VictorJuiz/thesis huggingface dataset:
Measuring the impact of reduced antibiotic use in hospital settings using electronic health records
Keywords: antimicrobial stewardship
antibiotics
electronic health records
mortality
cluster-randomised controlled trial
secondary care

Hospital inpatient antibiotic use has increased year-on-year in the NHS despite considerable investments in stewardship activity. Although hospitals have financial incentives to reduce overuse, current antibiotic reduction targets are modest and hospital stewardship leads have expressed significant concerns about the safety of achieving antimicrobial reduction targets, due to fears of under-treatment leading to patient harm. To reassure practitioners and the public that substantial reductions in antibiotic use could be safe, this thesis begins by exploring associations between variation in hospital-level antibiotic prescribing and patient-level clinical outcomes in 36 million general medicine admissions in England. I use this analysis to estimate what system-wide reductions might, at least in theory, be safely achieved if higher-using hospitals could replicate the prescribing practices of low-using hospitals. I then use patient-level antibiotic and outcome data to investigate the causal effect of using shorter versus longer antibiotic courses by treating time-varying antibiotic use as sequence of non-randomised nested “trials”. Although observational analyses cannot prove shorter antibiotic courses are safe due to the potential for residual confounding, finding no evidence of harm can help to justify the evaluation of antibiotic reduction strategies in randomised experiments for unbiased inference. To inform its adoption in other acute care settings, the thesis then addresses two key questions emerging from the recently completed ARK-Hospital cluster-randomised trial, which tested a multifaceted behaviour change intervention to reduce antibiotic overuse in general medicine. Since the intervention effect varied widely by site, I examined the role of 26 contextual factors as potential mediators of impact, to better understand sources of this between-site variation. Finally, although the intervention had a modest impact on antibiotic prescribing trends overall, trends in non-ARK sites are unknown, and I therefore compared ward-level prescribing trends in ARK vs non-ARK sites to understand whether the intervention had a greater (or lesser) impact than suggested by the trial-site specific analysis alone. The thesis discusses the analytic challenges of using routine electronic databases to compare antibiotic treatment durations and evaluate antimicrobial stewardship initiatives, and highlights the implications of specific data quality and accessibility issues for investigators and policy makers. Overall, the thesis demonstrates the need for high-quality health-record-linked e-prescribing systems to support robust assessments of the impact of antibiotic reduction strategies.
Applications of stochastic analysis and algebra to machine
learning
Keywords: Signature cumulants
Kernel learning
Adapted topologies
Entropy
Stochastic analysis
Scoring rules
Kernelized cumulants
Signatures

In this thesis we consider the application of tools from stochastic analysis and algebra to statistics and machine learning. Most of these tools are different forms of what has become known as signature methods. The signature has been discovered and rediscovered in a few different areas of mathematics in the last 70 years. In short, it maps a path evolving in a vector space to a group enveloping that same space. The reason it is so useful for statistics is twofold: One, its set of invariances is highly desirable in many applications, and two, its image group is highly structured making it particularly amenable to mathematical study using algebraic tools.
The primary aim here is to study how one may use the signature to express statistical properties of a given path, and how these properties can be applied to machine learning. This aim manifests itself as - among other things:
- a new type of cumulants for signatures that have unique combinatorial properties and can be used to characterise independence of paths,
- cumulants on reproducing kernel Hilbert spaces which are related to the signature cumulants, even though signatures are not used explicitly,
- a generalisation of the signature to other types of feature maps into non-commutative algebras,
- a feature map with an initial topology that captures properties of the filtration of stochastic processes,
- and a family of scoring rules with associated divergences, entropies and mutual informations for paths that respect their group structure.
These are divided into separate, self contained chapters that can be read independently of one another.
A tale of two civitates: on the origins and meaning of the concept of subsidiarity
Keywords: political theology
patristics
Jewish-Christian
subsidiarity

