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This thesis addresses the issue of incorporating real world data (RWD) on treatment effectiveness into the health technology assessment (HTA) process. Evidence synthesis methods are evaluated, developed, and illustrated using a case-study assessing the effectiveness of biologic drugs as treatments for rheumatoid arthritis (RA). An extensive simulation study is undertaken comparing existing methods, under a Bayesian framework, for performing a pairwise meta-analysis combining randomised controlled trials (RCTs) and single-arm trials (SATs) using aggregate triallevel data (AD). The simulation study results suggest that prior-based methods provide a  exible and robust approach to incorporate SAT data into a meta-analysis, by defining an informative prior distribution for the pooled treatment effect which can be down-weighted according to pre-specification or commensurability with the RCT data. Novel methods are developed for performing a network meta-analysis combining RCTs and SATs using a mixture of individual participant data and AD, with covariate adjustment on the baseline response. The application of the developed methods to data from a network of RCTs, assessing a number of biologic drugs versus placebo as treatments for RA, suggests that the predicted baseline response for SATs can significantly in uence the pooled treatment effect estimates. The impact of methods for incorporating RWD (including disease-registry data) is demonstrated by repeating the cost-effectiveness analysis from a previous HTA report, using the updated clinical effectiveness estimates. The incremental cost-effectiveness ratio estimates, comparing biologic versus non-biologic treatment strategies for RA, were higher when RWD were included and treatment effect estimates based on registry data were lower compared to those based on RCTs alone. RWD can provide information regarding the potential variability in cost-effectiveness results, and should be incorporated into the evidence synthesis to improve HTA decision-making.

There are debates in the literature regarding the cognitive processes involved in search, within small-scale environments, as per visual search, and in large-scale environments, more akin to foraging. My thesis aims to shed light on some of the similarities and differences between search tasks implemented in small-scale 2D displays and 3D virtual reality settings, simulating larger environments. In reference to these notions, my research investigated three core questions: are visual search and foraging the same or different constructs, are templates held in working memory singularly or simultaneously, and what determines our search behaviour. The current research found that when implementing similar tasks in visual search (via 2D small-scale environment) and foraging (via 3D large-scale environment), significant differences were observed in terms of cognitive requirements, task difficulty, and influences on search strategies. Active mental templates during search can be maintained and utilised simultaneously - with greater incentives do so depending on task demands. My study also revealed that for factors which affect search decisions, stimulus distance is a more influential factor for search strategies compared to the "speed" of the searcher. As for the impact of individual differences (via bilingualism), bilingual individuals exhibited a greater proficiency in implementing advantageous (efficiency-boosting) search strategies, without sacrificing the accuracy of their selections - attributed to enhanced inhibitory control (in comparison to monolingual individuals).

This thesis investigates Muslim women's lived experiences of Islamophobia in Greece. The first research of its kind, it documents their experiences and understandings of their victimisation, and the coping strategies they develop and deploy. Beginning with a historical overview of Muslims in Greece from the 13th century onwards, the opening chapter identifies and elucidates the Greco-specific relevance of history, culture, Orthodoxy and geography on contemporary Islamophobia. From here, this thesis examines the nature and scope of Islamophobic victimisation and the associated discourses and practices that function to 'Other' Muslims. It also focuses on what is currently known about gendered Islamophobia. The next chapter explores the methodological approaches underpinning this research, justifying the qualitative methods preferred as well as the process of engaging participants and the methods for collecting and analysing the data gathered. Positionality and reflexivity are also considered. Three findings chapters follow, which draw from interviews with twenty-four Muslim women in Athens and Western Thrace. In the first, the nature of Islamophobia and the victimisation of Muslim women is evidenced and considered, paying close attention to factors increasing their vulnerability and the challenges faced by them in integration, acceptance, employment, and combating stereotypes and discrimination. In the second, the women's response to actual and prospective victimisation as also its impact is examined. Here, three new categories of coping strategies are evidenced: engaging in conversation, reciprocating abuse and downplaying significance. The final findings chapter centres on the factors that determine the prevalence and severity of Islamophobia in Greece. The reasons for not reporting Islamophobia are also considered. In conclusion, the themes and concepts developed throughout are reflected upon. This study makes a timely and significant contribution to what is currently an embryonic body of work and puts forward much needed new knowledge that has social, political and cultural salience.

