VictorJuiz/thesis huggingface dataset:
Estimation of Plasmodium falciparum allele and multi-SNP haplotype and genotype frequencies

Malaria kills hundreds of thousands of people each year, yet is entirely curable given prompt treatment. Malaria parasites evolve resistance to antimalarial drugs, hence routine surveillance of antimalarial resistance is vital. The surveillance of parasite genetic markers of resistance provides an economical adjunct to clinical efficacy trials, and has the potential to resolve drug specific resistance ahead of clinical failure. To monitor spatiotemporal changes using genetic markers, frequencies of alleles and/or haplotypes and genotypes spanning multiple single nucleotide polymorphisms (SNPs) are required. However, multiclonal infections complicate frequency estimation, especially in highly endemic regions.
With the aim of harnessing the full potential of genetic markers for the surveillance of antimalarial resistance, a statistical model to estimate frequencies is proposed. The model builds upon existing methods (reviewed in chapter 2), without reliance upon experimentally-derived estimates of the sample-wise multiplicities of infection (MOIs). Its ability to generate precise and accurate estimates within a Bayesian framework is documented in chapter 3. In chapter 4, the model is applied to data collected from a cohort of children enrolled in a longitudinal trial in Uganda, generating valuable insight into haplotype frequency trends. In chapter 5, the model is extended to investigate inter-child variability in the aforesaid cohort, revealing a small amount of inter-child variation. In chapter 6, the model is modified to enable the analysis of short-read sequencing data, with application to data from malaria patients in Northern Ghana, providing insight into the extent of within-host diversity and anti-folate resistance in the region.
In summary, this thesis documents the development, application, extension and modification of a model designed to estimate population-level frequencies of P. falciparum alleles and multi-SNP haplotypes and genotypes within a Bayesian framework. It is hoped that the model and its proposed framework will provide a practical tool for surveillance of antimalarial resistance, as well as a foundation on which to develop further methods.

Advisor: Holmes, C
Guerin, P
Flegg, J
Civil society knowledge networks

Information technology, media, financial flows and consumer culture have long been acknowledged as transnational connective forces that spread ideas and values around the globe. This work proposes an alternative mechanism for such spread: development-focused civil society organizations. This thesis argues that such organizations constitute a backbone of connections that link a diversity of development actors and local communities into a network with global scope. While individual nodes in these civil society networks may not possess global reach, the network as a whole facilitates the far flung transfer of knowledge and ideas. This work focuses on the ways that knowledge is generated, transferred and renegotiated on both the global, national and local scale through such networks of development institutions. How are global discourses formed, adapted and spread via civil society into local communities? How do local communities interact with, change, implement or ignore the values, knowledge and rhetoric of global movements? How are communities shaped by these discourses and what role do they have in informing the discourses themselves?
The project constructs two case studies of such 'knowledge networks' – two international foundations, their partner NGOs in the developing world (Kyrgyzstan and Kenya), and the local communities where the NGOs support ecologically-focused initiatives. The case studies demonstrate the complex and uneven ways in which knowledge and values are shared – and contested – within the networks. Ideas are transformed, adapted or ignored between different nodes, and yet the network retains enough common discourse and shared knowledge to function as a whole. Despite power imbalances, local actors remain agents, not subjects, in these networks and produce knowledge that is prized by other organizations and individuals in the networks. Civil society knowledge networks thus sculpt the content and application of knowledge across global movements, development-focused civil society organizations and local communities in the developing world.

Keywords: Kenya
East Africa
Participatory Development
Climate Change Adaptation
International Development
Borana
Kyrgyzstan
Envrionmental Knoweldge
Civil Society
Biocultural Diversity
Knowledge networks
Advisor: Beinart, W
Gooptu, N
And God created woman: an exploration of the meaning and the myth of Eve

The aim of my thesis is to destabilise the persistently pessimistic framing of Eve as a highly negative symbol of femininity within Western culture by engaging with marginal, and even heretical interpretations that focus on more positive or sympathetic aspects of her character. My objective is to question the myth that orthodox, popular readings represent the 'true' meaning of Genesis 2–4, and to explore the possibility that previously ignored or muted rewritings of Eve, which emphasise her knowledge or her motherhood, are in fact equally 'valid' interpretations of the biblical text.
By staging analytical and dialogic encounters between the biblical Eve and re-writings of her story, particularly those that help to challenge the interpretative status quo, my thesis re-frames the first woman using three key themes from her story: sin, knowledge, and life. Employing a method of ideological reception criticism, I consider how and why the image of Eve as a dangerous temptress has gained considerably more cultural currency than the equally viable pictures of her as a subversive wise woman or as a mourning mother.
To conclude, I argue that Eve is neither an entirely negative nor entirely positive figure, but rather that her characterisation, both biblically and in reception, is ambiguous and multivalent. My thesis thus offers a re-evaluation of the meanings and the myths of Eve, deconstructing the dominance of her cultural incarnation as a predominantly flawed female, and reconstructing a more nuanced and balanced presentation of the first woman’s role in the Bible and in her afterlives.

