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Meiotic crossovers reshuffle genetic material and are essential for accurate chromosome segregation. Crossovers are a product of meiotic recombination, a complex and highly regulated process, which occurs through the co-ordinated induction and repair of DNA double strand breaks. In the majority of sexually reproducing eukaryotes, the synaptonemal complex (a tripartite ultrastructure compromised of two closely apposed lateral elements adjoined by rod like transverse filaments) is installed between homologs during prophase I; this is essential for normal crossover formation. Using cytological techniques, fluorescent marker assays and novel CRISPR/Cas9 derived mutants the roles of the Arabidopsis thaliana transverse filament protein (ZYP1) were investigated. Additionally, this work also examined a candidate meiotic regulatory protein, the general transcription factor subunit TFIIFb2. This thesis reveals that in the absence of ZYP1, homologs are completely asynaptic yet chromosomes extensively and intimately align during prophase I. Furthermore, zyp1 retains near wild-type fertility and in the vast majority of cases homologs successfully and accurately crossover, though infrequently the obligate crossover is lost. This work shows that in zyp1 mutants HEI10 foci (a cytological marker of class I crossovers), counted at diplotene, are increased by ~2 fold compared to the wild type. Similarly, map lengths measured using fluorescently tagged lines were increased by ~1.5 fold in zyp1 compared to the wild-type. Despite this increase in recombination, zyp1 provides no rescue when crossed to msh5, instead zyp1 msh5 mutants show ~50% fewer chiasmata than msh5 single mutants, indicating that increased crossovers derive from the ZMM dependant class I pathway. In summary, this work reveals that zyp1 is an essential regulator of crossover control. Firstly, zyp1 is required to ensure all chromosomes receive an obligate crossover. Secondly, zyp1 is essential for the normal imposition of crossover interference which limits the occurrence of ZMM derived double crossovers.

Since the election of Hugo Chávez in 1998, Venezuela has undergone considerable constitutional and legislative reforms to establish a more participatory form of democracy. Two of Chavismo’s mechanisms for citizen participation form the units of analysis of the thesis: consejos locales de planificación publica (CLPPs) and consejos comunales (CCs). These sought to bring citizen participation into public policy and planning at the municipal and neighbourhood levels, respectively. The thesis draws from democratic and planning theories, engaging with debates in the literature regarding participation and the issues of bringing democratic innovations into representative democratic systems and planning practices and processes. The thesis responds to a gap in the literature regarding how actors involved in CLPPs and CCs understand these instances of participation. The thesis adopted a constructivist approach involving components drawn from new institutionalism (Lowndes and Roberts 2013) and Bevir and Rhodes’ (2012) strand of interpretivism into an analytical model that Hay (2011) coins ‘interpretive institutionalism’. The thesis elicited the meanings and understandings of citizen participation in local policy making and planning processes held by participants of CLPPs and CCs. Such accounts enabled an analysis of what participatory democracy meant to those active in the processes seeking to establish it. Data collection involved 10 months of fieldwork in two municipalities (Chacao and Libertador) in Caracas including semi-structured interviews with CLPP and CC participants; observation of CLPP and CC participants; and review of corresponding municipal documents, academic literature, and news articles. The findings show that participation was widely advocated by CLPP and CC participants. Ideological/ political beliefs and traditions shaped a) the different ways CLPP members (politician versus community members) conceived participation, and b) CC participants’ understanding of state-civil society relationships. The thesis provides a contribution to democratic theory by providing further insights about the challenges in designing, implementing and embedding mechanisms involving citizen participation, particularly the tensions between representative and participatory forms of democracy. Secondly, by operationalizing Hay’s (2011) interpretive institutionalist model in the Latin American socio-economic context, the thesis showed that marrying constructivist approaches to institutionalism and bringing institutionalist dimensions to interpretivism provide valuable analytical and theoretical insights. Furthermore, the findings enabled an additional link between the interpretive and institutionalist dimensions of Hay’s model to be identified.

