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Softer forms of systems thinking and Soft-OR (Operational Research) provide the theory, the methodology and the methods by which managers can see the situations they are trying to manage as wholes. They facilitate what has become known as "bigger picture" thinking and are widely acknowledged as effective ways to manage complexity. But despite nearly 50 years of development, the extent to which these ideas have penetrated mainstream management thinking and practice is very limited. Existing research suggests that adoption of systemic problem structuring methods (systemic PSMs) is frustrated by a number of factors. But questions about the take-up of systemic PSMs remain under-theorised. This thesis aims to deepen our understanding of how managers receive and take-up, and sometimes repudiate, systemic PSMs. It uses a qualitative multiple case study design to report findings from four interventions using systemic PSMs in four organisations (two from the UK and two from Romania). The findings are interpreted through the lens of Luhmann's complex social systems theory. Applications of softer forms of systems thinking are better received and are more likely to be taken-up in situations where an existing organisational decision premise is contested and no longer functions as a stable reference point for future decisions. In these circumstances, managers show greater curiosity in systemic PSMs and are more willing to adopt them to generate new "ways of seeing". However, they also present managers with a paradox. Used as a means to explore an organisation's future, and as a means of deciding what that future could be, managers are more reluctant to perform "bigger picture" analyses if the product of such thinking is perceived to over-specify plans for the future; plans which might well turn out to be ill-adapted to a "future" that is fundamentally unknown. This changes the way we think about interventions using systemic PSMs and leads to a theory that produces a more nuanced understanding of the circumstances in which they might be needed and effectively deployed. Existing theory tends to focus on ideal-type problem contexts. But the near-manifestation of such contexts in actual practice does not automatically guarantee that systems-inquiring methods will be taken-up, for existing theory underplays the inherent decision logic of the organisation in which the intervention takes place and underestimates the organisation's ability to create its own "secondary complexity". Systemic PSMs are more likely to be in demand when existing "ways of seeing" have been exhausted.

The use of biomacromolecules, e.g. peptides and antibodies, as therapeutics, so-called ‘biologics’, is experiencing an increase in interest as more and more small molecule therapeutics fail to meet the regulatory requirements for human use. To expedite the examination of such biologics as useful therapeutics, positron-emission tomography (PET) is being used as an early stage non-invasive in vivo imaging modality to rule in, or to rule out, candidates from the drug discovery pipeline. To realise this goal, small, reactive radiolabelled compounds, termed prosthetic groups, are often used to label the biologic of interest. Furthermore, prosthetic groups may also be incorporated into small molecule therapeutics, thus enabling rapid elucidation of candidates in a pre-clinical environment from a single appropriate prosthetic group precursor/apparatus set up. Diaryliodonium salts have been considered as useful precursors to prosthetic groups, as this class of compound may facilitate the one-step introduction of a nucleophilic radiolabel, e.g. [18F]fluoride ion, onto any position of a given arene. However, direction of the radiolabel onto the target arene is generally dictated by stereoelectronics, where the nucleophile is substituted upon the least electron-rich arene. To achieve this effect, electron-rich arenes, such as 2-thienyl, are employed. However, a potentiated product where the second arene is also electron-rich is the poorly characterised 2-[18F]fluorothiophene. To ensure that the products of radiofluorination processes reported herein are correctly assigned, an authentic sample of 2-[19F]fluorothiophene has been prepared on a 750 mmol scale (Scheme A). Scheme A: Synthesis of 2-[19F]fluorothiophene. Unambiguous verification of the detection of 2-[18F]fluorothiophene has herein been achieved for the first time by radiofluorination of the highly electrophilic electron-rich dithienyliodonium trifluoroacetate, using a microfluidic apparatus. iii Microfluidic apparatus is a technology which is experiencing an emergence as a useful means of probing the conditions advantageous to the production of radiolabeled material. We investigated the use of such apparatus in the optimised preparation of regioisomers of a key prosthetic group, [18F]fluorobenzaldehyde ([18F]FBA). The successful optimisation of the radiolabeling process has delivered 4-[18F]FBA in excellent radiochemical yields (>95%), as well delivering the associated regioisomer, 3-[18F]FBA, which is unavailable by convention means, by use of diaryliodonium salt precursors (Scheme B). Scheme B: Radiosynthesis of 4-[18F]FBA and 3-[18F]FBA from diaryliodonium salt precursors. Another prosthetic group considered bears the thiol reactive maleimide. An appropriate synthesis of a suitable diaryliodonium salt precursor (Scheme C) is reported herein. Scheme C: Synthesis of the precursor to the prosthetic group N-(4-[18F]fluorophenyl)maleimide.

