VictorJuiz/thesis huggingface dataset:
The doctor-patient relationship and encounter in the nineteenth-century French novel

This thesis investigates the representation of the doctor-patient relationship and encounter in the nineteenth-century French novel. It incorporates and compares a number of authors, most notably Honoré de Balzac, Jean-Jacques Rousseau, George Sand, Stendhal, and Émile Zola, as well as contemporary medical treatises and theses. Using a historicist approach to inform literary close readings, this thesis recreates the medical and scientific discourse which surrounded the nineteenth-century novel. It argues that the doctor-patient relationship and encounter can be understood as a way that the nineteenth-century French novel gains traction on contemporary medicine, since both foreground the extent to which medicine was understood as an art and practice as well as a science. The thesis argues that the difference between doctor-patient relationship and encounter was particularly useful for authors of the period. The doctor-patient relationship represents an ideal form of medicine; whereas the bedside medical encounter, as depicted in literature, offers readers a more dissonant conception of medicine. I argue that the doctor-patient relationship and encounter narrativize medicine in the nineteenth-century novel, allowing authors to present and interpret medicine as embedded within narrative. The doctor-patient relationship and encounter are particularly useful for the development of plot and characterization, despite or indeed because of the medical plot’s peripherality to the novel. This thesis is not restricted to any singular field of medicine; it encompasses themes such as the figure of the country doctor, the history of gynaecology, tuberculosis, cholera, hysteria, and the medical authorisation of miracles. The thesis concludes with a discussion of monetized medical relationships. Overall, this thesis demonstrates that the doctor-patient relationship and encounter, and in particular the cleavage between them, is key to understanding the representation of contemporary medicine and science by the nineteenth-century French novel.

Keywords: doctor-patient encounter
doctor-patient relationship
medicine
nineteenth-century French novel
science
Advisor: Manzini, F
Commercial determinants of health: how do they shape health policy and the consumption of unhealthful commodities?

This thesis is about the role that commercial interests, such as multinational corporations, play in driving the consumption of unhealthful commodities such as tobacco and alcohol. The focus is on the role that health policy, namely tobacco and alcohol control policy, plays in mediating any positive association that may exist between the power of these commercial interests and the prevalence and/or incidence of tobacco and alcohol consumption.
To investigate these associations, I built a novel measure of corporate power – the Corporate Permeation Index. I then use it to explain variations in the consumption of tobacco and alcohol as well as variations in the quality and/or comprehensiveness of the regulatory framework for these commodities. I also use it to quantify the interaction between state interventions such as monopolies on alcohol production and/or retail and corporate power and how the former may curb the capacity of the latter to boost alcohol consumption. Finally, I address the question of whether these associations differ by country income level. The rationale is that countries with fewer economic and human resources may be more vulnerable to corporate power and thus to weaker formulation and implementation of evidence-based health policy.
I find that that corporate power is associated with higher prevalence of smoking and drinking and with weaker policy packages. I also find that the protective effect of public health policy varies according to income level but not for both substances.
My findings suggest that there is a role for evidence-based public health policy in reducing the prevalence and the incidence of risk behaviours and in weakening the associations between corporate power and the adoption of these behaviours. While state interventions such as government monopolies seem to be associated with lower alcohol consumption at all income levels, tobacco control policy seems to be less effective at lower income levels. This finding suggests that more resources could be devoted to assist countries with fewer resources to improve tobacco control policy implementation.

Advisor: Fisher, S
Galea, S
Pastor Tillich: the justification of the doubter

This dissertation is a study of Paul Tillich’s early theological development from his student days until the end of the First World War, set against the backdrop of church politics in Wilhelmine Germany and with particular reference to his early sermons. The central questions are: Where did Tillich ‘land’ theologically after the war? And how did he get there?
The project offers a different focus from the majority of Tillich scholarship which understands Tillich primarily as a philosophical theologian. For before and during the First World War, Tillich was Pastor Tillich. Notwithstanding his philosophical study and academic ambitions, in the period 1904–18 he was studying theology to become a pastor, leading a Christian student group, working periodically as a pastor in Berlin churches, and preaching to soldiers. Through exposition of Tillich's early sermons, the pastoral context of his early thought becomes clear.
Alongside the chronological boundary of 1919, the account is limited to one central theme, Tillich’s notion of the justification of the doubter. In 1919 Tillich wrote an essay, Rechtfertigung und Zweifel [Justification and Doubt], for the faculty in Berlin, claiming the main problem of his systematic thought was the religious dialectic of doubt. This 1919 essay is compared with Tillich’s writing across genres before and during the First World War.
The influence of Schelling on Tillich’s theology is well established. This dissertation also explores the role of Søren Kierkegaard, Ernst Troeltsch, Martin Kähler, Wilhelm Herrmann, Wilhelm Lütgert, Fritz Medicus and Tillich’s father Johannes Tillich, distinguishing between Tillich’s later autobiographical statements and the witness of archival sources.
Drawing on material largely unknown to English-language scholarship, this chronologically and thematically focused dissertation on the issue of doubt in Tillich’s early theology offers a significantly original, contextualised account of Tillich’s early life in Germany. It should therefore be of interest not only to Tillich scholars, but to any interested in the history of modern theology, as an example of how biography and theology are intertwined.