As first line of defence, microglia play a critical role in maintaining the central nervous system (CNS) homeostasis. However, constantly activated cells can generate a continuous inflammation that results in neuronal dysfunction and cellular death. Furthermore, microglia express specific enzymes of the kynurenine pathway (KP) which have a strong influence on the pathological dynamics of the CNS. In particular, the activity of kynurenine-3-monooxygenase (KMO) during the immune response causes the production of neurotoxic metabolites. Giving that KMO is predominantly expressed in microglia and that alteration of the immune response in these cells have been established to be partially responsible in the pathology of several neurological diseases, the aim of this study was to better understand microglia physiology by employing pro-and anti-inflammatory molecules and assess possible downstream effects, together with a focus on KP manipulation through KMO in order to investigate whether the inhibition of the enzymatic activity affects microglia immune response and gain insights into the contribution of these players during health and pathological scenarios. In this project it was showed that immune stimulation has a significant impact on the up-regulation of KMO expression as well as specific features of microglia activation, such as production of pro- and anti-inflammatory biomarkers and release of extracellular vesicles. Notably, all these effects were dampened by the addition of dexamethasone (DEXA), highlighting the use of glucocorticoids for diseases associated with neuroinflammation. KMO inhibition did not produce the same hypothesised results, however, a possible novel relationship with the circadian clock has emerged. Transcriptomic analysis supported and extended the data obtained by highlighting enriched pathways activated by tumor necrosis factor (TNF)-α and those down-regulated in samples co-treated with DEXA. Finally, the findings described here accentuate the importance of species-specific mechanisms that become crucial when results obtained by experiments in animals are translated to human diseases.

Objective: Diseases of the thoracic aorta (TADs) are increasing in prevalence. Non-syndromic thoracic aortic diseases (NS-TADs) lack external physical features and can present as an acute aortic syndrome. Tailored genetic and imaging screening of first- (FDRs) and second-degree relatives (SDRs) of patients affected by NS-TADs may enable early diagnosis and allow appropriate surveillance or prophylaxis. Methods: We performed a Delphi exercise to inform a research proposal that could evaluate a screening programme for TADs. Next, we conducted a feasibility study on 16 NS-TADs patients, along with their FDR and SDR. Each participant underwent imaging and genetic evaluation, together with a physical examination and a psychological assessment. Results: In the Delphi exercise, a panel of 34 experts and a pool of 87 patients discussed themes such as preferred imaging technique, age criteria for screening, and optimal trial design. Suggestions included routine storage of DNA and screening test consent at first appointment. For the feasibility study, 70 participants, with median age of 48 years (range 18-85), were recruited. Imaging diagnosis was obtained in 24.1% of relatives, and a genetic variant was identified in 3 families. Overall, imaging or genetic surveillance, or new secondary prevention, was indicated in 68% of the participants in the familial group and 54% in the sporadic group. Conclusion: Our results showed an important diagnosis rate with imaging for relatives of NS-TAD patients, and a potential role for genetic testing. With the results of our Delphi exercise, and the evidence gap identified by the review, our data supports the development of a research programme on cascade screening in people at risk of TAD.

Mitigating methane (CH4) emissions is of uttermost importance to meet the targets of the Paris Agreement as the second-most important greenhouse gas in terms of radiative forcing. The atmospheric CH4 burden is rising, and has been doing so since the industrial times predominantly due to human activities. Novel airborne and space-based instruments have the potential to address the challenges towards detecting and quantifying localised emissions. The ultimate goal of this thesis is to use these state-of-art remote sensing measurements to improve inventories currently informed by modelled and process-based data. CH4 point source emissions require a high spatial resolution to distinguish between different sources and a high spectral resolution to characterise the CH4 component of the atmosphere. This thesis uses the hyperspectral imager AisaFENIX, with a spectral range capable of measuring CH4 in the SWIR around 2300 nm and a spatial resolution of about 2.5 m2, in the first tailored flight campaign with the BAS Twin Otter aircraft over UK CH4 point sources. Based on a fast data-driven retrieval algorithm to infer atmospheric concentrations of CH4 from spectroscopic measurements, it successfully explores the detection limits using real and simulated CH4 plumes. The detection limit suggests that assuming a constant rate of emissions throughout the year, even the highest reported UK emitter for 2018 (Drax Power Station) would not be detected. The retrieval has applications beyond the flight campaign and can be easily adapted for the next generation of hyperspectral satellites. This thesis also investigates the use of the Sentinel-5P satellite, with unprecedented daily global coverage and spatial resolution of around 7 km2, to quantify CH4 emissions over areas with limited observations. By identifying persistent CH4 enhancements, this thesis has successfully quantified emissions in South African coal mines and oil and gas facilities in Egypt. The estimates in this thesis for South Africa are in good agreement with the EDGAR v4.3.2 inventory, which underestimates emissions in Egypt by a third probably due to uncaptured fugitive emissions.

