VictorJuiz/thesis huggingface dataset:
Predicting inhaled steroid responsiveness using blood eosinophil counts: personalising long-term management of COPD in primary care

Background
Management of chronic obstructive pulmonary disease (COPD), including initiation of inhaled corticosteroids (ICS), has thus far generally been based on a ‘one-size-fits-all’ approach. However, benefits of ICS are unclear, and they may harm some patients. Blood eosinophils have been identified as a readily available biomarker to guide decisions about ICS treatment in COPD, but they have not been studied in an ICS-naïve, primary care population. A device for estimating blood eosinophil counts at the point of care is now available. This doctoral project aimed to characterise blood eosinophils and ICS responsiveness in people with COPD in primary care, as well as assess agreement between near-patient vs. laboratory testing for blood eosinophils.
Methods
This project comprises two major studies, each with several constituent parts. First, a study of 30,378 routinely-collected primary care records were used for descriptive and hypothesis-testing components. Second, a prospective cohort study recruited 96 participants to obtain laboratory and near-patient blood eosinophil data at multiple visits over a six-month period.
Results
Approximately half of patients fell into a ‘medium’ category of eosinophils in the range 0.15 to 0.34 x10*9/L. Repeatability of eosinophil counts was either ‘good’ or ‘excellent’ in the two cohorts. There was a lower risk of acute exacerbations in patients with higher eosinophil counts who were prescribed an ICS, with a clear ‘dose-response’ by eosinophil count. There was no clinically important difference between near-patient and laboratory eosinophil values.
Conclusions
Patients with higher blood eosinophils are more likely to benefit from ICS. Blood eosinophil counts are generally repeatable and are applicable for guiding ICS treatment decisions in primary care. Blood eosinophil categories in combination with other clinical features such as acute exacerbation frequency could provide a more personalised approach to pharmacological management of COPD. Near-patient eosinophil count testing could support rapid decisions about ICS treatment in primary care.

Keywords: Pharmacoepidemiology
Inhaled corticosteroids
Blood eosinophils
Primary care
Chronic obstructive pulmonary disease
Point-of-care testing
Advisor: Butler, Christopher
Bafadhel, M
McFadden, E
Smith, M
A pipeline for high precision partial differential equation computation

In this thesis, we investigate the application of the cubature on Wiener space method(also known as the Kusuoka-Lyons-Victoir algorithm) to solving parabolic type lin-ear partial differential equation problems. The framework for the cubature methodwas first developed in the seminal paper [Lyons and Victoir, 2004]. Since then,several key ideas have been introduced to improve the method’s computationaltractability, hence practicality, without affecting its approximation order. We re-view these ideas in chapter 1.
Building on those works, in this thesis, we investigate the use of nonlinear adaptiveapproximation in the cubature framework, to further extend cubature’s practicalapplicability. In particular, we utilise adaptive approximation as an additional com-putation pruning device, so that existing techniques could be successfully applied tocertain Cauchy problems that do not have a predetermined boundary. Example ofsuch problems include compound options and certain path dependent options fromfinance. Using our ideas, we demonstrate using non-trivial numerical test examples(see chapter 3), that we were able to achieve more than two orders of magnitudereduction in overall computation – shortening the “naive” approach, which wouldhave required weeks/months, to minutes on consumer hardware – without affectingthe order of approximation. The amalgamation of cubature and adaptive approx-imation relies on our carefully designed partitioning and memoisation algorithms.Naive treatment of such is well known to suffer from the curse of dimensionality.We explain these ideas in chapter 2.
In summary, this thesis demonstrates the pipeline of carefully designed techniquesthat are necessary for the successful application of the high order cubature onWiener space method to practical problems.

Keywords: high order weak approximation of stochastic differential equations
Advisor: Lyons, T
Babbar, K
Bayesian inference and machine learning methods for the advanced analysis of electrocardiographic signals

The realisation of precision cardiology requires novel techniques for the non-invasive characterisation of individual patients’ cardiac function to inform therapeutic and diagnostic decision-making. Both electrocardiography and imaging are used for the clinical diagnosis of cardiac disease. The integration of multimodal datasets through advanced computational methods could enable the development of the cardiac ‘digital twin’. A cardiac digital twin is a comprehensive virtual tool that mechanistically reveals a patient’s heart condition from clinical data and simulates treatment outcomes. The adoption of cardiac digital twins requires the non-invasive efficient personalisation of the electrophysiological properties in cardiac models.
This thesis presents novel computational techniques to exploit the synergy between Artificial Intelligence and multimodal datasets towards efficiently producing cardiac digital twins from non-invasive routinely acquired clinical data modalities, namely, ECG and cardiac magnetic resonance (CMR) imaging. I present and evaluate
-> an efficient Bayesian-based inference method for estimating the ventricular activation properties from electrocardiographic data through CMR-based modelling and simulation,
-> and a machine learning-based ECG delineation methodology capable of generalising to new databases to enable the translation of my inference method into real-world clinical applications.
These two methodologies, combined with CMR-based cardiac anatomical reconstruction, compose the foundations for an end-to-end cardiac digital twin generation pipeline from non-invasive standard clinical data modalities.