Keywords: theology of Paul Tillich
doctrine of justification
modern German theology
Advisor: Rasmussen, JDS
‘We are the nobodies': youth violence, marginality and social cleansing in Colombia

Colombia’s ‘transition to peace’ faces various challenges. One is the activity of drug- related criminal organisations, which use adolescents to carry out low-level tasks. Based on 18 months of ethnographic fieldwork, this thesis explores the lives and perspectives of a group of adolescents who are starting to engage in criminal activities and the violence associated with them in the town of San Carlos and in the close-by city Medellín. Informal conversations with these youths and regular observation of their activities, as well as engagement with their families and communities, reveal aspects of their lives that mainstream discourses and statistics about violence cannot account for. The central question I ask is why and how some youths engage in organised crime and violence, despite the enthusiasm for peace currently permeating their country. I propose that these youths’ involvement in crime and violence is shaped by the precarity and ontological insecurity that characterise their lives. First, this thesis describes the process whereby these youths are progressively marginalised and come to be conceived as worthless and killable, through a number of practices ranging from stigmatisation and corporal punishment to police harassment and social cleansing. It then explores how they react to marginalisation by both embracing an oppositional identity and striving to overcome it. Having been made to feel like ‘nobodies’, they see joining a criminal group as the only way of ‘becoming somebody’, in social, economic and moral terms. However, I also show that the process of deciding to engage in crime and violence is experienced with a great deal of ambivalence and hesitation, as evidenced by these youths’ contradictory moral discourses about violence. By contextualising these findings within Colombia’s political juncture, this thesis questions clear-cut distinctions between conflict and its aftermath, and points towards further transformations that need to take place for peace to last.

Keywords: Colombia
Violence
Crime
Latin America
Youth
Social Cleansing
Marginality
Advisor: Pirie, F
Mechanism employed by germinal centre B cells for promoting affinity maturation

The adaptive immune system has the extraordinary ability to develop bespoke antibodies against almost any invading agent to which the host may be exposed. These antibodies are produced through affinity maturation, a dynamic process of iterative diversification and refinement. This process occurs in germinal centres (GCs), microanatomic loci physically divided into dark zones (DZs), in which the immunoglobulins are diversified though somatic hypermutation (SHM), and light zone (LZs), in which cells are selected such that the population can be refined. Accurate selection requires that cells fully replace surface B cell receptors (BCRs) following SHM, but whether this happens before LZ entry is not clear. We found that most GC B cells degrade pre-SHM receptors before leaving the DZ, and that B cells acquiring crippling mutations during SHM rarely reached the LZ. Instead, apoptosis was triggered preferentially in late G1, a stage wherein cells with functional BCRs re-entered cell cycle or reduced surface expression of the chemokine receptor CXCR4 to enable LZ migration. Ectopic expression of the anti-apoptotic gene Bcl2 was not sufficient for cells with damaging mutations to reach the LZ, suggesting that BCR-dependent cues may actively facilitate the transition. We postulated that a BCR mediated signal may be required as a “LZ promoting cue”. Thus, BCR replacement and pre- screening in DZs prevents the accumulation of clones with non-functional receptors and facilitates selection in the LZ.

Advisor: Bannard, O
Cornall, R
Neither local nor global: a political ethnography of storytelling and norm diffusion in the UNDP China

