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Using conventional diagnostic methods to test for plant viruses requires knowledge of the pathogens likely to be associated with a host species. This knowledge can either be applied when using a targeted test method (e.g. ELISA or PCR) to identify required tests, or in bioassay, through knowing which viruses will transmit into which assay host. In the last decade High Throughput Sequencing (HTS) has revolutionised plant virology diagnostics, however, the knowledge and skills of the diagnostic virologist are needed to interpret the results of sequencing and to investigate the myriad of novel viruses reported using this technique. This thesis presents a body of published work and an accompanying linking document focussing on the development and application of these diagnostic technologies in a plant health/biosecurity setting. The thesis explores the use of diagnostic technologies in virus detection and discovery, but also in supporting research applications such as gathering the data necessary to support plant health risk assessment or carry out epidemiological studies on vector efficiency. The publications include a review of new virus records from the United Kingdom over a 35-year period, discussing the factors driving virus discovery such as changes in trade, research focus, and diagnostic technologies. Two case studies are presented which investigate diseases of unknown aetiology utilising contrasting approaches to infer the causal agent/s of disease, one utilising biological demonstration, the other experimental design and statistical analysis. Two publications discuss the evaluation and validation of diagnostic techniques. The final publication describes an investigation into the relative efficiency of transmission of potato virus Y and potato virus A by a range of aphid species. The accompanying linking document discusses each publication in the context of the current literature, as well as discussing alternative approaches to inferring causation where traditional biological approaches may not be possible.

Osteoarthritis is the most common form of arthritis and an increasingly significant clinical problem. It is characterised by varying degrees of chronic pain and joint pathology. However, the structural changes to the joint do not always correlate with the severity of pain experienced. Furthermore, a significant number of patients still experience chronic pain even after joint replacement indicating sensitisation in people with OA. The aim of this thesis was to determine the contribution of peripheral and central mechanisms to the initiation versus the maintenance of pain, in an animal model of OA pain. Two models of OA pain were characterised. Both the MIA and MNX model demonstrated significant pain behaviour, joint pathology and increases in activated microglia and reactive astrocytosis in the spinal cord indicative of sensitisation consistent with human OA. Spinal excitability was further assessed in the MIA model and demonstrated significant increases in evoked EMG responses at late but not early timepoints of the model, suggesting a time- dependent sensitisation. Sensory-specific block of TRPVl-positive joint afferents following intra-articular QX-314 concomitant with capsaicin revealed a significant contribution of afferent input to pain at 7 and 14 days but not at 28 days post-MIA. A descending contribution from the RVM to OA pain was investigated in the MIA model at 14 and 28 days. It was shown that intra-RVM administration of a high dose of p-opioid agonist DAMGO significantly attenuated evoked EMG responses. However a low dose of DAMGO attenuated EMG responses only at 28 days post-MIA and not at 14 days post-MIA suggesting an increased sensitivity of the RVM to the effects of DAMGO. Potential alterations in p-opioid receptor G protein-coupled binding were investigated as a potential mechanism driving the enhanced opioid effect observed. Agonist-stimulated GTPyS-binding autoradiography in RVM slices demonstrated a significant increase in GTPyS binding in MIA-treated rats at 28 days but not at 14 days, compared to saline-treated rats. This thesis provides new insights into the mechanisms driving pain behaviour in the MIA model at different timepoints and suggests a switch from a predominantly peripherally mediated pain at an early stage of the model, to a centrally mediated maintenance of chronic pain. These findings may also inform the development of more effective treatment strategies in patients with OA.

For individuals with an acquired brain injury (ABI) who have dependent children their ABI has the potential to impact upon their parenting abilities, skills and relationships. Parenting capacity is an important clinical issue supported by a wide body of existing literature and arises in many specialties, such as adult mental health, learning disabilities and forensics. In the field of ABI the issue of parenting capacity is less developed, yet it remains an important clinical issue. This systematic review examined the current state of knowledge about this within the ABI field and discovered the literature is, as yet, under developed, with little theory and no clear practice guidelines specific to brain-injured parents. Recommendations are made for the development of a parenting capacity assessment protocol for brain-injured parents. Additionally little research has been conducted to explore the effect ABI has on parenting. This empirical study aimed to qualitatively explore the experiences and needs of parents who have suffered an ABI in the last two years from their own perspectives. Interpretive phenomenological analysis was used to analyse the data, leading to the identification of 4 main themes: (1) Multiple Losses, (2) A mix of resigned acceptance and uncertain future (3) Giving and receiving support is part of the healing process, (4) Hopes and aspirations. The results supported the idea of a circular, bi-directional, 'pendulum like' process of movement between experiencing the multiple losses of their parental role and attempting to adapt and adjust to these changes. The clinical and research implications of the systematic review and empirical paper are discussed.

