VictorJuiz/thesis huggingface dataset:
Faithful but flexible: Intervention fidelity in clinical trials of complex interventions in healthcare

The focus of clinical trials is typically interventions’ efficacy, or whether they attain their desired outcomes. Comparatively less attention is focused on understanding how or why interventions succeed, or fail to attain, those outcomes. This may be particularly important in trials of complex interventions such as surgery or physiotherapy, which are multifaceted and often tailored to individual participants, providers, or settings, increasing the potential for variations in intervention delivery and effects.
The correspondence between the intervention that was planned and what was actually delivered in a trial is the intervention’s fidelity. Several benefits for high levels of intervention fidelity have been proposed. However, whether or how much fidelity influences clinical trials’ treatment effect estimates had not previously been determined. A lack of a uniform definition for fidelity and its key components may also hinder intervention delivery in clinical trials and the translation of evidence-based interventions to clinical practice.
The principle aim of this thesis was to investigate the effects of intervention fidelity on the results, interpretation, and appropriateness to change practice of clinical trials of complex interventions. Through systematic review, “Best-fit” framework synthesis, reliability study, meta-epidemiological study, and fidelity assessment in an on-going pragmatic randomised controlled trial (RCT), it addressed several important knowledge gaps for intervention fidelity in complex intervention clinical trials. It estimated the prevalence of fidelity monitoring and reporting in complex intervention RCTs. It contributed an empirically-based intervention fidelity framework and a reliable, internally consistent fidelity assessment checklist tailored to the unique needs of researchers who seek to assess clinical trials in rehabilitation. It also estimated empirically, for the first time, the magnitude and direction of bias in treatment effect estimates arising from poor intervention fidelity in rehabilitation RCTs. Fidelity assessment in the ACL-SNNAP trial also provided new insights into the feasibility, applicability, and impact of monitoring intervention fidelity and participant adherence in complex intervention pragmatic trials.
The findings of this thesis showed that intervention fidelity is important, not just on a theoretical, but also on an empirical level. This thesis provides new and important information for the conduct and interpretation of clinical trials in rehabilitation and other complex interventions in healthcare.

Keywords: treatment effects
evidence-based medicine
surgery
meta-epidemiological
Intervention fidelity
treatment effect estimates
bias
treatment fidelity or treatment adherence
Clinical trials
randomised clinical trials
compliance
rehabilitation
complex interventions
Adherence
Advisor: Beard, D
Davidson, P
McCulloch, P
The role of cooperation in bacterial ecology and evolution

Bacteria can perform a range of cooperative behaviours, yet the significance of these cooperative behaviours in bacterial ecology and evolution is a burgeoning research area. In this thesis, I use a comparative genomics approach to elucidate the impact of cooperation on bacterial ecological and evolutionary processes. Specifically, I: (i) probe the effects of cooperation on the evolution of bacterial niche breadth; (ii) investigate the relationship between horizontal gene transfer and bacterial cooperation, with a specific emphasis on the interplay between gene connectivity and sociality in determining gene transfer potential. Additionally, I expand the scope by examining how ecological determinants and genomic characteristics shape the evolution of bacterial growth rates. In summary, this thesis offers novel perspectives on bacterial ecology and evolution through the lens of bacterial cooperation.

Keywords: comparative genomics
horizontal gene transfer
microbial ecology and evolution
becterial cooperation
Advisor: West,S
Ghoul, M
Investigating the role of human microglia in tau pathogenesis

In neurodegenerative diseases collectively known as tauopathies, the microtubule-associated tau protein aggregates into insoluble deposits. Tau deposits propagate along synaptically- connected brain regions in a prion-like manner, correlating with disease progression and severity. Genetic studies have recently implicated perturbations in phagolysosomal clearance by microglia, the major brain-resident phagocytes, as a key candidate mechanism driving tau pathology. However, functional studies elucidating the precise mechanisms in a relevant model of human microglia are missing.
In this thesis, I have developed an efficient protocol for purification and in vitro aggregation of endotoxin-free, human recombinant tau. I then used an authentic, in vitro model of human microglia - induced pluripotent stem cell-derived (iPSC)-macrophages and microglia - to characterise microglial responses to tau at functional level, including tau uptake, degradation, and secretion, as well as prion-like behaviour of the microglia-processed tau. I have identified Low Density Lipoprotein Receptor-Related Protein-1 (LRP1) as major receptor mediating tau entry to microglia. I further found that the internalised soluble tau is readily degraded by microglia but intracellular clearance of aggregated tau is concentration- and incubation-length dependent, and inversely associated with microglial tau release. Tau fibrils processed by microglia retain seeding competency, thus supporting the putative role for microglia in tau prion-like spreading.
In addition, I present a novel finding that Leucine-Rich Repeat Kinase 2 (LRRK2), a candidate genetic determinant in Parkinson’s disease (PD) and Progressive Supranuclear Palsy (PSP) tauopathies, influences microglial cargo clearance pathways and tau-specific processing. Specifically, my results show that the PD- and PSP-associated G2019S LRRK2 mutation enhances iPSC-macrophage baseline proteolytic activity, tau uptake, clearance, and possibly prion-like activity of the non-cleared tau species accumulating within the cells.
Collectively, this thesis supports the putative role of microglia in tau pathogenesis and provides further reasoning for investigating microglia-enriched tauopathy risk variants as potential druggable targets.