This dissertation examines the practice of storytelling in norm diffusion based on an in-depth political ethnography of the United Nations Development Programme (UNDP) in China. Closely engaging with glocalisation literature, this dissertation focuses on the manner in which non-linear and multidirectional norm diffusion that disrupts, fractures and transcends the local-global opposition, creating entanglements across layers of orders and scripts. Norm translators are the main actors in the mediation and communication of reframing and relocating normative packages. Empirically, this dissertation addresses the insufficient attention paid to the everyday micro-dynamics of norm diffusion, and particularly how norm circulation and contestation unfold and intensify in the context of emerging powers. The UNDP China office thus serves as an ideal case to study how such practices and processes unfold over time. My methodological approach is political ethnography, employed through a period of intensive fieldwork and participant observation carried out from 2015 to 2018, when my work at the UNDP allowed unparalleled access to materials and the internal organisational processes.
My fieldwork experience highlights the critical role played by stories in translating and appropriating norms. Drawing on the theories of in-between storytelling in institutional contexts, this dissertation argues that an internalisation process of “norm metamorphosis” translates original norms into textual realities, projects and stories. These stories are normative, canonical, ambiguous, open to interpretations, and used as persuasion instruments. Detailed case studies then demonstrate the emergence and application of stories in human rights, rule of law and development cooperation. The content, form and audience of the stories are shaped by issue characteristics and ideological backgrounds, bearing the hallmarks of UNDP officials and local actors. The dissertation further describes how local norms return to the global stage through the UNDP’s narration of China’s development experience. Instead of reinforcing the local-global opposition, these stories carve out intermediary and liminal spaces through which concepts and ideas travel and transform, redefining the identity of international organisations and transnational networks in recursive conversations.

Advisor: Thornton, P
Improving outcomes for resistant rectal cancer

The management of locally advanced rectal cancer involves the use of neoadjuvant chemoradiotherapy but up to 20% of patients have no discernible response. Understanding the factors that mediate resistance to treatment is therefore an important clinical research question. The work in this thesis aimed to further understand potential biological contributors to therapeutic resistance by exploring the contribution of the KEAP1-NRF2 pathway in-vitro and evaluating it as a potential biomarker in-vivo.
Using RNAi and clonogenic assays, NRF2 knockdown produced a radiosensitive phenotype in intrinsically resistant cell line models but had no effect in the most radiosensitive cell line. An attempt at CRIPSR isogenic validation of the RNAi was also made. Using a CRISPR isogenic activating mutation, radioresistance was induced in this previously sensitive cell line. Overexpression of NRF2 also induced chemoresistance to the commonly used radiosensitizers in clinical practice.
RNA sequencing was carried out on both NRF2 downregulated (radiosensitive) and NRF2 upregulated (radioresistant) cell line models to better understand the mechanism of radioresistance. NRF2 downregulation produces a marked reduction in amino acid metabolism, particularly glutamine/asparagine, relative to control conditions. Overexpression of NRF2 produced the opposite effect. The data suggest an NRF2 regulated ‘switch’ of metabolism in favour of an anabolic, proliferative phenotype which produces radioresistance.
To understand the clinical relevance of NRF2 signalling a bioinformatic approach was used. A metagene signature of 36 NRF2 regulated genes to aggregate pathway expression was derived and trained using publically available datasets. The resulting transcriptomic biomarker demonstrated that high NRF2 expression was associated with worse survival outcomes in 1,360 validation patients from public resources and the S:CORT collaboration. Interestingly NRF2 expression was significantly enriched in Consensus Molecular Subtype 4, suggesting a further refinement of the molecular transcriptomic classification of colorectal cancer.
Lastly higher NRF2 expression was shown to be associated with a worse response to neoadjuvant chemotherapy, as measured by the neoadjuvant rectal score, in a curated cohort of 127 rectal cancers who received standard of care treatment. This validates the in-vitro cell line findings and supports an important role for NRF2 signalling in prognosis and therapeutic resistance in colorectal cancer.

Keywords: radiation
rectal cancer
Advisor: Maughan, T
Hawkins, M
Lewis, A
Variability in gamma-ray sources

Gamma-rays are known to be emitted from some of the most extreme sources in the known Universe. Many of these objects are volatile and variable, and understanding them is the focus of the work contained in this thesis.
One such class of objects which are highly variable in gamma-rays are blazars, which are known to be variable on ∼ minute timescales at TeV energies. We present a macroscopic emission model to investigate whether magnetic reconnection is a feasible mechanism which can cause this rapid variability, assuming the primary emission mechanism to be synchrotron self-Compton (SSC). We show that in this case reconnection produces synchrotron-dominated flares so in general cannot fit broadband observations, although rapid flares can be produced.
Underlying physical processes occurring in astrophysical sources are believed to relate to the functional forms of the probability distribution function (PDF) of their time-series. Gaussian and lognormal PDFs correspond to linear and multiplicative processes, respectively. By simulating artificial light curves of known PDF functional forms, we prescribe a method for calculating the likelihood that the PDF has been correctly measured, applying this to the blazar PKS2155-304.
In recent years, observations made using the Fermi Large Area Telescope (LAT) have revealed classical novae (CNe) as gamma-ray sources, yet not every optically discovered CNe is a gamma-ray source. Here, we present simulations of an artificial Milky Way population of CNe with optical properties based of those detected in M31 and gamma-ray properties based on the observed sample. We show that observations are consistent with all CNe being gamma-ray sources and predict that all CNe at distances <8 kpc will be detected in gamma-rays.