SALT HRS (Southern African Large Telescope High Resolution Échelle Spectrograph) is a high-resolution, high-efficiency spectrograph for the 11m SALT telescope in Sutherland, South Africa. The initial optical design work was performed at the University of Canterbury, New Zealand. Revisions to the concept, the mechanical design, manufacture, assembly and testing have been handled by the Centre for Advanced Instrumentation, at Durham University in the United Kingdom. SALT HRS is a fibre-fed echelle grating spectrograph with four operational modes: low-, medium- and high-resolution and high-stability modes, having spectral resolutions of R ≈16000, 37000, 67000 and 67000 respectively over a wavelength range of 370-890nm. The instrument is of a dual channel, ‘white pupil’ design, in which the primary mirror acts to collimate light onto a single R4 echelle grating, and also to focus dispersed light to an intermediate focus. A dichroic beam-splitter separates the dispersed light into two separate spectral channels. Spherical pupil mirrors transfer the separated beams via a fold mirror to two wavelength-specific volume-phase holographic gratings (VPHGs) used as cross-dispersers. Cross-dispersed spectra are then imaged by two fully dioptric camera systems onto optimized CCD detectors. This thesis presents the results of the laboratory testing and specification of several critical sub-systems of SALT HRS, as well as the development of key software tools for the design verification and operation at the telescope. In Chapter 1 we first review the technical development of high-resolution spectroscopy and its specific implementation in SALT HRS. In Chapter 2 we develop a comprehensive throughput model of the entire system based on a combination of as-built performance and specific throughput measurements in the laboratory. This is used to make some specific predictions for the on-sky performance of SALT HRS and the magnitude limits for science targets. We also present a graphical exposure time calculator based on these measurements which can be used by an astronomer to plan their observations with SALT HRS. Chapter 3 contains a detailed treatise on the optical fibre system of SALT HRS. Considerations for the use of optical fibres in astronomy are provided, as are details of an optional double scrambler, and the various instrument fibre modes. Extensive measurements of focal ratio degradation (FRD) are also presented, with testing of input beam speed; wavelength; fibre bending; variable pupil mirror illumination; and vacuum tank pressure dependency. The systems for fibre management are reviewed, as is the fibre bundle assembly process. Testing of two further sub-systems is described in Chapter 4. Firstly the long-term stability of the mirror mounting mechanisms is determined. The advantages of cross-dispersion of echelle spectra using volume-phase holographic gratings are then discussed, and the results of diffraction efficiency measurements are given for both red and blue channel gratings. Modern CCD technologies are examined in Chapter 5, and the blue detector is experimentally characterized using photon transfer and quantum efficiency curves. It is also used for an investigation into cosmic ray events in CCDs. Results from shielding the detector using lead are described, as is an attempt to distinguish the source of the events based on their morphology. Finally, Chapter 6 deals with the handling of data produced by SALT HRS. Methods of wavelength calibration of the spectra are discussed, including the use of Thorium-Argon lamps and an iodine absorption cell. The implementation of a Python based quick-look data reduction pipeline is reviewed, with a description of the processes performed. A summary of the thesis is given in Chapter 7.

Dynamic Nuclear Polarisation (DNP) is a method used to increase the signal available for nuclear magnetic resonance (NMR) experiments. DNP is one of many hyperpolarisation methods and one implementation, so called ex-situ DNP, sees the sample polarised with a stable radical doping agent at low temperature and with microwave irradiation in a magnetic field before transfer to a second higher field NMR magnet to acquire a liquid state NMR spectrum. The primary goal of this project has been to gain an understanding of the underlying reasons for unpredictable ex-situ DNP polarisation failures and to develop methods to overcome these limitations. In the course of the work an additional polarisation mechanism arising from hindered methyl rotors was discovered. This thesis describes the preparation of DNP samples and the way in which DNP-NMR experiments are performed have been optimised. The concept of a co-polarisation agent has been introduced and methods employing a Nuclear Overhauser Effect have been implemented. Additionally the identification and characterisation of a quantum tunnelling effect that is a variant of the commonly known Haupt effect. Finally these methods have been combined in a number of situations to give results that would have otherwise been unobtainable.

Public participation is an increasingly prominent policy in the United Kingdom and elsewhere. This thesis locates one example of participation within wider debates about the constitution of contemporary society, changing welfare-state governance, and the challenges of operationalizing such initiatives. It relates the particularities of this case to practical, policy and theoretical questions. The thesis begins by considering the rise of participation in historical context, relating its aims to social-theoretical commentaries on late-modern society. This framework informs an examination of rationales for participation, an analysis of policy discourses on public involvement in health, and consideration of the challenges of making participation happen. The remainder of the thesis presents the results of an empirical study of one example of participation: service-user involvement in a programme of pilot cancer-genetics services, managed by the third-sector organization Macmillan Cancer Support. Using interview, observational and documentary data collected over a three-year period, it offers a longitudinal perspective on the practice of involvement, drawing on various actors’ perspectives. Considered over five empirical chapters are competing rationales for involvement put forward by different groups of actors, the micro-processes of involvement, and the varied outcomes of negotiations across the seven pilots studied. In reconciling the theoretical and policy literatures with empirical findings, the thesis highlights certain tensions. Policy-level ambiguities permit the coexistence of multiple discourses about the purpose of involvement, the identity of those involved, and the influence it should command, resulting in conflict as participation is put into practice. Policies designed to avoid directiveness and facilitate local discretion create dilemmas for those charged with implementation, especially third-sector organizations whose intermediary role means they must reconcile divergent views of diverse stakeholders in participation practice. The result is a situation where pragmatic negotiations take precedence over any theoretical or normative vision for participation in determining its remit, scope and influence.