In December 2025, the joint ESA and JAXA BepiColombo spacecraft will enter orbit around Mercury to begin a two-year mission. Among the 16 instruments aboard BepiColombo is the Mercury Imaging X-ray Spectrometer (MIXS), which offers high-resolution (~10 km per pixel) imaging capabilities for low-energy (0-10 keV) X-ray photons. This information will be used to determine the elemental composition of Mercury's surface. The novel imaging capability, requires a new data analysis method to help maximise the instrument's science return. In order to prepare for this, a ground-reference facility (GREF) has been built and the first tests of its performance are reported here, demonstrating that this facility is ready to enable further characterisation and calibration of the instrument and data analysis methods in the coming years. This thesis presents the initial work done to develop and test a new "fundamental parameters" model for X-ray fluorescence. Testing the model against laboratory data from the GREF revealed the next steps in the development of both the model and the ground testing needed to demonstrate that it will meet the scientific goals of MIXS. MIXS requires solar flares for high-resolution imaging, therefore targets of particular scientific interest need to be prioritised, to avoid valuable data being deleted onboard the spacecraft, due to mission-level telemetry constraints. Prioritisation began with cataloguing Mercurian complex craters, revealing a correlation between peak-ring basins and the high-magnesium terrane (HMT), implying the basins may be responsible for the elevated magnesium/silicon ratio. Investigating the correlation determined a list of fifteen targets that MIXS should prioritise, in order to demonstrate whether the correlation is indicative of causality or not. MIXS will determine the composition of basin features, improving our understanding of the origin of the HMT, a feature on Mercury's surface that is the source of much debate in the community.

The tumour suppressor p53 is considered to be one of the most studied proteins of all time, and yet much remains to be discovered about this enigmatic protein. As a stress response protein, p53 is able to coordinate multiple signalling inputs to alter cell fate to either cause cell cycle arrest in the form of senescence or death via apoptosis. With regards to senescence, there is a paucity of data demonstrating how p53 elicits and maintains this phenotype. To overcome this gap, interactors of p53 in the context of senescence were identified using two main approaches, immunoprecipitation and proximity labelling of p53, in a well characterized cellular model of senescence. An IP at different times over the first 72 hours of senescence induction analysed by tandem mass spectrometry identified known interactors of p53, such as heat shock proteins and 14-3-3, but also potential novel interactors such as Synemin. Proximity labelling studies were next conducted by generating chimeric p53-APEX2 proteins at both the N and C terminal ends of p53 to identify further possible interactors. Following labelling with biotin, samples over 72 hours were similarly analysed by tandem mass spectrometry. This resulted in the identification of numerous proteins, local to p53 throughout the early stages of senescence and potentially implicated in various aspects of the senescent phenotype, such as the SASP, lysosome translocation, cytoskeletal organisation, and cell cycle arrest. Together, these proteins could be setting up a "pro-senescent" balance that would help determine p53-dependent cell fate decisions. This is the first dynamic interactome of p53 in the first stages of senescence, and it provides novel insights on how p53 mediates this phenotype. Among the known modulators of p53, we further studied the retinoic acid receptor, Stra6, which increased ROS and p53 levels and reduced cell viability when expressed in DNA damaged cells. Stra6 may play a role in cell fate decisions by enhancing apoptotic responses. This connection between p53 and the retinoic acid pathway warrants further attention to fully understand the mechanism at work.

This thesis presents the outcomes of two qualitative case studies which investigate the value and effectiveness of a coursebook according to the perceptions of two Libyan English language teachers and their learners. Specifically, it focuses on the speaking activities, and the extent to which the study participants perceive these to be effective in the development of oral fluency. It illuminates key aspects of the coursebook activities which aim to develop learners' oral fluency with a focus on how they are actually taught. A two-level approach (macro and micro) to data collection, including coursebook analysis using Littlejohn's framework, individual interviews with the teachers, focus group interviews with learners and semi-structured classroom observation were used. In answering the research questions, the following themes are addressed: the coursebook's design; classroom teaching to examine how the coursebook is used by both the teachers and their learners; and the teachers' and learners' perceptions of the coursebook's speaking activities as they relate to the promotion of oral fluency. The findings of the analysis reveal that some coursebook activities can play a role in encouraging oral fluency. However, the classroom observation revealed that the teachers tend to focus more on developing learners' general oral proficiency, rather than oral fluency. While the teacher interviews demonstrate a high level of confidence regarding the teaching of oral fluency, the analysis indicated that the teachers' knowledge of oral fluency, and by extension, the kinds of classroom activities that can promote oral fluency, were limited. The research study contributes to the literature on developing oral fluency by examining under-researched aspects of coursebook design, which in turn offered a focus on the coursebook activities in use (through the observation of the teachers and learners) and their perspectives on it (through the interviews). There are only a few studies that evaluate coursebook materials by their end-users.