This thesis investigates technological evolution in bloomery iron production. Patterns of variation in archaeological, historical, and metallurgical data on early ironworking systems are tracked across space-time and explained in terms of evolutionary processes. While some patterns may be attributable to localised resource constraints, others may be explained by the differential success of technological variants in ever-changing socioeconomic environments. Models derived from neo-Darwinian theory are constructed to identify lineages of technological knowledge from the bulk chemistries of ironworking residues, especially slag. Lineages are then explained in terms of evolutionary sorting processes. In order to minimise the effects of resource constraints, case studies are drawn from a single geographic region northwest Wales. Study sites include: Crawcwellt West (300 BC to AD 50), Bryn y Castell (150 BC to AD 250), and Llwyn Du (AD 1357 to AD 1450). While neither complete nor continuous in their temporal coverage, these sites offer a basis for examining evolutionary processes at different scales and in different socioeconomic settings. Bulk chemistries of slag, ore, and furnace materials are determined by polarising energy dispersive x-ray fluorescence spectrometry (P)ED-XRF. These data are supplemented with reflected-light microscopy of smelting slag. Both archaeological and experimentally derived materials were analyzed. The experimental data provides technological insights and a controlled means of evaluating analytical models. Historical data are used to model socioeconomic conditions. Results stress the importance of analyzing variation in early ironworking technology. Considerable variation is observed in slag chemistry between the Iron Age and medieval sites and between activity phases of the same site. The later phases of Llwyn Du contain coexisting chemical groups suggesting the coordinated use of multiple ironmaking recipes. Adaptive processes account for most of the observed patterns of variation building optimal recipes and strategies for fluctuating environments. Specific technological trajectories are historically contingent and geologically constrained.

A theoretical study of steroidal inhibitors of the enzymes Glucose-6-Phosphate Dehydrogenase and Aromatase is presented. Both enzyme systems are of interest in the study of cancer, the latter being the final step in the biosynthesis of oestrogens which are involved in certain types of breast cancer. Two levels of theory are employed in the study, namely, Ab Initio and Semi Empirical methods. Structures and charges have been calculated using the MOPAC and GAUSSIAN programs and these have been used to model the efficacy of various inhibitors. The major tool in comparing these steroids has been the molecular electrostatic potential (MEP). Maps of the MEP and an analysis of the similarity between the MEP s of different molecules have led both to a method of assessing the activities of steroids as enzyme inhibitors and requirements for the electronic structure of the steroid binding sites within these enzymes. A molecular graphics display program has been developed to facilitate this work. It has been designed to make full use of the facilities available. The quality of the resulting display has improved greatly on what was previously available and has been of value in studies of large molecular systems. The program is written in VAX FORTRAN and uses the Graphics Kernel System (GKS) to produce graphical output and should be reasonably easy to transfer to other systems. Finally, to determine whether PM3 really is a significant advance on AM1, a comparison of the two semi empirical methods is presented. The calculated properties of steroid hormones are compared to those of both Ab Initio calculations and experimental determinations, allowing the quality of the semi empirical predictions to be assessed.

Low energy positron clouds from a buer gas trap have been characterised and compressed by a novel double rotating wall (RW) electric field. A theoretical and experimental study comparing compression due to dipolar single and double RW electric fields is presented, with details of a custom-built function generator capable of operating on two sets of four, six, and eight-segment electrodes. The installation of a cylindrical Penning trap with two sets of six-segment RW elec-trodes has allowed the implementation of a double RW, which provides a better approximation to the electric potential in the model for independent charged par-ticle compression. A reduction in particle heating has been observed with the double RW, whilst obtaining at least equivalent compression as the single RW, which may in future allow a reduction in the minimum attainable cloud width. Without the use of RW electric fields, optimisations to positron ejection and recapture techniques led to positron clouds being held in a deep, harmonic poten-tial well for over 100 s, enabling time to study RW electric fields and to perform resistive cooling experiments.

Antihydrogen, the simplest pure-antimatter atomic system, holds the promise of direct tests of matter-antimatter equivalence and CPT invariance, two of the outstanding unanswered questions in modern physics. Antihydrogen is now routinely produced in charged-particle traps through the combination of plasmas of antiprotons and positrons, but the atoms escape and are destroyed in a minuscule fraction of a second. The focus of this work is the production of a sample of cold antihydrogen atoms in a magnetic atom trap. This poses an extreme challenge, because the state-of-the-art atom traps are only approximately 0.5 K deep for ground-state antihydrogen atoms, much shallower than the energies of particles stored in the plasmas. This thesis will outline the main parts of the ALPHA experiment, with an overview of the important physical processes at work. Antihydrogen production techniques will be described, and an analysis of the spatial annihilation distribution to give indications of the temperature and binding energy distribution of the atoms will be presented. Finally, we describe the techniques needed to demonstrate confinement of antihydrogen atoms, apply them to a data taking run and present the results, making a definitive identification of trapped antihydrogen atoms.