Keywords: iPSC-microglia
tau
prion-like tau transmission
Advisor: James, W
Cowley, S
Structural study of enteroviruses

Enteroviruses comprise a genus of picornaviruses causing global morbidity and regional outbreaks. These viruses are the causative agents of severe, widespread diseases such as hand-foot-and-mouth disease, poliomyelitis and aseptic meningitis. Although they have been studied for decades, few vaccines or drugs are in use. Indeed, many structural details of enterovirus infection, immune response and life cycle remain unknown. Solving these structural mysteries may provide crucial information that aids the elimination of these infectious particles.
The work described in this thesis extends our structural understanding of enteroviruses detailing the receptor binding manner of Echovirus 11 and closely related enteroviruses (chapter 3) and the polyclonal antibody response to poliovirus (chapter 4). To support these studies, a ‘SyRe’ protocol is described for analysis of enterovirus capsid proteins at protomer-scale, and pentamer-scale for the efficient detection of polyclonal antibody attachment (chapter 4). Finally, an in-vitro host cell membrane mimetic system is optimized to visualize virus-cell attachment and membrane penetration (chapter 5), together with powerful EM tools this will facilitate obtaining detailed structural information of virus entry in the near future.

Advisor: Stuart, D
Fry, E
The archive, time and the body in refugee writing in Arabic and English

This thesis contributes to the ‘new field in literary studies’ (Potter and Stonebridge 2014:1) denominated ‘Refugee Writing.’ Inter alia, this burgeoning field critiques the typology of suffering which has often marred writings about refugees (Farrier 2011), whilst also acknowledging the challenges of perceiving such literatures as a means of eliciting a ‘literary humanitarian’ impulse amongst its readers (Rickel 2018:97). Through centralising the agency of refugees, as responders to their own lives and those of others, and through exploring complex configurations of ‘refugee-refugee relationality’ (Fiddian-Qasmiyeh 2015), I argue that the selected texts push against the assumption that the main form of tension (and thus of resolution) is framed around refugee-citizen relations. By centralising refugees’ own archival practices, their roles as time-makers, and refugees’ potential to engender ‘a different writing of embodiment’ (Ahmed 1998:64), I posit that the texts under study – Ghassan Kanafani’s Rijāl fī al Shams (Men in the Sun) (1962), Salim Barakat’s Hiyāj al-Iwazz (Rampaging Geese) (2010), Abdulrazak Gurnah’s By the Sea ([2001] 2002) and Claire Bayley’s The Container (2007) – destabilise traditional frames of reference which position the citizen as the quintessential observer of and responder to displacement. In particular, by identifying and examining the processes of writing and reading that emerge within the selected texts, I seek to advance a shift in contemporary literary studies by positing the significance of complementing an analysis of ‘refugee writing’ with the concomitant process of ‘refugee reading.’ In addition to intervening in discourses concerning refugees, refugee literature and refugee studies, my thesis equally offers a wider contribution to key debates concerning the politics of knowledge production; intimate archiving processes contra traditional historiographies and archives; and the agency of minoritized individuals and communities in contexts of structural inequality and violence.

Keywords: archive
Ghassan Kanafani
postcolonial literatures
time and temporality
refugee body
refugee studies
Salim Barakat
Claire Bayley
literatures of the South
decolonial theory
production of knowledge
Rampaging Geese
refugee literature
The Container
comparative literature
refugee writing
By the Sea
Men in the Sun
counter-archive
Abdulrazak Gurnah
containment
refugee reading
body and embodiment
Advisor: Reynolds, M
Omri, M
Studies of five dimensional superconformal field theories, localization and geometry