The steady flow around a rotating sphere at large Reynolds numbers, up to 105, is obtained and analysed which has also been adapted with a temperature dependent viscosity. The Navier-Stokes problem is reduced to solving simpler PDE systems in distinct regions around the sphere where it is determined that the boundary layer approximation is once again an excellent model of the flow close to the sphere and far above the equator. Stewartson's (1958) model of the equatorial flow is solved for the first time using a multi-grid method but it is found that this gives arise to unobserved behaviour compared to Calabretto et al (2019). A new model, based on Stewartson (1958), but amended with added azimuthal terms qualitatively describes the flow well compared to Calabretto et al (2019) and suggests that the flow in this area is more complicated than once thought. The radial jet is subsequently determined and displays the hallmark characteristics of jet flow however as the Reynolds number increases, the length of the jet slightly decreases. This is unexpected as one would expect the distance traversed by the jet to increase with Reynolds number, however this is suspected to be due to the position of the inlet but further tests are required for confirmation. The full flow has been compiled and is ready to be used in stability calculations or for any other use required for Reynolds numbers less than 105. Additionally, a temperature dependent viscosity has been successfully added to the steady flow where similar behaviour, with respect to the sensitivity parameter λ, is observed to that of the heated rotating disk flow examined by Miller et al (2020) and the heated sphere boundary layer by Molla & Hossain (2006); namely, that reducing outflow is favourable to the transfer of heat.

This thesis has two main objectives: first, to reveal the impacts of museums' creative learning programmes on children's wellbeing and explore the underpinning reasons for these impacts; and second, to offer recommendations for how creative learning could be used within Chinese museums to support children's wellbeing. To achieve the first objective, this research involved two key groups of research participants: children aged 6 to 12 (namely children of primary school age in China, n=193) and museum practitioners (n=15) in China. To evaluate the impact of museums' creative learning programmes on children's wellbeing, pre- and post-session quantitative methods and end-session focus group discussions were employed. Moreover, this research was inspired by 'children's museology', a growing research area that involves children in the production of museum content and programming. Thus, children were provided with appropriate ethical considerations, and their museum experiences were accessed in such a way as to prioritise their own perspectives. Interviews with museum practitioners in China authentically revealed their motivations, preconceptions and understandings of museum learning, children and wellbeing, which shaped their museum programming with children. A four-domain wellbeing framework was developed, encompassing social, emotional, physical, and personal development, to enhance children's museum experience and care for their wellbeing. This interdisciplinary research seeks to strengthen museums' awareness of their role in promoting wellbeing, encouraging museum practitioners to develop museums as assets for promoting wellbeing for wider populations, and helping children express their wellbeing rights and capabilities.

This research had been focusing to develop a large format UV photon counting detector which matches the requirements of next-generation space telescopes, such as the proposed Large UV Optical Infrared Surveyor. The LinoSPAD, SAMPIC, and TOFPET electronic fast timing readout device performances were investigated. They were operated in multi-channel mode of measurement. The APD detector was used to detect the illuminating light source for LinoSPAD and TOFPET. SAMPIC and TOFPET were tested with an MCP detector using a pixelated readout device. The three very fast timing electronic multichannel readout devices with two detectors, were tested and analysed in the experimental work. The accuracy of their energy and timing characteristics such as energy in ADC units, signal amplitude, time resolution and time-over-threshold, was measured to see if they provide accurate charge measurement necessary for high spatial resolution with the MCP detector. The various centroiding techniques were used to calculate the centre position of the charge cloud footprint. The measurement of energy, amplitude, and time-over-threshold performance of the SAMPIC and TOFPET was evaluated for sub-pixel centroiding to achieve high spatial resolution with the MCP. The signal's amplitude and time over threshold centroiding were successfully used to calculate the centre position of charge cloud footprint. All-pixels Gaussian fitting can be used to centroiding the charge cloud footprint with highly precision, but lower accuracy as the calculated positions have an offset from the actual position. The 3-cross Gaussian, Parabola, and Lorentzian fitting appear more suitable to centroiding a charge cloud footprint with some acceptable linear distortion.

Conodonts are a group of extinct jawless early vertebrates. They have one of the most abundant and temporally well resolved fossil records, spanning over 300 million years. While their evolutionary significance is well recognised, little is known about their ecology. This is largely due to the absence of extant animals with homologous feeding tools to compare them with. In this thesis, we review previous research into the feeding function and dietary ecology of conodont elements, critically evaluating the analytical power of the methods used. We demonstrate that a new suite of methods, dental topographic metrics, can successfully infer diet between distantly related clades with nonhomologous feeding tools. Application of dental topographic metrics and consideration of biophysical scaling constraints demonstrates that conodont consumer niche breadth was comparable to modern mammals. Conodont dietary niche was found to be closely associated with descriptive morphofunctional categories, grouping them into dietary guilds. Variation in the relative abundance of dietary guilds throughout their fossil record shows a succession of three distinct faunas, a rapid origination of different ecologies in the Great Ordovician Biodiversification Event, an ecological Devonian Nekton Revolution and little change in ecosystem structure at mass extinction events. High temporal- and ecological resolution analysis of the Hangenberg Crisis extinction event demonstrates that little overall change in ecology across the event was brought about through the selective extinction of hard diets and rapid origination of similar ecologies in the immediate recovery period. This thesis represents a marked change in our understanding of conodont diets. Through the development and application of dental topographic metrics we have unlocked the conodont fossil record for palaeoecological study with an emphasis on diet. We anticipate this to be a starting point for more sophisticated analyses of marine ecosystem structure through time, not only using conodonts but also through the analysis of other enigmatic fossil records.