Advisor: Cotter, G
Potter, W
Pan-genomic analysis of clonal bacterial samples using nanopore reads and genome graphs

Bacterial genetic variation originates through multiple mechanisms, including mutations during replication, movement of mobile elements, and various forms of recombination. As a result, genomes can be highly divergent with only a small fraction of genes core to all and a large pangenome of genes which have been identified in one or more sequenced samples.
In this context, the ability to accurately detect genetic variation throughout the pangenome and compare many genomes remains a difficult problem. Here we present a novel pangenome reference graph structure, which represents the known genetic variation within a species as a collection of `floating' graphs. Each of these represents some homologous region such as a cluster of genes. By approximating a sequenced genome as a mosaic of genomes from the reference panel, this design forms the basis for a systematic framework in which to analyse diverse sets of samples where a single reference would be inappropriate.
Applying this method to E. coli, we demonstrate how it enables us to describe genetic variation at both a coarse (gene presence) and a fine (SNP/indel) level. We demonstrate how this enables us to successfully compare divergent genomes within a species, gaining dramatically higher sensitivity to SNP variation than single reference-genome approaches. We go on to demonstrate how this method enables us to investigate global genetic variation in K. pneumoniae, and to describe the spectrum of allele frequencies in accessory genes.
The method works for either long Nanopore or short Illumina reads, and we hope will provide the basis for addressing many questions in diverse datasets.

Keywords: Reference graphs
Nanopore
Pangenome
Advisor: Iqbal, Z
Crook, D
Probabilistic inference for dynamic networks and complex event processes

This thesis introduces new unsupervised machine learning algorithms for complex event data. Event data---records of things that happen---is both ubiquitous and abundant in the modern world. Many types of event occur when two or more distinct entities interact. If these entities are capable of interacting with other entities, the result is typically a network of interactions that is dynamic and complex.
One very general statistical model of events is a Poisson process. In this work, Gaussian processes---another statistical model---are used to modulate the intensity of Poisson processes allowing dynamic patterns of interactions to be captured. This dynamic model can then be further extended using latent variables that represent the missing information needed to unpick the complex interactions present in the data. Learning Bayesian posterior distributions of the latent variables reveals previously hidden structure and also allows statistical strength to be shared across multiple distinct event streams, improving predictive performance.
Efficient inference in these models is challenging however, and a significant contribution of this thesis is an efficient Bayesian inference algorithm for Gaussian process modulated Poisson processes. This scheme scales linearly in the number of observed events and does not require discretisation of the input domain, or expensive Monte-Carlo simulation, that previous posterior inference algorithms for this model required. Latent variable adaptations of this model are presented and the resulting algorithms are applied to data from a variety of different application domains.

Advisor: Roberts, S
Computational insights into organic and organometallic catalysis

This thesis presents computational studies of some catalytic systems in both organic and organometallic chemistry using density functional theory (DFT). With these studies, we show how electronic structure theory such as DFT can complement experimental studies in elucidating and unravelling complex mechanisms. In Chapter 1, we give an overview of the theoretical background governing computational quantum chemistry and electronic structure theories. We then look at how theory is translated to the quantitative study of chemical reactivity and selectivity through simple transition state theory. Chapters 2 and 3 look at organocatalysis. In Chapter 2, we discuss computational work on the oxidant-promoted, hole-catalysed cyclobutanation between two unsymmetrical olefins (Scheme 0 (a)). Chemoselectivity (of reacting olefins), regioselectivity and stereoselectivity (of product formations) were explored. Chapter 3 discusses the mechanistic investigation of a novel bifunctional hydroxyphosphine catalyst, coupling with terminal phenylsilane reductant, in catalytic Staudinger reduction of azide to amine (Scheme 0 (b)). Chapters 4 to 7 look at the catalytic C–H bond functionalisations using transition-metal catalysts. In Chapter 4, we discuss Pd-catalysed δ-selective C(sp3)–H arylation of α-amino acids (Scheme 0 (c)). In Chapter 5 and Chapter 6, we look at the mechanisms underlying Pd-catalysed meta-selective C(sp2)–H allylation using unbiased internal olefin as an allyl surrogate and alkynylation via inverse Sonogashira coupling using trialkylsilylated bromoalkyne, respectively (Scheme 0 (d)). In Chapter 7, we look at using different transition metal catalysts to effect the regiodivergent C(sp2)–H arylation of isoquinolone (Scheme 0 (e)). Chapter 8 gives some concluding remarks regarding the field of computational chemistry in organic and organometallic catalyses and some outlook to the future of chemistry using other computational tools apart from those used in this thesis.

Keywords: catalysis
mechanisms
Density functional theory (DFT)
theoretical investigations
Advisor: Paton, R
McGrady, J