VictorJuiz/thesis huggingface dataset:
How could shared patient experience support the process of decision-making in starting insulin therapy in non-insulin-treated adults with type 2 diabetes in the UK?

Background: Many individuals with type 2 diabetes are reluctant to accept insulin treatment. As a complementary resource to formal support, an intervention based on shared patient experience might be able to facilitate such a process. Presently, however, there are many uncertainties about the evidence to support the pragmatic use of shared patient experience.
Methods: Several research techniques were used to examine these issues. A review of existing systematic reviews was conducted to clarify the idea of shared patient experience in a context of type 2 diabetes management in general. Second, a systematic review explored the impact of shared patient experience on health in adults with type 2 diabetes. Third and fourth, two linked studies, a narrative literature review of qualitative studies and a secondary analysis of an existing collection of qualitative interviews examined patients’ attitudes, experiences, information/support needs in relation to the initiation of insulin therapy. Fifth, a primary qualitative study investigated patients’ views and preferences toward the use of shared patient experience to support the process of decision-making in starting insulin. Finally, a proposed intervention design was developed based on all the evidence provided by the previous studies.
Results: More new knowledge was contributed to the field of shared patient experience in diabetes care by identifying a working definition of shared patient experience, some common components of shared patient experience and some studies highlighting the evidence of the effects of shared patient experience on disease-related health in type 2 diabetes. It also revealed the patients’ reluctance about moving onto insulin, concerns about the lack of communication about insulin with their healthcare providers prior to insulin, a range of valuable potential shared patient experience has to help patients in the decision-making process, and the patients’ preferences about different formats of shared patient experience. This evidence suggested that shared patient experience, delivered though a face-to-face one-to-one discussion and/or an online curated collection of the filmed narrative interview material conveying certain key elements of peers’ stories, could be an appropriate, efficient and acceptable way to deliver such an intervention in the context of insulin decision-making in type 2 diabetes.
Conclusion: There are still many patients being left with psychological concerns about insulin and without sufficient support to overcome such concerns, suggesting a need for additional support which can be delivered as a supplement to formal support provided by healthcare professionals. Shared patient experience could be one of the potential strategies to help ease the process of insulin decision-making.

Keywords: diabetes
shared patient experience
peer support
insulin
Advisor: Farmer, A
Locock, L
Multisensory decision-making: Spatiotemporal dynamics and computational principles

Humans have evolved to fuse information across senses by weighing the reliability of each modality (e.g., a viewer relies more on the picture to follow a drama if the TV audio is faulty; Ernst & Banks, 2002) as well as to infer unseen causes of sensory events by inverting internal generative models of the world (causal inference or CI: “Was the film dubbed or not?”). These multisensory strategies resemble Bayesian inference, but the mechanism whereby the inference unfolds step-by-step in a biologically plausible fashion remains poorly understood. Moreover, the reliability-weighted fusion and CI strategies have complementary costs and benefits, but sometimes seem to describe human choices in experimental conditions that presumably only satisfy the assumption of each particular strategy (e.g., De Winkel, Katliar, & Bülthoff, 2015; Meijer, Veselič, Calafiore, & Noppeney, 2019).
In this thesis, I present converging evidence, from a series of human neuroimaging and psychophysics studies, suggesting that these rival accounts of multisensory inference can be reconciled by a time-resolved mechanism: The brain rapidly derives a fused sensory estimate for computational expediency and, later and if required, filtering out irrelevant signals based on the inferred sensory cause(s).
First, analysing time- and source-resolved human magnetoencephalographic data (chapter 2), I unveil a systematic spatiotemporal cascade of the relevant computations for multisensory inference, starting with early segregated unisensory representations, continuing with sensory fusion in parietal-temporal regions, and culminating as CI in the frontal lobe. This suggests that the distinct computations required for flexible multisensory behaviour (fusion and CI) coexist, but each dominates at different times and in distinct regions (chapter 3).
Furthermore, using behavioural paradigms such as speeded-judgement under deadline-induced time pressure as well as psychophysics leveraging sensory masking (chapter 4), I explicitly quantified how the unfolding of neural representations can be read out to drive behaviour. Collectively, slower versus faster behavioural choices reflect more of CI versus sensory fusion, respectively, indicating that the mapping from neural representational activity to behavioural choice corroborates the temporal hierarchy revealed in the neural data.