The ground-breaking digitisation of the British Library's vast newspaper archive over the past ten years has been a crucial component in driving this thesis's examination of how two English provincial daily newspapers reported and editorialised the Anglo-Irish War (1919-21) and the ensuing long-running London Peace Conference (1922). This forensic research fills a gap in the historiography of this crisis by revealing the intense interest shown in the emergency by English provincial dailies, an area which has received little scholarly attention. This new examination therefore makes a significant contribution to the establishment of a more complex and complete picture of what the English public were being told about the War through the narrative in the privately owned Liberal Derby Daily Telegraph and Sheffield Independent. This argument has been reached through examining individually every copy of each newspaper from 1 January 1919 to 15 July 1922 for reports from the emergency. Also evaluated are editorial comments on developments, as well as observations, on the progress of the subsequent peace negotiations in London which received a noteworthy amount of detailed reportage. The chapters in the proposal make-up a kaleidoscope of how significant facets of the crisis were relayed to the English, such as reportage predominantly criticising the Crown forces as opposed to the rebels, particularly in relation to reprisals. All coupled with the impression of an evolving picture of a gradual descent into both chaos and lawlessness as well as an assessment of the Coalition government's self-inflicted loss of control of the crucial and influential news agenda from Ireland. Reportage of the most notorious incidents are also investigated. This builds a picture of the significance of news from Ireland to these English daily provincials which would have been the primary sources of up-to-date coverage of the War. This proposition argues for the importance of the provincial daily press in an era when news coverage was limited largely to print media. Coincidentally, this thesis also highlights a significant, undervalued contribution to academic debates over the Anglo-Irish War by underlining an influence which has been ignored by academics, possibly due to the difficulties in accessing provincial newspaper prior to the mass digitisation of newspaper archives by the British Library which has now created new opportunities in the field of digital humanities.

Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia in clinical practice and can increase stroke risk five times. AF also impairs quality of life (QoL) dramatically. Pulmonary vein isolation (PVI) has recently emerged as a successful intervention to treat symptomatic paroxysmal atrial fibrillation (PAF), superior to antiarrhythmic drugs (AADs). PVI could be performed using point-bypoint radiofrequency ablation (RF) or one-shot cryoballoon ablation (cryo). This thesis included a single-centre retrospective analysis comparing clinical outcomes in RF and cryo at 12 months. Pulmonary vein (PV) reconnection patterns after failed ablation were also examined to improve both ablation techniques in particular anatomical sites. The outcome was also calculated from a patient perspective using QoL paper questionnaires. The P wave represents atrial depolarisation and alterations in its morphology could demonstrate changes in atrial electrophysiology. P wave parameters using digital 12 leads electrocardiogram (ECG) directly before and after ablation were utilised to compare differences between both ablation modalities and to predict outcomes. P wave parameters were also used to predict repeat ablation outcomes in patients who failed their first PVI. The utility of P wave mapped by body surface mapping (BSM) was explored in predicting 12 months success rates for external direct current cardioversion (DCCV) in persistent atrial fibrillation (persAF). RF and cryo demonstrated similar clinical outcomes at 12 months, similar P wave parameter changes, similar QoL improvement regardless of additional ablations, and similar PV reconnection patterns. However, there was a trend toward right lower pulmonary vein (RLPV) reconnection after failed cryo. Multiple P wave parameter changes were observed after first and second ablations. However, the change in P wave terminal force in V1 (PTFV1) after second ablation was the only potential predictor of successful outcomes at 12 months. Increased PWDc was also predictive of DCCV failure at 12 months in patients on amiodarone. This thesis provided insights into the utility of P waves in comparing ablation techniques and predicting PVI and DCCV outcomes.

The purpose of this thesis was to assess the impact of healthy older age and older age with Alzheimer's disease (AD) on the structural and functional integrity of the visual system and on key associated measures of visual performance. A systematic review of the literature (Chapter 2) revealed a significant impact of AD on the retina, where significant thinning in the ganglion cell layer of the retina, most commonly in superior and inferior retinal nerve fibre layer (RNFL) quadrants is consistently reported. Evidence of amyloid-β plaques in the lateral geniculate nuclei of the thalamus and in primary visual cortices (area V1) was also identified, accompanied by some evidence of gliosis in the magnocellular visual pathways and by neuron and glial cell loss in the parvocellular visual pathway. Reduced neural activation in areas V1 and V5/MT was also noted. In the context of visual performance, age and AD-related deficits have been reported in several visual domains including sensitivity to contrast, colour, depth, and motion. Self-report studies confirmed that dementia is associated with visual impairment and reduced vision-related quality of life beyond that experienced as part of the 'typical' aging process and that people with dementia are aware of the visual changes they experience (Chapter 3). The experiences of visual impairment by people with dementia were confirmed by their carers (Chapter 4). A series of clinical and psychophysical assessments of visual performance confirmed deleterious effects of AD on the visual system beyond that observed in healthy older age. This included AD-related deficits on fundamental aspects of visual perception, reflected by deficits on tests of colour discrimination and motion perception (Chapter 5). These effects extended to visual cognition, in particular to stimulus identification and visual search performance (Chapter 6).