Advisor: Gillingham, S
Tombs and territories: the epigraphic culture of Lycia, c. 450 - 197 BC

In this thesis, I look at the use of inscriptions on stone in the Lycian peninsula during the fourth and third centuries BC, considering the effect of internal and external events on the production of inscriptions in the area, and looking at aspects of continuity and change across the two centuries.
In Chapter 1, I discuss the development of the Lycian alphabet, arguing that origins of the alphabet are far more complex than has usually been believed, and involved elements of both organic development and conscious devising of letters forms. Building on the work of earlier scholars, I consider the alteration of certain letters-forms over time, and use these – and other available indications of date - to allocated number of inscriptions from different sites to 'early' or 'later' periods; the results of this work are presented in the 'harts' at the back of my thesis.
In the subsequent chapters, I build on my conclusions from the first chapter to discuss certain aspects of the epigraphy of Lycia in a broadly chronological fashion, first setting out the what we know about the historical background of each period under discussion, and then considering inscriptions of particular interest.
In Chapter 2, dealing with the late-fifth and early-fourth century, I look at the earliest of the Lycian epitaphs, as well as the uniquely long inscriptions of the rulers of Xanthos. I consider the development and structure of the 'building formula' which is so common in Lycian inscriptions, and how this relates to other Anatolian epigraphy.
Chapter 3 looks at the effect of the internal strife in early-third century Lycia, and particularly the figure of Perikle, on the epigraphic culture of Lycia, with particular discussion of the ẽnẽ…χñtawata 'ruler formula', while Chapter 4 discusses the changes brought about by Hekatomnid rule over Lycia, and the beginnings of the use of Greek in private epigraphy.
Finally, Chapter 5 looks at the beginning of the Ptolemaic period, arguing that Lycian continued to be used in both official and private inscriptions, and discussing the ways in which official epigraphy became more similar to that of other Greek poleis – while retaining specifically Lycian features.

Keywords: ancient history
epigraphy
multilingualism
Lycian language
Greek language
Advisor: Crowther, C
Ma, J
Searches for scharms and gluinos with the ATLAS Detector

Following the extremely successful operation of the Large Hadron Collider at CERN during its first years of operation, the ATLAS and CMS collaborations announced the discovery of a new particle compatible with the Higgs boson in July 2012, finishing the complement of particles in the Standard Model. However, no other new particle was even hinted at, confounding predictions of an early discovery of Supersymmetry that would resolve the hierarchy problem and retain low fine-tuning. This thesis presents two searches for new phenomena that would have evaded early efforts. The first, using the full 8 TeV dataset collected in 2012 by ATLAS, targets heavy particles decaying to charm quarks and non-interacting particles through the use of a recently developed charm-jet identification algorithm. No excess is observed over the Standard Model predictions, so results are interpreted in the context of supersymmetric charm production. This is constrained to the highest masses so far, with scharms excluded at the 95% confidence level for masses up to 550 GeV with neutralino masses below 200 GeV. The second search makes use of the 13 TeV dataset collected in 2015, and looks for heavier particles which are produced with far higher cross section at this increased collision energy. It is sensitive to particles decaying via cascades to large numbers (≥ 7 to ≥ 10) of hadronic jets, with sensitivity enhanced through requirements on the number of jets identified as arising from bottom quarks. Again, no excess is observed, and so limits are set on gluino production in two cascade decay scenarios, with a significant increase in reach obtained over 2012 searches for the same final state – gluino masses below 1400 GeV are excluded in the models considered.