This work traces back the origins of the principle of subsidiarity to second Temple Judaism and the constitution, based on spiritual authority, of an autonomous intermediary sphere between political authority and individuals. It argues that the foundational premise of the subsidiarity tradition derives from ancient Jewish sources, and not from Aristotelian thought or the ancient Greek social reality. Then it argues that Jewish intermediacy is the basis of Christian intermediacy, characterized by universalism and the belief on the already here presence of the kingdom of God, as developed by Jesus of Nazareth and Paul of Tarsus. Christian intermediacy, in turn, is presented as the basis for the Christian political ambivalence that characterizes patristic political thought, which considers the Roman Empire as both a providential instrument of God and a new Babylon. This ambivalent perspective was inclined towards a providential vision of the Empire because of the conversion of Constantine, who inaugurated subsidiarity by combining the “negative” obligations of intermediacy with the “positive” obligations of a Christian Emperor to help the Church. Nonetheless, Constantinian subsidiarity evolved over the life of the Emperor into an overreaching and controlling doctrine of divine kingship, which was afterwards resisted politically and theologically by figures like Athanasius of Alexandria, Hilary of Poitiers, Ambrose of Milan, and Augustine of Hippo. This process culminated in a dispute about the proper form of subsidiarity and in a theoretical detachment of Church and Empire. Augustine of Hippo transformed subsidiarity into a general ethical principle, independent of the contingent relationship between the Roman Empire and the Christian Church. He also philosophically reinstalled ambivalence at the centre of Christian political theory and denied any special role for Rome and its emperors in the divine economy of salvation. Thomas Aquinas’ concept of subsidiarity, which has been frequently presented as the first formulation of the principle, is in fact strongly attached to Augustine’s one. His innovation consisted in systematizing the principle as a principle of justice, starting from Augustine’s ethical formulation of it. The thesis ends by arguing that this original conception of subsidiarity attached to Christian ontology is in tension, but not necessarily in contradiction, with the modern secular order, and that the present ambiguity of the principle can be explained by that tension.
#AfricaToTheWorld: Economic emancipation and identity affirmation in the age of global digital media
Keywords: Nigerian popular culture
afrobeats
globalization from the South
Lagos
digital capitalism
African youth
global media

The thesis explores a particular historical moment: the integration of Nigerian music into the global flows of popular culture, popularly referred to as the “Africa to the world” movement by professionals and fans alike. The research is based mainly on ethnographic data from what is commonly referred to as the “Nigerian music industry,” a fluid network of structures and mobile agents organized around hubs all along the Nigerian ethnoscape, with Lagos its key nod. Data collection involved a year of physical ethnography in Lagos, several months of participant-observation and interviews in Istanbul, London, Dubai, and Paris, as well as four years of digital ethnography.
Through the individuated mode of cosmopolitan success that Nigerian artists embody, the thesis explores the articulation of mobility, identity, and future-making in the age of global digital media. In particular, it takes seriously the popular hopes associated with the symbolic inclusion of “Africa” in the transnational commercial landscape in order to interrogate how imaginative, discursive, and affective practices interact with political economic processes. As masses of youths across the continent and diaspora root for music professionals who work tirelessly to hijack the structures of global capitalism and become “billionaires,” the thesis questions the empirical relevance and analytical power of seemingly entrenched and stable power dynamics inscribed in conceptualizations such as global/peripheral or capitalist/informal. It aims to move beyond categories that have limited emic resonance in order to analyze emancipatory world-making projects deployed by a postcolonial and post-privatization generation that appears to have internalized the flexible condition.
Identification and functional validation of pathogenic small nucleotide variants in patients with craniosynostosis
Keywords: genes
clinical genetics
craniosynostosis

Craniosynostosis, the premature fusion of the cranial sutures, affects ~1 in 2,000 live births. It is a heterogenous disorder with documented monogenic, polygenic, chromosomal, and environmental causes. Although many patients with a genetically determined cause harbour a variant in one of just seven genes, or have a chromosomal abnormality, there is a long tail of rarer genetic diagnoses with over 60 genes known to be recurrently mutated. Despite the recent uplift in knowledge of the genetic causes of craniosynostosis and the biogenesis of the cranial suture, there remains a suspected 10% of undiagnosed patients with a putatively pathogenic monogenic cause. In my analyses I aimed to target this subset of patients to delineate novel genetic causes of craniosynostosis. Using data generated from genome and exome sequencing I developed systematic pipelines to screen for small nucleotide variants. This approach identified 8 variants that explained the phenotype of previously undiagnosed patients (n = 114) enrolled in the UK 100,000 Genomes Project (100kGP) and highlighted additional candidate genes for further scrutiny. The candidate genes were included alongside 35 additional genes with reasonable evidence for involvement in craniosynostosis in a panel-based resequencing analysis of 617 individuals without a genetic diagnosis. Through this approach, I identified 8 diagnostic variants and 15 additional candidate variants. Drawing on the identification of pathogenic variants from the UK 100kGP, my resequencing analysis, and genes identified through other sources, I undertook experiments to explore and functionally validate the likely pathophysiological mechanisms associated with variants in three genes (PRRX1, PTCH1, and SPRY1) by using immunofluorescence, mouse models, and RNA and protein assays. Overall, this work has achieved improved diagnostic pipelines for craniosynostosis, and rare disease more widely, and has also served to delineate three new genetic causes of craniosynostosis by providing a key evidence base to support variant pathogenicity.
Identification of epigenetic regulators of RNA editing mechanisms
Keywords: bromodomain
pharmacology
genetic
ADAR
neurogenetics