Background: Physiological and blood biomarker changes could give new insights into brain injury mechanisms associated with paediatric congenital heart disease (CHD) surgery. Objectives: This thesis aimed to characterise physiological and blood biomarker changes associated with paediatric CHD interventions. Methods: A systematic review was performed to investigate the incidence of perioperative brain MRI findings from studies that had conducted both pre- and post-surgery brain MRI. As preparation for our clinical study, a neonatal TCD probe holder was developed, and the accuracy of our TCD equipment was verified through development of a Doppler phantom mimicking the middle cerebral artery. Finally, a prospective observational study was conducted involving measurement of pre-, intra- and post-operative cerebral blood flow velocity (CBFV), physiological monitoring, analysis of blood-based brain injury and inflammatory biomarkers, and brain MRI in infants undergoing CHD interventions (on-pump, off-pump, and catheterisation). Results: Our systematic review demonstrated that new brain MRI findings are typically present in 51% of infants following CHD surgery. Our in vitro study provided a better understand of TCD CBFV measurements and revealed differences between manufacturers at high velocities. CBFV monitoring using TCD at various perioperative time-points in 38 CHD infants revealed differences in cerebral haemodynamics between CHD repair groups. Analysis of 12 blood-based brain injury and inflammatory biomarkers in 20 infants revealed high levels of biomarkers, especially in infants undergoing on-pump surgery. Finally, a case-study is reported, which includes brain MRI findings in a 3-month-old infant who underwent trans-catheter CHD repair. Conclusion: TCD monitoring, blood biomarkers, and MRI, could be valuable in addressing knowledge gaps around perioperative brain injury and have the potential to support the evaluation of methods for improving outcome. Further work should also assess neurodevelopmental outcome for comparison with TCD, blood biomarkers, and brain MRI outcomes around the time of surgery in a larger group of patients.

In 1964, the Anglo-German Agreement was formalised, which saw the Federal Republic of Germany provide the United Kingdom with a £1 million political settlement to form a compensation scheme for British victims of Nazi persecution. This bilateral agreement was part of West Germany's wider international policy between 1959 to 1964, to settle claims for compensation with several Western European nations for the crimes of its fascist predecessor. By exploring the legal aftermath of the Nazi atrocities from a British perspective, this research contributes to a transnational history on how European nations dealt with the dark and difficult Nazi past, both on a state and ground level. This thesis investigates the development of British legal approaches to seeking justice for the mass murder and war of extermination perpetrated by the Nazi regime, with a strong focus on some of the victim responses to this. This doctoral research firstly examines the ways, and extent to which, the British Government negotiated and administered redress for Nazi victims between 1945 to 1969. This is complemented by my analysis on the different ways in which some of the victims of Nazi persecution being addressed within these British policies reacted and responded to them. Specific attention is given to the many poignant and emotional petition letters which were sent to the British Government by Nazi victims who had been unsuccessful in their applications for compensation under the Anglo-German Agreement. The appeals from both individual victims and collective groups who united to campaign against the British Government are explored. These petition letters showcase that many victims did not simply accept having their compensation claims rejected, and they used any medium available to them to have their voices heard. Voices which demanded justice for a time in their lives when they had been so grievously denied of this. This thesis gives space to, and represents, the voices of these Nazi victims.

This thesis contains four essays on the economics of organized crime and the empirical analysis of social networks. The first chapter provides a review of the recent economic literature on the impacts of organized crime on elections, and on public policies. Politicians indeed represent a major target for criminal organisations as they shape political decisions and policy implementation. The review discusses two central challenges characterising the literature, namely the measurement of organized crime and its potential endogeneity. The second chapter argues that higher electoral competition may reinforce the position of politically active criminal organizations, which can endorse politicians in exchange for favors. The paper formalizes this intuition and test it on Italian electoral data, using the 1991 electoral reform as an exogenous source of variation in electoral competition in one of the two branches of the Parliament. A series of triple-difference and differencein-differences estimates suggest that, after the reform, mafia-prone areas reported higher vote shares awarded to the party traditionally supported by criminal organizations and a larger dispersion of votes across candidates of the same party. The third chapter applies Network Analysis (NA) to study the interactions between criminal organisations and the wider society by analysing the connections between mafia members and the political, economic and social elites (e.g., politicians, public officials, policemen, entrepreneurs) in Sicily, the homeland of the Sicilian mafia. The analysis is based on a novel network dataset built by encoding information coming from the archive of the Italian Anti-mafia Commission, describing relationships of collusion and exchange of favours. So far, the application of NA has been limited to the relationships within criminal networks. This paper moves a step further as it also considers the interactions between mafia members and individuals belonging to the social, political and economic elites. The study analyses the "topological" role of mafia bosses, and shows that mafia bosses strategically position themselves in the social network as an interface between the criminal and the legitimate world. Finally, the fourth chapter studies peer effects in the consumption of cultural activities by exploiting a unique individual-level longitudinal dataset on daily museum visits made by cardholders in the metropolitan area of Turin, in Northern Italy, between 2012 and 2019. The underlying peers' structure is represented by a network in which cardholders are connected on the basis of information about the exact time and location of their visits.