Keywords: Large Hadron Collider
Charm
Gluino
Multijet
13 TeV
proton - proton collisions
ATLAS
Supersymmetry
8 TeV
Advisor: Gwenlan, C
The end of the line: literature and party politics at the accession of Queen Anne

This thesis provides the first full-length account of the political and cultural significance of the accession of Queen Anne. It offers a critical reassessment of the politics of the royal image across a spectrum of texts, events, and artefacts—from panegyrics, newspapers, sermons, royal progresses, and processions to medals, coins, and playing cards. Recent scholarship has emphasized the importance of party politics to the literature and culture of the early eighteenth century. This thesis nuances that assumption by arguing: (1) that the principal focus of partisan texts was competing representations of monarchy; and (2) that the explosion of partisanship at the start of the eighteenth century was triggered by unrest about the royal succession.
Anne was the last protestant Stuart. She had no surviving children. This thesis explores how authors such as Daniel Defoe, Joseph Addison, Alexander Pope, and a great many lesser known and anonymous writers and propagandists conceptualized the end of the Stuart dynasty. Anne's accession forced writers to conjecture on the future succession. There were two rival claimants to the throne after Anne’s death: the protestant Electress Sophia of Hanover and Anne's Catholic half-brother, James Francis Edward. Sophia's claim was statutory, James's hereditary. Factions emerged in support of both claimants. Almost all topical writing took a stance on the issue. Many sided with the government, supporting Hanover. Yet some writers favoured the illegal but hereditary claim of James Francis Edward; they had to express support in covert ways. This succession crisis triggered not only printed polemic, but also swathes of clandestine manuscript literature circulating in the Jacobite underground. The government took a hard line on Jacobite writers and printers; this thesis documents both their persecution and the techniques they used to evade the law. The thesis concludes by suggesting that this oppositional literary culture only disintegrated after the defeat of the Jacobite rebellion, and the consequent settlement of the Hanoverian succession, in late 1716. After this point, royal succession ceased to be a major source of political discontent.

Advisor: Kewes, P
Womersley, D
The population structure of bacterial pathogens

Populations of many bacterial pathogens are structured into discrete strains despite frequent genetic exchange. Although insights from several studies suggest that different selection pressures operate in different areas of the genome, few theoretical and conceptual frameworks of bacterial population structure examine the effects of distinct competitive processes acting on different loci in the genome, and fewer still have considered the metabolic genes despite their increasingly-recognised importance in virulence. Buckee et al. (2008) investigated the combined effects of ecological competition operating at metabolic genes and immunological competition at antigenic genes on strain diversity using a stochastic model. A key prediction was that prevalent strains should show stable, non-overlapping associations between alleles of antigenic and metabolic genes. In this work, the roles of ecological and immunological competition in structuring bacterial pathogen populations is explored further using a multidisciplinary approach of mathematical modelling and whole genome analysis, focusing in particular on the well-characterised pathogens Neisseria meningitidis and Streptococcus pneumoniae as detailed case studies. We find support for the hypothesis that ecological and immunological competition play roles in structuring pathogen populations – even if present at relatively low levels – including support at the whole genome level. After extending the mathematical framework to encompass virulence-associated genes, we explore the effects of strain-targeted vaccination. We find that metabolic and virulence-associated genes from vaccine-strains are observed following vaccination in association with non-vaccine strains. The final chapter demonstrates how multilocus mathematical models coupled with whole genome analysis can be used together to gain additional insight into the evolution and population structure of bacterial pathogens.

Keywords: Metabolism
Bacterial strains
Bacterial population
Vaccination
Multilocus models
Advisor: Gupta, S
Maiden, M
The promise of zebrafish: a novel resource to study the myeloid response in vivo

Oncogenic transformation, local tissue damage at a site of injury, or invading pathogens all induce signals resulting in the recruitment of macrophages and neutrophils to the inciting stimulus. This study describes the development of an innovative binary approach in a zebrafish animal model that enables genome-wide profiling of specific cell types isolated directly from the in vivo context. The modular system harnesses the power of zebrafish genetics using an in vivo biotinylation system consisting of a zebrafish line ubiquitously expressing a nuclear envelope with an Avi-tag. The Avi-tag is biotinylated by the biotin ligase, BirA, specifically expressed by macrophages and neutrophils, and subsequently the nuclei of these cells types can be isolated by streptavidin affinity purification. The model was used to profile the active transcriptome of neutrophils in two disease pathologies, Mycobacterium marinum infection and the earliest stages of melanoma. For studies of the immune response to M. marinum infection, a granuloma-forming model was optimised, which recapitulates human tuberculosis. Profiling revealed a unique transcriptional signature for neutrophils, characterised by both factors that are host protective and those that may contribute to the pathogenesis of the disease. For studies of melanoma onset, we have generated a novel inducible model for melanocyte oncogenic transformation. The model for melanoma onset was crossed to the binary neutrophil-specific in vivo biotinylation model. Profiling of the neutrophils in response to oncogene-transformed melanocytes revealed a neutrophil transcriptional signature consistent with a pleiotropic role for neutrophils at the onset of melanoma. Not only does the model generated in this study prove to be an excellent resource for studying inflammation in vivo, but the data obtained provides novels insights into the role of neutrophils in mycobacterium infection and the onset of melanoma, that can be extended to human studies and harnessed for immunotherapy.