Keywords: Structure inference
Decision-making
Prefrontal cortex
MEG
Flexible behaviour
Magnetoencephalography
Parietal cortex
Causal inference
Computational model
Multisensory integration
Multisensory computation
Representational similarity analysis
Advisor: Summerfield, C
Kayser, C
Spence, C
Topics in the theory of p-adic heights on elliptic curves

This thesis deals with several theoretical and computational problems in the theory of p-adic heights on elliptic curves.
In Chapter 3 we provide a new algorithm for the computation of the Mazur--Tate p-adic height in a family of elliptic curves over the rationals. As an application, we study the conjectural non-degeneracy properties of the pairing induced by the height, as well as orders of vanishing and arithmetic interpretations of some of the coefficients of the regulator series.
In Chapter 4 we use the decomposition of the p-adic height as a sum of local contributions to explore a number of problems related to the quadratic Chabauty method for determining integral points on hyperbolic curves. For instance, we remove the assumption of semistability in the description of the quadratic Chabauty sets X(Zp)2 containing the integral points X(Z) of an elliptic curve of rank at most 1. Motivated by a conjecture of Kim, we then investigate theoretically and computationally the set-theoretic difference X(Zp)2\X(Z)
In Chapter 5 we describe an implementation of the Chabauty--Coleman method for genus 3 hyperelliptic curves over Q whose Jacobians have rank 1. This is used to compute the rational points on approximately 17,000 curves and to provide evidence for a conjecture of Stoll.
In Chapter 6 we extend the explicit quadratic Chabauty techniques to compute integral points on elliptic curves and rational points on genus 2 bielliptic curves to general number fields.
Finally, in Chapter 7 we prove that the first two coefficients in the series expansion around s=1 of the p-adic L-function of an elliptic curve over the rationals are related by a formula involving the conductor of the curve.
The introductory Chapter 1 outlines the common themes of the thesis; Chapter 2 introduces some preliminary notions.

Advisor: Balakrishnan, J
Lauder, A
Design of a TIMP-3 mutant with an increased half-life for improved protection against cartilage breakdown

Osteoarthritis (OA) is a degenerative joint disease for which there are currently no disease-modifying drugs. OA is characterised by degradation of cartilage extracellular matrix (ECM) components by catabolic metalloproteinases. Tissue inhibitor of metalloproteinase 3 (TIMP-3) is the endogenous inhibitor of these enzymes, and thus a target for the development of novel OA therapies. Extracellular levels of TIMP-3 are regulated by endocytosis via the scavenger receptor LDL receptor-related protein-1 (LRP-1), reducing its in vivo half-life and chondroprotective activity. The aim of this study was to generate a TIMP-3 mutant resistant to LRP-1 binding but with unaltered affinity for target metalloproteinases and ECM glycosaminoglycans, since we hypothesised such a mutant would have increased chondroprotective activity. LRP-1 ligand-binding motifs have been proposed to consist of a pair of surface lysine residues separated by 21Å. Using in silico molecular modeling of a proposed TIMP-3 structure, we identified 10 pairs of lysine residues potentially satisfying this motif. Site-directed mutagenesis of all of these lysine pairs to alanine generated TIMP-3 mutants with resistance to LRP-1-mediated endocytosis, localising the LRP-1-binding residues to an extended basic patch on the TIMP-3 surface.
TIMP-3 K26A/K45A and TIMP-3 K42A/K110A were further analysed. TIMP-3 K42A/K110A had unaltered affinity for target metalloproteinases, but markedly reduced affinity for ECM glycosaminoglycans. It displayed improved chondroprotection over 24 hours, but was no more effective than Wild-type TIMP-3 over longer time periods, possibly due to its inability to be retained on the ECM. TIMP-3 K26A/K45A, on the other hand, retained high affinity for both target metalloproteinases and ECM glycosaminoglycans, and was found to have a longer half-life in cartilage and improved chondroprotective activity relative to Wild-type TIMP-3. This study thus identified an LRP-1-resistant mutant of TIMP-3 with an increased half-life and protective activity in cartilage, and showed that such behaviour was dependent on maintenance of interaction with the ECM. A similar paradigm may apply to other ECM-associated LRP-1 ligands.