Current literature has consistently indicated the detriments of high levels of foreign language anxiety on language performance. However, a crucial piece of the puzzle remains missing: how learners may systematically learn to manage their own foreign language anxiety (FLA). The current study was designed with the argument that there lacked theory-driven literature to drive organised research. By drawing on an empirically-validated theoretical model in psychology called the Process Model of Emotion Regulation (Gross, 1998, 2005), the present mixed-methods study investigated the use of two emotion regulation strategies, cognitive reappraisal and expressive suppression, among a sample of Chinese learners of English as a foreign language (EFL) at a university in Hong Kong. It also examined the relation between emotion regulation and FLA levels, and as a secondary line of inquiry, how emotion regulation influenced the link between FLA and second language motivation. The quantitative questionnaire surveyed 495 learners from different undergraduate years and academic disciplines. Sixteen informants of three levels (high, medium, low) of FLA were then selected for the qualitative research, of which the main component was a stimulated recall interview. Because of the COVID-19 pandemic, data collection was conducted online. Results showed that the two emotion regulation strategies were not often used, with cognitive reappraisal being more frequently used than expressive suppression. Cognitive reappraisal was less common and popular among learners with low English proficiency. The likely reason is twofold: a) cognitive reappraisal is complicated and demands cognitive resources; b) the low English proficiency strains cognitive resources. Expressive suppression had a more pervasive positive relation with FLA. Cognitive reappraisal was negatively correlated with FLA but the influence was limited to speaking with native speakers. Three important over-arching conditions were identified to be necessary for effective FLA regulation. Methodological limitations and suggestions on pedagogy and future research are discussed.

Paraconodonts represent the earliest candidate vertebrate feeding structures in the fossil record. However, critical questions regarding individual element growth and function, and apparatus structure remain unconstrained. To address these questions, large assemblages of elements from the Deadwood Formation, Canada and Alum Shale Formation, Sweden were examined. The new assemblage of SCFs from the Deadwood Formation has yielded over 1800 paraconodont elements, including 536 Westergaardodina spanning six species, two of which are new. Biological taxonomy based upon ontogenetic development of elements has been presented in Westergaardodina for the first time. Taphonomic examination reveals that elements were flattened and partially demineralised during preservation. Histological examination of phosphatic coniform paraconodont elements using tomographic imaging has revealed four distinct internal grades of basal accretion that are highly variable among genera, supporting a polyphyletic Euconodonta. Observations under transmitted light, scanning electron, and tomographic microscopy reveal that Westergaardodina elements grew through at least two distinct modes of morphogenesis. The first is modified basal accretion with distinct lateral allometry, and the second involves the incorporation of distinct units into a united element superstructure. This mode of development is observed in derived euconodont elements and other basal vertebrates but is the earliest known example of this in vertebrate feeding structures. Finally, quantitative functional analyses of damage patterns and sharpness of Westergaardodina preclude it from an external body function and indicate it was used directly in food processing as a slicing surface. The apparatus structure of Westergaardodina remains unknown but is clearly separate from those currently known in conodonts, further adding to the known diversity of the earliest vertebrates. The combined results of this work have highlighted the hitherto underappreciated diversity present within the skeletons of the earliest conodonts and vertebrates extending to both their growth, and function. Paraconodonts were clearly a key component of late Cambrian ecosystems.

This PhD thesis explores a disconnect within contemporary heritage management that, through the international Conventions, calls for inclusivity, Indigenous knowledge recognition, and the participation of Indigenous peoples in heritage yet continues to marginalize these knowledges and practitioners. It is anchored in geography where I have found synergy with a subdiscipline known as Indigenous geographies that is calling for increased participation and new methodologies that instead marginalize still-dominant colonial practices. Drawing on a variety of Indigenous and ally scholars I demonstrate the ways that Indigenous knowledges are not accommodated within current heritage management structures. I also posit a need to explore cultural institutions such as inclusive museums for models of better practice and collaborative engagement. My own professional career has not only demonstrated the benefits of such ways of working but also dictated how I was willing to engage in a fieldwork project and facilitated a suitable project. This fieldwork, undertaken through a technical assistance at the request of the Pueblo of Cacha, high in the Andes of Ecuador, foregrounded the work requested by the Pueblo yet demonstrated the benefits and pitfalls of bridging knowledge systems, with strongly positive results in the community yet an incomplete attempt to dislodge the dominant heritage practice paradigm. My ethnographic account of the time in Ecuador uses photography and a series of vignettes to explore the partial knowledges shared, then assessments through both professional and academic lenses. Indeed, this dichotomy of practitioner and academic is evident throughout this thesis, mirroring the challenges of working in new and different ways.