The cell cycle is characterised by a series of checkpoints that control passage through the individual phases of the cycle. The most well characterised checkpoint at the present is the mitosis entry checkpoint. Although the cell cycle proteins that control passage through this checkpoint are well defined, the precise mechanism that triggers mitosis entry is unclear at the present time. One hypothesis is that a calcium/calmodulin signal forms part of this mechanism. There is evidence for the role of calcium and calmodulin in this process, however this hypothesis has not gained universal acceptance. This is mainly because it has proved difficult to reliably measure calcium transients associated with mitosis entry. I study the role of calcium and calmodulin in mitosis entry, using the early sea urchin embryo as a model system. My results show that the mitosis entry transient is small and often localised, and this may obscure reliable detection of this transient under certain conditions. I also show that the mitosis entry calcium transient is generated by a mechanism involving inositol 1,4,5-trisphosphate, and is independent of the requirement for protein synthesis during the cell cycle. I use a pseudosubstrate inhibitor of calcium-dependent calmodulin signalling to test whether calmodulin has a function in the mitosis entry mechanism. Blocking the action of calmodulin also blocks mitosis entry. I complement these data by using a fluorescent calmodulin probe to measure calmodulin signals during mitosis. Calmodulin signals can be detected during mitosis entry and also during exit and throughout cleavage. The results also show that calmodulin signals are localised throughout mitosis. When taken as a whole, the data presented in this thesis shows that mitosis entry in the first cell cycle of the sea urchin embryo is triggered by localised calcium/calmodulin signals. The data also suggests that the specificity of action of calmodulin during the cell cycle may be controlled by localisation of the calcium/calmodulin signal to specific areas of the cell.

One hundred consecutive cases of cutaneous anthrax, occurring over an eight month period, are studied. An epizootic in livestock occurring during a period of severe drought was quickly followed by an increase in the human cases, so that no than 42 cases occurred in the fourth month of observation. Of the 100 cases, 31 occurred in children under 10 years old, and 41 in wales aged 10 to 29.The site of the lesion was usually the exposed skin of the head and neck, or upper 1imbs, these sites being more or less equally affected and accounting for over three-quarters of the recorded lesions. The upper 1imbs were more frequently affected in patients who had butchered diseased animals, but it was noted that no lesions occurred on the palmar surface of the hands, or on the soles of tbe feet. Although a history of contact with animals which died was frequently obtained, a history of skin trauma was never obtained. Intramuscular penicillin was effective in all cases, although improvement was not immediate ; there were no fatalities. Respiratory stridor was present in 2 cases, but usually the disease was relatively mild. The mode of transmission of anthrax from livestock to man, and simple but effective measures for its control in a rural community are discussed.

This thesis is about different ways of knowing about people's health, and about what happens when these different knowledges intersect at the frontline of general practice - when people (patients) consult with healthcare professionals. Starting with the accounts of patients, I use institutional ethnography (Smith, 2005b) to explore how patients' (and healthcare professionals') knowledge and practices are socially organised. Within healthcare services, policymakers are coordinating activities to prevent cardiovascular disease, based on knowledge of population health from vast epidemiological datasets such as the Global Burden of Disease project. A suite of 'lifestyle' and pharmaceutical interventions are promoted by policymakers as evidence-based approaches to preventing cardiovascular disease (including heart attacks and strokes) within the population. The flagship Health Check programme aims to prompt people to make changes to their diet and exercise habits, and identify some who will benefit from additional interventions to reduce their risk. However, interviews with patients, observation of preventive care in practice, and the concerns of some general practitioners suggest that cardiovascular disease prevention is not as simple or unproblematic as it first appears; patients' knowledge of their own health needs is often at odds with the preventive care provided. I show how patients look for a discussion with healthcare professionals about how they can best implement preventive approaches, but find that they are given standardised 'automated' responses which do not take account of their own individual circumstances or preferences. Despite prominent notions of 'shared decision-making' and patient involvement written into clinical guidelines, and despite healthcare professionals striving to provide 'patient centred care', tensions persist between an institutional knowledge of prevention and a local, experienced knowledge of what is required to improve health. This thesis explores these tensions, their impact, and how both HCPs' and patients' activities are coordinated remotely from the frontline of general practice.