This book examines the questions of how Gypsy ethnicity, identity and history are interlinked in the context of examining various contested narratives or origins and migration. The text is itself a series of narratives and counter-narratives that engage in a self-critical, deconstructive analysis of the underlying assumptions hitherto presented in many, if not most of the previous scholarship regarding the origins and identity of the Gypsies, with particular focus on the contextual and radically contingent nature of all such texts. As such, the primary examination is an historiographical and theoretical consideration of the questions surrounding Gypsy ethnicity and identity. The dissertation also considers to what extent the production of historical knowledge is affected by those who produce it from within and without the Gypsy community or communities themselves. Most especially, this survey examines the production of literatures in Turkish scholarship, as related to the underlying conception of the book arguing for a re-examination of Romanī historiography from east to west, rather than the ‘traditional’ Orientalist and Europe-centric perspectives deployed by much of the previous scholarship. Moreover, the dissertation focuses upon the Turkish lands to argue that the historical experiences of Gypsies in this region are of critical importance in understanding the development of both European Romanī histories and in acknowledging the flawed basis for the universalist conceptions of European Roma identity and political mobilisation, as they are now articulated. The importance of Islam in the origins and history of the Gypsies is stressed. This theoretical framework underlies the interweaving narratives that make up the latter sections of the text, a reconsideration of the sources for early Gypsy history that posits an alternative narrative.

Two studies were designed to examine the relations between early growth and cardiovascular disease in adult life. The first study was a survey of pelvimetry in 1,615 men and women aged 50 yrs or more living in 8 English towns. The mean diameters at the pelvic inlet were smaller in towns with higher SMR's for cardiovascular disease. In both sexes the pelvises of those aged 75 or more had a lower brim index than the pelvises of those who were younger. The second study followed up 449 infants bom in Preston during 1935-1943 who were still living in Lancashire. In both sexes systolic and diastolic pressures were strongly related to placental weight and birth weight. Mean systolic pressure rose by 15 mmHg as placental weight increased from 11b or less to greater than 1.51b, and fell by 11 mmHg as birth weight increased from 5.51b or less to greater than 7.51b. These relations were independent of each other, and of the observed effects of higher body mass index and alcohol consumption. Analysis ofsubjects bom after 38 weeks completed gestation showed that for those with placental weights of 1.25 lb or less, mean systolic pressure rose by 13 mmHg as ponderal index (w/P) at birth fell from greater than 14.75 to 12 or less, while for those with placental weights of greater than 1.25 lb , mean systolic pressure rose by 14 mmHg as head circumference/length increased from less than 0.65 to 0.7 or more. Growth in early life, reflected in the size of the adult bony pelvis, is related to risk of cardiovascular disease. The intrauterine environment, through an effect on intrauterine growth, has an important effect on blood pressure in adult life. Two groups of babies, characterised by birth measurements, have been identified as being at increased risk of raised blood pressure in adult life.

The iron sulphide greigite (Fe3S4) is linked to important diagenetic processes in sediments and to hydrocarbon formation and migration. The magnetic properties of this ferrimagnetic mineral are relatively obscure because it is difficult to synthesise and because it is unstable and therefore thought to be irrelevant to the geological record. However, it is increasingly recognised that greigite can remain stable on geological timescales. It is important to understand the magnetic properties of greigite to identify its presence and timing of formation as it is a proxy for environmental magnetic studies and for hydrocarbon microseepage identification. In this thesis, numerical methods are used to study the magnetic properties of greigite. Using a micromagnetic finite-element method (FEM), important questions regarding the magnetic structure and palaeomagnetic recording fidelity of gregite are addressed. For equidimensional particles, the single-domain (SD) to single-vortex (SV) threshold is found to be d₀ ≈ 54nm and only SV particles >70 nm to carry stable magnetisations over billion-year timescales. A simplified model is developed to study the hysteresis and first-order reversal curve (FORC) properties of non-interacting idealised SD greigite particles. To understand the effects of SV magnetisations on FORC properties, a micromagnetic FEM is used to simulate randomly oriented dispersions of non-interacting greigite in the SV size range. SV effects dominate the FORC signal for particles >70 nm. Implications for FORC diagram interpretation are discussed. Magnetic inter-particle interactions are known to effect the FORC response of magnetic particle ensembles. A micromagnetic FEM is used to study the FORC signal of randomly dispersed strongly interacting clusters of greigite. The FORC response of strongly interacting greigite is found to be similar to that of multi-domain (MD) particles. Since naturally occurring greigite is rarely in a MD state, it is concluded that in greigite-bearing rocks that produce MD-like FORC signals the origin of this signal should be attributed to strong interactions between the particles.