In this thesis, we study the U-plane of rank-one 5d N = 1 superconformal field theories (SCFTs), which is the one-dimensional Coulomb branch (CB) of such theories on R4×S1
. This circle compactification gives us 4d N = 2 supersymmetric field theories of ‘Kaluza-Klein (KK) type’, and thus the Coulomb branch physics can be described by its Seiberg-Witten (SW) geometry. The total space of the SW geometry, which consists of the SW curve fibered over the CB, can be modelled as a rational elliptic surface. As such, a classification of all possible Coulomb branch configurations, for the 5d field theories and their 4d descendants, is given by Persson’s classification of rational elliptic surfaces. This formalism trivializes renormalization group flows, while also containing information about the global form of the flavour symmetry group and the one-form symmetry, through the Mordell-Weil group of the SW geometry. Moreover, in a number of important instances, the U-plane is a modular curve, and we use its beautiful modular properties to investigate aspects of the low-energy physics, such as the spectrum of light particles at strong coupling and the associated BPS quivers.
A related approach to studying the strong-coupling dynamics of these theories is to consider them on curved backgrounds M5. Our focus is on closed five-manifolds M5 which are principal circle bundles over simply-connected K\"ahler four-manifolds, M4
. Starting with the topologically twisted 4d N = 2 KK theory on M4
, we propose a new approach to compute the supersymmetric partition function on M5
through the insertion of a fibering operator in the 4d theory, which introduces a non-trivial fibration over M4
. We determine the so-called Coulomb branch partition function on any such M5
, which is conjectured to be the holomorphic ‘integrand’ of the full partition function. We precisely match the low-energy effective field theory approach to explicit one-loop computations, and we discuss the effect of non-perturbative 5d BPS particles in this context. When M4
is toric, we also reconstruct our CB partition function by appropriately gluing Nekrasov partition functions.

Keywords: supersymmetric localization
Seiberg-Witten geometry
superconformal field theories
Advisor: Closset, C
Schäfer-Nameki, S
A techno-socioeconomic investigation of the Husi kiln complex in the middle Yangtze River Valley

This thesis presents an initial investigation of the Husi kiln complex (Husi), a significant yet understudied archaeological site in the middle Yangtze River valley. By examining the archaeological background, sociohistorical context, nature of production, geological context, and distribution of ceramics associated with Husi, this research aims to enhance our understanding of its role in the broader regional context of ceramic production in China.
One of the contributions of this research is the critical analysis of the – so far fairly limited – previous studies on Husi, identifying gaps in our knowledge and providing a foundation for subsequent research. By synthesizing the findings from these studies, this thesis offers a holistic understanding of Husi, its role in the ceramic industry, and its impact on the socio-economic and cultural landscape of the region during its period of operation.
This study then advances our understanding of this understudied sight significantly by investigating the nature of ceramic production at Husi through bulk chemical and microstructural analyses on a diverse range of ceramic samples. The exploration of the geological context of Husi is another important aspect of this research. By conducting archaeological fieldwork surveys and collecting geological samples, this study provides crucial insights into the characteristics and properties of the raw materials used in ceramic production at Husi. This understanding is further deepened through replication work, which sheds light on the production processes employed.
Moreover, this thesis contextualizes Husi within the broader regional production and distribution of ceramics through a comparative analysis with other prominent kiln sites, particularly the Jingdezhen kiln, across different periods. This comparative approach elucidates the role and contributions of Husi to porcelain production at the time and provides a deeper understanding of the unique aspects and characteristics of each site. Additionally, this study identifies shared trends, technological changes, and stylistic developments across the broader ceramic industry, as well as the specific factors that contributed to the success or decline of each kiln complex.
Overall, this thesis significantly enriches the current understanding of Husi by situating it within a broader context and shedding light on its unique contributions to the ceramic production history in China. The study's findings are expected to be of interest to scholars and researchers in the fields of archaeology, art history, and cultural heritage, enriching the current knowledge of Husi's historical and cultural significance.

Keywords: geochemical analysis
archaeological field work
experimental archaeology
Middle Yangtze River Valley
Husi kiln complex
Advisor: Hein, A
Doherty, C
On designing an algorithmically enhanced NHS: towards a conceptual model for the successful implementation of algorithmic clinical decision support software in the National Health Service