This thesis looks to identify up-regulating mechanisms of ADAR 2 (Adenosine deaminases acting on RNA 2) through investigation of 52 novel small-inhibitor small molecules provided by the Structural Genomics Consortium (SGC, 2022). These small molecules were incubated with neuronal-2A mouse cells containing a CRISPR engineered construct, this doxycycline-induced construct was formed of a stem loop with a point mutation with mCherry and eGFP proteins respectively either side of the stem loop. The point mutation meant that the stem loop, along with the eGFP, was not translated, therefore levels of RNA repair could be measured by quantifying the ratio of eGFP/mCherry fluorescence. Upon identification of five significant up-regulators of RNA editing activity, and eight significant down-regulators, we repeated the treatment but this time extracted RNA and performed a qPCR which revealed that these identified treatments significantly effected either the expression of ADAR1, ADAR2 or both. It was interesting to note that bromodomain inhibitors appeared to have the greatest transcriptional effect upon ADARs. Next we used siRNA to knock-out ADAR 1 and ADAR 2, then repeating the fluorescence experiment. It is interesting to see that whilst ADAR 1 was seen to be up-regulated, inhibition of ADAR 1 did not inhibit transcriptional effects of treatment. On the other hand, inhibition of ADAR 2 led to decrease in efficacy of small molecule treatment. This thesis goes on to present the results of bromodomain 7 inhibition and it's effect upon ADAR, arguing that bromodomains are a key regulator of ADAR activity, as well as identifying potential targets in the treatment of neurogenetic diseases.
Hong Kong EFL pre-service teachers’ readiness for technology integration into future teaching practices: An explanatory sequential mixed methods study
Keywords: TPACK
self-efficacy
technology integration readiness
EFL pre-service teachers

The significance of integrating Information and Communication Technology (ICT) into Englishas a Foreign Language (EFL) education is widely recognised in modern EFL teaching practices. Teachers are expected to demonstrate professional expertise and proficiency in digital skills fromtheoutset of their teaching careers. This requirement has become particularly prominent in the aftermathof the outbreak of the COVID-19 pandemic, which forced a shift from physical classrooms to onlineplatforms. However, there has been limited research examining whether EFL pre-service teachers areready for technology integration before they enter actual classrooms.
Using an explanatory mixed methods research design, this study investigates the readiness for technology integration of EFL pre-service teachers from two universities in Hong Kong by exploringtheir knowledge, self-efficacy, and prior experience in technology integration. An online questionnaire is designed to examine their Technological Pedagogical Content Knowledge (TPACK) and self-efficacy for integrating technology into EFL teaching. Follow-up interviews are conductedtounderstand participants’ self-reported survey results and factors that influence their readiness levels.
The synthesis of quantitative and qualitative findings reveals that pre-service teachers’ readinessfor technology integration is influenced by a blend of experiential and contextual factors, with their technological experiences during teaching practicums playing a prominent role. While the majorityof EFL pre-service teachers exhibit a moderate level of preparedness, the considerable disparities inreadiness, particularly between the highest and lowest scores, underscore the necessity of teachertraining programmes to enhance their readiness for technology integration in their future classrooms. These findings hold theoretical significance as they offer a holistic perspective, combining knowledge-based and self-efficacy-based insights, into the factors influencing the varying levels of pre-service teachers’ technology integration readiness. Additionally, this dissertation offers practical suggestions for teacher-training programmes. These include diversifying ICT courses for pre-serviceteachers, furnishing comprehensive professional training to both teacher educators and pre-serviceteachers on integrating content, pedagogy, and technology effectively, and fostering pre-service teachers’ ability to address technical issues and meet the varied needs of their students. Moreover, considering participants’ eagerness for continuous professional growth, this study contends that teacher-training programmes should facilitate communication and collaboration among pre-serviceteachers across universities and afford them opportunities to attend cutting-edge technology exhibitions, thereby immersing them in innovative teaching practices.
Applying quantitative image analysis to liver cancer
Keywords: liver
cancer
magnetic resonance imaging

