. Attempts to define a unifying photosynthetic model for tropical trees confirmed a dominant role for N, but with a critical role for P also invoked. Model performance was, however, improved by allowing for specific geographic and phylogenetic effects. A current lack of understanding as to the basis of these unexplained phytogeograhic effects on photosynthesis/nutrient relationships constitutes a major obstacle in the development of universally-applicable large-scale photosynthesis models.

This thesis addresses how and when British pharmaceutical firms first manufactured synthetic drugs, and how they persuaded doctors to test novel therapies in clinical trials. Edwardian Britain was reliant on Germany for synthetic drugs, so how did British firms meet this challenge in the First World War, and how was this new form of the British pharmaceutical industry nurtured in the interwar period? Previous studies have covered the industry's origins in pharmacy roots and dyestuffs, and the growth of the American indUStry, but without an overall synthesis. There are several good company histories for Britain, and Robson and Quirke compared pharmaceuticals in France and Britain, whilst Tansey examined physiological research at Burroughs Wellcome; but little has appeared on chemical research and synthetic manufacture. I will emphasise the work of Francis Carr who developed synthetic drugs at Burroughs Wellcome, Boots and British Drug Houses. As for testing, the literature covers early statistics and the clinical trials of major biological drugs such as insulin; but these did not originate with industry. With synthetic and other novel drugs, as I show, firms found it difficult to arrange clinical trials and they turned to the MRC for assistance. I examine these negotiations and trials in some detail. 9 Chapter 1 reviews the historiography ofthe pharmaceutical industry and the clinical testing of drugs. Chapter 2 examines the varied origins of the industry, contrasting ethical and patent medicines, and comparing Britain with Germany and America. Chapter 3 shows how Burroughs Wellcome combined novel drugs in sophisticated dosage forms, adopting new sales strategies and establishing laboratories to standardise drugs. Their experience in small scale synthesis from 1896 enabled them to prepare German drugs when patents were abrogated in the First World War (chapter 4). The MRC and other firms poached Burroughs Well come researchers, and the MRC took standardisation as a central theme, so establishing an international reputation. Chapter 5 addresses the postwar campaigns for tariff protection, and the extension ofMRC drug evaluations as British firms strove to remain competitive. Novel vitamin and hormonal drugs allowed them to expand their manufacturing capacity while gaining further experience of drug synthesis. Chapter 6 describes how British firms campaigned for clinical testing of drugs from 1922 -1930 and explains why a Therapeutic Trials Committee (TTC) was established in 1931. Chapter 7 examines the strategy of Burroughs Wellcome post-war, by analysing the strategic debates within their Scientific and Technical Committee. Chapter 8 examines the TTC, how they favoured British drugs, and how studies complemented their own research interests; it provides insight into the research strategies of British (and foreign) firms, plus an assessment of the TTC as seen by the MRC and by companies. Chapter 9 offers general conclusions and contrasts the position of British manufacturers at the outbreak of the Second World War with their position at the outbreak of the Great War in August 1914. Some opportunities for further work are then identified.