Established in 1948, the National Health Service (NHS) has lasted 75 years. It is, however, under considerable strain: facing chronic staff shortages; record numbers of emergency attendances; an ambulance wait-time crisis; and more. Increasingly, policymakers are of the view that the solution to these problems is to rely more heavily on one of the NHS’s greatest resources: its data. It is hoped that by combining the NHS’s data riches with the latest techniques in artificial intelligence (AI), that the means to make the NHS more effective, more efficient, and more consistent, can be identified and acted upon via the implementation of Algorithmic Clinical Decision Support Software (ACDSS). Yet, getting this implementation right will be both technically and ethically difficult. It will require a careful re-design of the NHS’s information infrastructure to ensure the implementation of ACDSS results in intended positive emergence (benefits), and not unintended negative emergence (harms and risks). This then is the purpose of my thesis. I seek to help policymakers with this re-design process by answering the research question ‘What are the information infrastructure requirements for the successful implementation of ACDSS in the NHS?’. I adopt a mixed-methods, theory-informed, and interpretive approach, and weave the results into a narrative policy synthesis. I start with an analysis of why current attempts to implement ACDSS into the NHS’s information infrastructure are failing and what needs to change to increase the chances of success; anticipate what might happen if these changes are not made; identify the exact requirements for bringing forth the changes; explain why the likelihood of these requirements being met by current policy is limited; and conclude by explaining how the likelihood of policy meeting the identified requirements can be increased by designing the ACDSS’s supporting information infrastructure around the core concepts of ‘utility, usability, efficacy, and trustworthiness’.

Keywords: ethics
information infrastructure
design
NHS
artificial intelligence
healthcare
clinical decision support software
Advisor: Floridi, L
Taddeo, M
Essays in decision-making and organizational behaviour in public bureaucracies

Public servants, no matter how carefully they are selected or incentivized, are only imperfectly able to discharge the objectives of the organizations they work for. They may suffer from bounded rationality, or make systematically biased decisions. They may be pursuing goals at odds with the stated or implied organizational mandate. Or they may suffer from low engagement in their work, and be difficult to retain over time. Through three quantitative essays, I examine how decisions are made in public sector organizations, and in particular how the behaviour of agents who vary in their ability, motivation and the incentives they are responding to contribute to public service (dys)function. In my first paper, a survey experiment in a large UK public sector organization, I find exposure to politician preferences (orthogonal to organizational mandate) increases the rate at which junior decision-makers provide advice contrary to the evidence they are provided with, but no such effect is found for senior officials. In my second paper, an observational study drawing on a large and novel dataset on projects implemented by the same organization, I show that a peer review process induced substantial avoidance of the system around the threshold for eligibility, but available metrics of project quality show only weak evidence of an effect around this threshold. And in my third paper, I use a survey experiment with a sample of public servants from 28 countries to investigate the effect of varying the framing of the gains to organizational initiatives on likelihood of participation, finding few overall effects but some heterogeneity according to pre-existing variation in public servant characteristics. These three papers have implications for how public organizations should structure their work.

Keywords: organizational behaviour
bureaucracy
public organization
Advisor: Dercon, S
Generation of 12-lead patient-specific electrocardiogram and risk prediction of cardiovascular disease using deep learning

This thesis presents a novel deep learning framework based on Variational Autoencoders (VAEs) for the generation and analysis of 12-lead electrocardiograms (ECGs), and its use for cardiovascular disease (CVD) risk prediction. It focuses on three major aspects:
First, we propose a model for 12-lead ECG generation that is capable of generating realistic 12-lead ECG data. Comparison with existing methods shows that ours produces lower Maximum Mean Discrepancy and more lead information, while maintaining generation diversity. The model provides an interpretable latent space to explain the generation process and allows for a deeper understanding of the relationships between ECG features.
Second, we introduce patient-specific characteristics by extending the VAE to a conditional VAE, incorporating essential subject-specific information such as age, sex, Body Mass Index (BMI), and anatomical properties of heart and torso into the ECG generation process. This integration enables our model to generate ECGs that are representative of subjects with diverse profiles. The generated ECGs demonstrate strong correspondence with established models and in-silico experiments. To the best of our knowledge, our model is the first deep learning method to integrate heart information into ECG generation. This brings the potential to improve personalized medicine and contribute to a better understanding of the relationship between heart anatomy and ECG morphology.
Lastly, we focus on future cardiovascular disease risk prediction by leveraging the latent space derived from the VAE. We develop an additional classifier that effectively stratifies patients into low and high-risk groups for CVD. This finding shows the presence of informative ECG features for CVD prediction and demonstrates our model’s ability to extract these features, offering new insights for early CVD risk detection and prevention.
In summary, this work contributes to the growing body of research exploring the potential of deep learning techniques in electrocardiography, and their implications for personalized medicine, improved diagnostics, and early CVD risk detection. The proposed VAE-based framework serves as a robust and versatile tool for advancing the field of ECG analysis and risk prediction.

Keywords: ECG generation
variational autoencoder
cardiac MRI
risk prediction
electrocardiogram
Advisor: Grau Colomer, V