Keywords: Deep learning
Modelling and simulation
Eikonal
Bayesian inference
Cardiac research
Earliest activation sites
Electrocardiogram
Magnetic resonance imaging
Conduction speeds
Machine learning
Cardiac digital twin
Advisor: Rodriguez, B
Minchole, A
Using bacterial DNA sequencing data to investigate the epidemiology of plasmid-mediated antibiotic resistance

Bacterial plasmids are extra-chromosomal genetic elements, which can act as efficient vectors of antibiotic resistance. Epidemiological insight into plasmids may be gained by applying plasmid typing schemes, which exploit loci involved in replication and mobility functions (replicon and MOB typing, respectively). In Chapter 2, I compiled a curated dataset of complete NCBI plasmids to assess the performance of in silico replicon and MOB typing in terms of concordance and ‘typeability’ (proportion of plasmids typed). I found a degree of non-concordance between the schemes, which was attributed to either ambiguous boundaries between MOBP/MOBQ types, or the mosaic nature of some plasmid genomes. Ultimately, I showed that the schemes fail to accommodate the diversity of plasmid genomes; of ~14000 curated bacterial plasmids, only 42% and 55% could be assigned a replicon and MOB type, respectively. Given the limitations of plasmid typing, I subsequently focused on whole genome sequencing (WGS) analysis approaches capitalising on the wider plasmid genome. High-throughput DNA sequencing has produced 1000s of bacterial WGS datasets. However, such datasets commonly comprise short sequencing reads, which yield fragmented assemblies; this makes comparative analysis of plasmid genomes challenging. In Chapter 3, I developed two methods for comparative plasmid analysis, which cluster short-read sequenced samples according to 1) plasmid replicon types; 2) sample-vs-reference plasmid distance score profiles. However, benchmarking suggested neither method is completely reliable. The rise of long-read sequencing technology has increased the availability of complete plasmid assemblies, facilitating comparative plasmid genomic analyses. Nevertheless, available alignment-based comparative genomic tools have limitations: they often do not provide metrics on structural similarity and lack flexibility in terms of input/output options. Therefore, in Chapter 4, I developed a novel alignment-based tool (‘ATCG’) for calculating pairwise average nucleotide identity (ANI), coverage breadth, and structural similarity, while addressing limitations of existing alignment-based tools. Benchmarking demonstrated favourable runtimes and supported the validity of calculated ANI scores. In Chapter 5, besides curating an updated plasmid dataset, I curated sample metadata (e.g. isolation source, geography). Using this metadata and plasmid biological features, I conducted multivariate statistical analyses to determine factors associated with plasmid resistance gene carriage, analysed across major resistance gene classes. The analysis yielded interesting findings, for example, demonstrating that patterns of plasmid antibiotic resistance carriage in livestock and humans reflect known antibiotic usage.

Keywords: genomic epidemiology
computational biology
statistical modelling
comparative genomics
One Health
plasmids
data curation
antibiotic resistance
whole genome sequencing
Advisor: Walker, A
Sheppard, A
Anjum, M
Phan, H
Doumith, M
Karl Philipp Moritz’ Anglophilie: Kultur- und Literaturvermittlung im späten 18. Jahrhundert

This dissertation examines Karl Philipp Moritz’s Anglophilia: its nature, how it enriches his own works, and to what extent he can be seen as a cultural mediator. Traces of Anglophilia can be found throughout Moritz’s oeuvre. Examples include his travel book Reisen eines Deutschen in England, his published but so far under-researched translations of four English novels and three non-fictional writings, and the many references to English authors and their works within his own such as Anton Reiser, which all clearly indicate his love for England. The findings of this dissertation show that Moritz’s Anglophilia is closely related to his interest in human nature and behaviour, and is characterised by personal discovery and intellectual necessity. It is a constant in his life and exerts an all-encompassing influence on his thinking and writing, blending in with his oeuvre as a whole as well as complementing it. Moritz’s social and literary environments, as well as his travels through England, provided him with the knowledge and means for his Anglophile reflections and his mediation of novel perspectives on English culture and literature. However, his Anglophilia is not only an element of his environment, but serves as an active instrument. He uses his published translations of English works to reflect on the existing social system, to explain various norms of behaviour and cultural peculiarities, and to present overarching ideals and politically progressive thoughts while encouraging the readership towards moral and utopian contemplation. In addition, he adapts English works he admires for autobiographical self-analysis and self-criticism and to discuss human nature. Shakespeare’s dramatic works serve Moritz in the expression of the psychological development of his persona Anton Reiser by staging his own life realities when facing existential liminal experiences. Milton’s Paradise Lost helps Moritz to intensify and process his feelings, to again articulate his existential problems but also conceptualise solutions, and to discuss and formulate moral-philosophical and metaphysical positions.