Survival rates are poor for hepatocellular Carcinoma (HCC) compared to many other cancers, and death rates are increasing in countries such as the United States and United Kingdom. To improve outcomes, tumours need to be detected at a much earlier stage. Magnetic resonance imaging (MRI) may provide a method to detect tumours earlier, potentially combined with other biomarkers.
The hypothesis underlying this thesis is that the ability to measure iron in the liver accurately (that is, with low error) could provide an early marker for HCC development, as HCC tumours are thought to typically contain less iron than the liver (iron sparing). However, previously iron in the liver could only be measured using biopsy. MRI provides a non-invasive tool to measure iron.
Current MRI techniques for measuring iron are not suitable for the application of detecting iron sparing as they are optimised to detect iron overload in diseases such as haemochromatosis and thalassemia. For iron sparing, low iron concentrations, and small, localised regions of differences in iron need to be detected.
In this thesis I highlight the various limitations with existing techniques and describe the optimisation process to develop methods to quantify iron sparing. I verified that these could potentially be used in iron sparing using healthy volunteer data, phantom data, and patients. These MRI techniques can now be used in clinical trials for assessing if iron sparing is indeed a feature of HCC and thus whether MRI could be used as a surveillance tool to detect iron sparing in patients at-risk of HCC.
The phonetics of labialized velars in Ancient Greek
Keywords: phonology
labiovelars
corpus linguistics
labialization
Zapotec
acoustics
acoustic perception
Ancient Greek
phonetics
philology
historical linguistics
coarticulation
sound change

This thesis investigates conditioned sound changes of Proto-Indo-European labialized velars *kw, *gw, and *gwh to labials, coronals, and velars in Ancient Greek. Acoustic and perceptual experiments in British English and Western Zapotec provide typological evidence to inform conclusions regarding the phonetic inception of the sound changes.
Before back vowels and consonants PIE labialized velars became labials in Ancient Greek. Two competing hypotheses have been proposed for these sound changes: perceptual confusion, in which e.g. *kw developed to /p/ via misperception due to acoustic similarity between the two stops (Ohala, 1989, 1993); and incremental articulatory change, in which e.g. *kw gradually developed to /kp/ and then /p/ (Whatmough, 1937; Garrett & Johnson, 2013). The acoustic studies here found little acoustic or perceptual similarity between /kw/ and /p/ in any vocalic environment, indicating that the latter explanation is more plausible.
Before front vowels PIE labialized velars became coronals. Philologists have proposed developmental pathways involving processes of incremental palatalization. This thesis finds evidence for coarticulatory fronting of the velar articulation of labialized velars in front vowel environments, but the effect is language-specific and its auditory prominence depends upon the durational overlap of the primary and secondary articulations. Increased auditory prominence of coarticulatory fronting in mid vowel environments may explain divergent developments of *gwh in Greek to labials before front vowels and to coronals before front mid vowels.
Before the back round vowel /u/ the PIE labialized velars lost contrastive labialization in Greek. The acoustic and perceptual experiments support a perceptual reanalysis account, in which contrastive secondary labialization of the velar is reinterpreted as coarticulatory rounding adjacent to a rounded vowel.
Charge transport layers and passivation for improved efficiency and stability of n-i-p perovskite solar cells
Keywords: metal-halide perovskite
perovskite passivation
charge-transport layers
n-i-p perovskite solar cells
solar cell stability

Perovskite solar cells have become a promising photovoltaic technology for harvesting energy from the sun. However, despite their low-cost processing and high performance, a few issues remain for their wider application. One of the main concerns is their stability. Commercializable solar photovoltaic technologies must remain stable under constant illumination and high-temperature not only for a few days as they would be tested in a lab, but for several years. In particular, low-cost, dopant-free, and stable hole-transporting materials need to be found to replace Spiro-OMeTAD, due to its instability issues. Furthermore, better passivation strategies need to be discovered and employed.

The primary aim of this project was to look for alternative charge-transfer materials to replace those typically used in a regular architecture solar cell device, and to make the perovskite absorber material more stable by additive engineering. To achieve this, various hole-conducting materials and passivation molecules were tested, and those which improved the film quality were further characterized and tested in devices for their performance and stability. The lessons learned from these studies led to the fabrication of a very stable solar cell architecture.

Chapter 4 focuses on a pair of alternative hole-conductors that are dopant-free and low in cost. They were found to perform just as well as spiro-OMeTAD whilst being more stable. Chapter 5 discusses an often-overlooked additive approach of applying aromatic amines to passivate the perovskite absorber. Our average benzylamine-modified perovskite devices maintained 80% of their initial efficiency over 2,400 hours in a 65°C 1 sun aging test. Meanwhile, the average control devices without additives degraded to 45% of their initial efficiency. Chapter 6 investigates the potential of applying a fullerene-based self-assembling monolayer to stabilize the electron-transporting layer/perovskite interface. However, the results of the fullerene self-assembling monolayer-modified interface were less stable. Despite that, the reasons for their instability were investigated and a future research direction is proposed to improve them.

The novel charge-transporting materials and bulk/interface modifications studied in this thesis are promising solutions for stabilizing the regular architecture of perovskite solar cells. Moreover, the investigation into why certain passivation methods work and others fail can help us design and select better materials and passivation methods for more durable solar cells.