Mitochondria are the major source of energy production in the eukaryotic cell, and mitochondrial transcription is often dysregulated in cancers, ageing, and neurodegenerative diseases. Dissection of mitochondrial transcription at singlemolecule resolution - from initiation to escape to elongation - can provide new insights into mitochondrial transcriptional control and provide new methods to the field of real-time single-molecule spectroscopy. I have developed the first singlemolecule system to dissect transcription by the human mitochondrial RNA polymerase (RNAP), directly visualizing interactions between human mtRNAP and transcription factors TFAM, TFB2M, and TEFM, engaged in initiation and elongation from the Light Stand Promoter (LSP). My work revealed that mtRNAP preinitiation complexes assemble sequentially from monomeric components. TFAM binds to LSP first and recruits mtRNAP, which then recruits FB2M. Upon mtRNAP escape, TFB2M dissociates and immediately gets replaced by TEFM. I have measured all the characteristic binding and dissociation rates for all of the proteins involved, and have identified two key limiting steps in mtRNAP initiation: (i) mtRNAP recruitment to LSP is a slow process (kon ~= 1.1x105 M-1 s-1), consistent with TFAM finding and bending promoter DNA before recruiting mtRNAP; (ii) TFB2M makes several attempts to bind to mtRNAP and to, presumably, melt the promoter - at an overall initiation rate coefficient ~= 2.3x106 M-1 s-1. My measurements provide benchmarks for future analyses of mtRNAP transcription in live cells. In addition, methods and sensors developed will benefit researchers focused on long-term single-molecule imaging of functional molecular interactions in real-time.

This thesis examines how the agential capacities of disadvantaged market actors are developed interactively in the Philippine coffee actor-network. Substantial Market Studies research explores the role and expertise of marketing practitioners, academia, government and other actors in the organization of (good) markets. Yet, research on the agency of disadvantaged market actors and their role in constructing or shaping (good) markets remains underexplored. Using ethnographic methods, this thesis explores the network of socioeconomic and socio-material relations that modify and attribute (new) agential capacities to Filipino coffee farmers. The study highlights the tensions that occur between farmers and community stakeholders, and the multiple lines of market action that farmers pursue as a result of agencing. Despite the best intentions and efforts of community stakeholders to help these farmers, the findings reveal a number of misfires, which partially disabled farmers' agency and negatively affected their newly emerging market relations. By highlighting the role of human and nonhuman actors in agencing processes, this study responds to the critique of current development strategies that portray agency (and the lack of it) as the individual capacity of the poor. The findings of this study advance research in the field of Market Studies by illuminating both the underemphasized human side of agencing and the obscured role of agenced, disadvantaged market actors in shaping markets.

Air pollution is the single largest environmental health risk worldwide. Exposure to the most harmful component of air pollution, particular matter (PM), has been linked with non-communicable diseases including chronic obstructive pulmonary disease (COPD) - the third leading cause of death worldwide. Exposure to PM is one of the biggest risk factors for COPD disease exacerbations, that are frequently linked with bacterial infection by Haemophilus influenzae and Moraxella catarrhalis. Whether infection is a cause or consequence of disease exacerbations remains unclear. It has been shown that behaviour of Staphylococcus aureus and Streptococcus pneumoniae is directly impacted by exposure to PM, which could be significant for COPD patients, with disease decline being linked to PM exposure and bacterial infection. The purpose of this study was to elucidate the effects of PM on H. influenzae and M. catarrhalis. H. influenzae that were exposed to black carbon (BC) showed a significant iron-uptake response, potentially linked with the observed increase in epithelial cell adhesion through the upregulation of protein F, that is known to facilitate binding to respiratory epithelium. The ability of PM to cause significant changes to bacterial behaviour was also demonstrated by the stress response exhibited by M. catarrhalis. Heat shock proteins regulated by sigma factor 32 were upregulated when exposed to BC, showing the potential of PM to influence specific genetic regulators. Also in this thesis, the relationship between respiratory microbiome commensals and pathogens on the integrity of the respiratory epithelium was explored. Prevotella spp. abundance has been linked with markers of epithelial integrity in COPD patient populations, while M. catarrhalis has been linked with disease decline and increased inflammation. The potential beneficial properties of Prevotella spp. on epithelial integrity were explored using a model of respiratory epithelium, finding that P. melaninogenica has a weaker potential to damage epithelial integrity than M. catarrhalis.