Background: Surgical quality improvement (QI) research has been conducted with promising results, but translating learning into practice is complicated by incomplete reporting. This research aimed to identify which reporting items are most frequently incomplete, and why incomplete reporting occurs. Methods: A systematic review aimed to identify the current standard of reporting in the surgical QI literature. MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Articles were scored against a modified Template for Intervention Description and Replication (TIDieR) checklist. A qualitative interview study was conducted. QI authors, consumers (those who apply QI research in practice), editors and reporting guideline authors were interviewed to identify why reporting is hard. An author checking exercise involved asking the interview participants to describe how they would replicate an intervention described in a QI article. The article’s authors checked whether their intervention matched the participants’ interpretation. Data was analysed using the constant comparative method. Results: The systematic review identified 100 relevant articles. Reporting of fidelity was absent in 74% of articles; and modifications were absent in 73%. Participants (42) in the qualitative study included: 15 authors, 12 consumers, 11 journal editors and four reporting guideline authors. Of these, 28 were clinicians. Reporting QI is hard because: QI is an emerging field; features of hospitals and journals create tensions for reporting; context is hard to describe; publications are not always intended to be used for exact replication. Discussion and conclusion: QI is a youthful field but stakeholders have well developed aspirations for QI reporting. As the field matures, those involved in QI reporting place value on describing context, identifying active ingredients, and recognising how QI publications are to be used in practice. This research is relevant to an international audience and could help galvanise a renewed sense of importance for reporting.

Through an ethnographic study of intermediary roles-in-context, this thesis makes an original contribution to the understanding of these roles as translational interventions. In English health services research, the second ‘gap’ in translation references a disjuncture between new modes of practice in theory, and the enactment of these in practice. There are different understandings of the problem. ‘One-way’ understandings assume difficulties associated with transferring knowledge into practice. Relational understandings suggest the problem is complex, and that the usual processes by which research is produced are problematic. These posit that co-productive and collaborative forms of research production can assist translation. Either way, the intermediary role is thought to have value as a translational aid. Such roles are known to be context- dependent. Their ‘successful’ enactment is contingent upon understandings of the broader translational problem. The experience of enacting intermediary roles has been little documented and is under-theorised. With recourse to Bourdieusian and other social theory, I found that pre-existing power relationships, modes of practice, perceptions of the translational problem, ontological positions, and ‘fields’ were reproduced and bolstered by macro-level socio-political constraints. These formed boundaries that inhibited the realisation of a new collaborative way of working and impacted on the roles. The actors had little capital that could be mobilised to enhance their roles’ potential as translational interventions. I emphasise the importance of understanding the social fields in which such roles might be deployed in order to endow them with appropriate and sufficient capital to be able to be effective in knowledge translation. I make a case for greater account to be taken of social theory in translational research. I question the degree to which the experimental research paradigm can add to KT understandings, arguing instead that this is a context in which the value of qualitative research should be more widely recognised.

Near‐infrared reflectance spectroscopy (NIR) is investigated as a method of non‐invasive, in situ analysis of contemporary textile material. Besides providing spectral signatures, the advantages of NIR include the non‐contact nature of the reflectance technique and the use of a remote, flexible probe. A spectral database of well‐defined reference material has been collected. This was recorded using a standardised protocol taking into account the need to interrogate objects within a collection. The differentiation of silk and synthetic polyamide can pose particular problems for curators of historic textiles due to the similarities in their visual appearance. NIR spectroscopy coupled with multivariate analysis is investigated for the differentiation of the polyamide sub‐classes, found extensively within textile collections. Two multivariate methods of classification have been applied and it is shown that, with the appropriate spectral processing and calibration, both of these techniques are appropriate for sub‐class discrimination. Synthetic polyamides are frequently found in conjunction with natural organic materials, and are often exposed to the same pest treatments as natural polymers. In the event of an infestation there are a number of eradication measures possible, including the application of raised and lowered temperatures. However, these treatments take unaged aliphatic polyamides above, and well below, their glass transition temperature, respectively. For this reason the stability of new and aged polyamide textile material has been investigated. Polyamide 6,6 test material was tested ‘as received’ and in an artificially aged condition. Samples were subsequently subject to ‐30°C, room temperature or 58°C. In addition, samples were treated with and without the application of a load, enabling an assessment of risk if treated whilst hanging and supporting their own weight. Structural alterations were monitored using polarized and non‐polarized mid infrared spectroscopy, tensile testing and differential scanning calorimetry. In addition, dynamic mechanical thermal analysis creep experiments were carried out to supplement the information provided by the in situ creep tests. It is evident from the results that the thermal treatments have a significant effect on the behaviour and structure of the aged polyamide. The implication for in situ treatment of this material in collections is clear, and must therefore be approached with caution. Analysis of the experimental data suggest that the changes observed can be related to the degree of crystallinity produced by the changes in temperature and by the presence of stress during treatment.