Keywords: travel writing
cultural mediation
Anglophilia
18th century translation
reception of English literature
literary mediation
Advisor: Robertson, R
Ancient DNA perspectives on pathogen evolution in domestic animals

Pathogens, animals (domesticated or not) and humans have intertwined evolutionary trajectories for millennia now, with this relationship intensifying after the Neolithic Demographic Transition and its subsequent epidemiological transition that increased the exposure of animal populations to pathogenic reservoirs. Incorporating the temporal dimension in the study of disease evolution requires the incorporation of ancient pathogen DNA data in phylogenetic and population genetic analyses, which is not a simple task. Limited DNA survival and DNA damage, however, have hindered the search for ancient pathogens. For these reasons the accurate identification of microbial species from archaeological samples is integral and has the potential to provide an unprecedented perspective on the evolutionary history of major diseases that have affected humans and domestic animals. In the first chapter of this thesis I propose a novel analytical method for metagenomic identifications, HAYSTAC, which can also be applied for direct hypothesis testing regarding the presence of pathogens in metagenomic samples. By employing a clear probabilistic model for species identification from shotgun sequencing DNA data, along with incorporating additional algorithmic steps for taxonomic result validation, robust metagenomic identifications from sequencing data generated from archaeological samples become possible, with a significantly lower false positive rate when compared to pre-existing and established methods. In the second chapter of this thesis I used HAYSTAC to screen more than one thousand archaeological and modern chicken samples for Marek’s Disease Virus (MDV), a devastatingly virulent virus threatening the modern poultry industry. Following the DNA sequencing of archaeological chicken samples positive for MDV, I reconstructed the genomes of these ancient strains and compared them to modern ones. Through a time dependent phylogenetic reconstruction approach, I identified the possibility that modern MDV strains are evolving at an accelerated rate compared to ancient ones, with modern highly virulent strains possibly evolving from a potentially non-virulent (ancient) form (prior to 1907) of MDV, a finding that can have a significant impact on improving the health status of domestic chicken population globally. In the third chapter of this thesis, I examine if the process of domestication has had an impact on the disease burden of domestic pigs and dogs, by applying HAYSTAC. By applying hypothesis-driven species identification methods, I focused on screening animal derived metagenomes for zoonotic bacterial pathogens. Since many of the causative agents of these zoonotic diseases became prevalent in a post-industrial context, the results of this approach will be able to offer insights into how human activity has reshaped the landscapes of both the natural environment and animal diseases.

Keywords: zoonotic pathogens
pathogen evolution
metagenomics
ancient DNA
Advisor: Larson, G
Cityzenship: a study of transnational Chinese student returnees in three megacities in mainland China

This thesis is a qualitative study of the return migration of overseas Chinese students. When overseas students return to China, many do not return to their hometown but usually land, work and settle down in one of China’s megacities: Beijing, Shanghai and Shenzhen. Their return migration is thus not only transnational migration but also internal-urban migration.
To study the migration of transnational Chinese student returnees to megacities, I conducted a one-year multisited ethnographic research in China. I stayed in three cities: Beijing, Shenzhen and Shanghai, from September 2018 to August 2019. Data were collected by semi-structured interviews with 90 returnees (30 participants in each megacity) graduating from universities in the United Kingdom, United States, Korea, Australia, Germany, France and Hong Kong. I also observed and lived with participants, took photographs and field notes.
This study proposes a framework I call cityzenship to bridge scholarship on transnational return migration and internal-urban migration. This thesis explains cityzenship as membership attached to multiscalar communities, as embodied and practiced identities and as class-based rights. Moreover, this thesis illustrates how cityzenship reproduces domestic social and geographical inequalities. It also proposes the importance of the lens of family in the analysis of practices of cityzenship.