Advisor: Sauka-Spengler, T
Cerundolo, V
Psychiatric compulsion and long-term social outcomes for patients with psychosis: is there an association?

Compulsory interventions are widely used in general adult psychiatry for the treatment and care of patients with severe mental illness. While involuntary hospitalisation is established in practice around the world, the use of compulsory interventions outside of hospital – so called community treatment orders (CTOs) – is a more recent development. Three randomised controlled trials of CTO effectiveness have been conducted to date finding no benefits for patients in terms of reduced relapse and readmission to hospital. However, these trials have been relatively short (11-12 months) and focused almost exclusively on CTO effects on clinical functioning and service use. Little attention has been given to patients' social outcomes and broader welfare despite their recognised importance. A sub-sample (n = 121) from the Oxford Community Treatment Order Evaluation Trial (OCTET) were interviewed 48-months after randomisation to assess whether the duration of the CTO intervention was associated with more or less favourable social outcomes at follow-up. Social outcomes were assessed using three main concepts: social networks (Study 1), social inclusion (Study 2), and capabilities (Study 3). No significant associations between the duration of the CTO intervention and social outcomes at follow-up were found. The association between involuntary hospitalisation and social outcomes was also tested but no significant associations were found. Because the field of social outcome measurement is relatively undeveloped, a further aim was to contribute to the validation and testing of two recently developed instruments: the Social and Community Opportunities Profile (SCOPE) (Study 4) and the Oxford Capability Questionnaire for Mental Health (OxCAP-MH) (Study 5). The SCOPE performed well overall as a measure of social inclusion but questions were raised about its feasibility (length) and the reliability of one of its sub-scales. The OxCAP-MH demonstrated good psychometric properties (reliability and validity) and represents a promising new multi-dimensional patient-reported outcome measure for use in mental health research.

Keywords: Social outcomes, outcome assessment, psychosis, psychotic illness, community treatment orders, CTO, out patient commitment, coercion, compulsory treatment, involuntary treatment, involuntary detention, forced treatment, social networks, social inclusion, social and community opportunities profile (SCOPE), capabilities, capability approach, OxCAP-MH, follow up, RCT, longitudinal,
Advisor: Rugkasa, J
Simon, J
Burns, T
Compulsivity in anorexia nervosa

Anorexia Nervosa (AN) is a psychiatric disorder characterised by persistent self-starvation, which has high mortality rates, and low rates of recovery. In conjunction with a lack of effective treatments, the serious nature of the disorder emphasises the need for research investigating the underlying processes contributing the persistence of the disorder, and the identification of novel avenues for treatment development.
In individuals with AN, dietary restriction often takes on a driven and compulsive quality, with increasing suggestion of parallels with other disorders featuring compulsive behaviour, such as Obsessive-Compulsive Disorder (OCD) and substance dependence. The commonalities and comorbidities in compulsive behaviours across a range of disorders have been highlighted by Robbins et al (2012), who propose a transdiagnostic approach to compulsivity, arguing that this behavioural construct has cross-diagnostic significance. Conceptualising compulsivity in this way may aid in the development of novel research avenues investigating the learning processes and neurobiological mechanisms underpinning this behaviour. In light of this, the aim of this thesis was to investigate the compulsive nature of behaviour in AN, and the behavioural and neural underpinnings of this behaviour guided by research carried out in other compulsive disorders.
Chapter 1 reviews models of the neural and behavioural underpinnings of compulsive behaviour, and discusses these in relation to compulsive behaviour in AN. Chapter 2 presents qualitative data supporting parallels between the subjective experience of compulsive behaviour in AN and substance use disorders (SUDs). These parallels are further examined in Chapter 3, in which two novel measures of compulsive weight-loss behaviour were developed and validated by adapting a questionnaire assessing addictive behaviour. Chapter 4 presents data suggesting that these parallels in behaviour do not reflect a common tendency to develop habits in learning, as found in substance dependence and OCD. The electrophysiological data presented in Chapter 5 was unable to provide evidence that AN may be underpinned by dysfunction of the neurocircuitry seen in other compulsive disorders. Whilst these studies support suggestion of parallels with substance dependence, at least at the level of self-report, the hypothesised parallels in the underlying behavioural and neural mechanisms were not found.

Advisor: Park, R
Harmer, C