Advisor: Waters, J
Microstructure imaging with diffusion MRI and microscopy

Diffusion MRI is a powerful, non-invasive tool for microstructure imaging because of its sensitivity to structures on the microscopic scale. By analysing the diffusion signal we can infer the structural connectivity of the human brain or changes in the myelo- and cyto-architecture. This inference requires biophysical signal modelling, where we aim to map macroscopic diffusion signals onto biologically-meaningful tissue parameters. However, this mapping is often ill-posed, with multiple parameter sets fitting the signal equally well, and our parameters are said to be degenerate. Because degenerate parameters lack tissue specificity and are thus difficult to interpret, they present a serious challenge to diffusion modelling and limit the widespread application of diffusion MRI in both neuroscience research and clinical medicine.
This thesis explores various ways in which we can overcome parameter degeneracies to enable more specific microstructural interpretation of the diffusion signal. Consequently, this work spans species (human and macaque), tissue states (in vivo and postmortem), modalities (MRI and microscopy) and signals over four orders of magnitude, from sub-micron microscopy images to MRI at the millimetre scale. In particular, we develop two biophysical models of the white matter that aim to separate the diffusion characteristics from the tissue architecture (i.e. the fibre orientation, dispersion and density) and present a truly unique, multimodal dataset: the BigMac dataset. This dataset combines extensive MRI data with multi-contrast microscopy to characterise a single macaque brain in exquisite detail and will establish an innovative data platform from which we can interconnect microstructural features with MRI signals throughout the brain.
Overall, the models and data presented in this thesis aim to further our understanding of how microscopic tissue features influence the observed diffusion signal. We hope that this work will enhance the biophysical interpretation of diffusion MRI and ultimately advance in vivo quantification of the brain tissue microstructure.

Keywords: diffusion modelling
polarised light imaging
microstructure Imaging
brain imaging
microscopy
diffusion MRI
white matter
data fusion
histology
Advisor: Miller, K
Jbabdi, S
The literary form of the Middle English pastoral manual with particular reference to the Speculum Christiani and some related texts

Pastoral manuals are designed as practical aids to the proper execution of the cura animarum and address themselves to the most immediate problems of parish life: basic catechesis of the laity and the administration of the Sacraments. By looking at the provision made in such works for teaching the rudiments of the Christian faith, it is possible to see how such books developed and evolved to meet the changing needs of the parish clergy (and ultimately of the literate layman), and to see the place of one of the most popular of such works, the Speculum Christiani, in this tradition of pastoral aid.
The first section, â€˜Contextâ€™, opens with an analysis of the legislation issued by the bishops in the thirteenth and fourteenth centuries, and shows how it influenced and encouraged the emergence of manuals of pastoral care which were distinct from the larger penitential reference books. It examines the developing concern with ignorantia sacerdotum and discusses the ways in which the syllabus of instruction included in many sets of constitutions became a structural norm for the contents of the pastoral manual. Chapter two examines the elementary and grammar schools and their books to show the ways in which pastoral handbooks were perhaps influenced by and overlapped with the 'set-texts' in the medieval English schools. Chapter three is a study of some of the Latin and vernacular pastoral manuals found in clerical miscellanies from early in the thirteenth century to early in the sixteenth. It examines the form of these manuals, how their contents changes and how their authors developed techniques for presenting and enlivening basic teachings. The influence of the pastoral tradition on works such as Piers Plowman is also considered.
Section two, â€˜The Evolution of the Speculum Christianiâ€™, is in the nature of a case history. In chapter four 1 discuss the Latin summa called Cibus Anime which seems to have provided most of the Latin quotations which make up the Speculum. An account of the versions of the text is given and the character of the text is discussed. An attempt is made to suggest the provenance and date of the work, which is anonymous. Chapter five provides a detailed analysis of the Speculum Christiani showing how its compiler exploited the resources of the Cibus Anime, reorganising the material into a working handbook of the pastoral care. A series of analytical tables chart the dependence of the Speculum upon the Cibus Anime and analyse the contents of some anomalous copies. The circulation of additional Latin texts (not included in the EETS edition of the Speculum but often found in the manuscripts) is charted and transcriptions of the texts provided. Some other works which also appear to draw on the Cibus Anime to support vernacular and Latin texts are discussed.

Keywords: literary form
Middle English
doctrines
pastoral theology
pastoral manual
clergy
Christian literature
Speculum Christiani
Social evolution in viruses

Viruses are the most diverse and abundant lifeforms on Earth. In this thesis, I argue that they are also social organisms, and that it can be useful to study viruses within the framework of social evolution theory. Specifically, I: (i) define how cooperating and cheating can occur in viruses, review the diversity of viral cheats, and suggest why studying them can be useful for both virology and evolutionary biology; (ii) model how beneficial interactions between different viral variants can increase the genetic diversity of viral infections; (iii) model how beneficial interactions between viruses can promote the evolution of group dispersal in viruses; (iv) model distinct reasons for why vertically transmitted symbionts, viral or otherwise, are more cooperative than horizontally transmitted ones; (v) investigate the abundance of defective interfering ‘cheat’ genomes in natural infections of Influenza and SARS- CoV-2. Overall, I suggest that the nascent field of sociovirology has much to offer virologists and evolutionary biologists alike.

Keywords: Virology
Conflict
Cooperation
Altruism
Social evolution
Adaptation
Viruses
Evolutionary Biology
Sociovirology
Advisor: West, S