Advisor: Troeberg, L
Nagase, H
#Voteleave or #Strongerin: resonance and rhetoric in the EU referendum

This thesis explores the persuasive function of tweets in the context of the 2016 European Union membership referendum. What makes a message resonate with its audience on social media? How can the message be expressed and delivered most effectively? What strategies do individuals and organisations use when they send a tweet and why?
To explain tweet success, or resonance, an interdisciplinary framework centred around rhetoric was established. It is comprised of nine different features: discoverability, organisational authority, message framing and structure, emotions, topical issues, resolution, questions, and playfulness.
A multi-method design is adopted to address the research questions from micro- and macroscopic perspectives. Approximately 9.8 million referendum-related tweets were collected from Twitter during the referendum period (15 April-22 June 2016). A random sample of 2,976 was hand-coded according to the framework. Semi-supervised algorithms were used to label the features in the full dataset, and multivariate regressions were computed to assess the influence of each feature. This quantitative analysis is complemented by interviews with 22 campaign leaders, journalists, politicians, digital marketing experts, and private individuals who tweeted actively during the referendum. Interviewees included the CEOs of Vote Leave and Stronger In, BuzzFeed’s Europe Editor, a Twitter board member, and a former MP and Minister of State for Europe. Finally, exceptional tweets and users were identified from the regression models and interview data and rigorously scrutinised.
The overarching conclusion is that in the fast-paced and high-volume landscape of social media, discoverability is more important for resonance than content or style. Increasing the likelihood that a message is seen matters more than what is said or how it is said, because the vast majority of tweets are not seen. As such, this thesis introduces a revised schema for the resonance of digital cultural objects premised upon algorithmic power, visual media, and organisational authority.

Keywords: EU referendum
Natural language processing
Internet linguistics
Political campaigning
Digital rhetoric
New media
Brexit
Social media
Twitter
Discourse analysis
Advisor: Blank, G
Bright, J
A general-purpose model for emulating expression-based high-throughput assays

High-throughput assays (HTAs) are the gold standard for scientific experimentation, providing starting points for drug design, for understanding the interactions between genes in biochemical cascades, and for identifying the role of genetic variants in the broader context of cellular processes. Here, I introduce a widely applicable and practically usable deep neural architecture that can recapitulate expression-based HTAs. Trained solely on promoter elements, the model can learn to emulate the transcriptional machinery of a given cell type or tissue – allowing us to construct in silico DNA reporter assays, predict the transcriptomic impact of small molecules in cell lines, and infer regulatory networks. By leveraging the tissue-specific properties of the model, I further show how model-derived impact scores can pinpoint functional tissues underlying complex traits, outperforming methods that depend on colocalization of eQTL and GWAS signals. I subsequently demonstrate the utility of this model in investigating the role of DNA and histone modifications in difficult-to-study processes, such as neural induction. Using an extension of the same architecture, I show how the framework outperforms linear models in predicting the consequences of genotype variation. I use the framework to identify putatively functional eQTLs that are missed by experimental high-throughput approaches that characterise variant function. By emulating the transcriptional machinery of human tissues/cells, this represents one of the first attempts to recapitulate expression-based HTAs using a single in silico framework. I also introduce a new analytic strategy that leverages coexpression differential dependence networks (i.e. correlation perturbation between gene clusters) to model the effects of genetic variation in a tissue-dependent manner, and to subsequently, discover new loci for type 2 diabetes-related traits. I demonstrate that the newly discovered risk loci are driven by tissue-specific differential dependence network annotations and as validation, highlight how they have been confirmed in (larger) genetic studies for the same or closely-related traits and/or partially verified experimentally. My results are a first step towards my long-term goal of developing a general-purpose model that can learn to predict expression under any set of arbitrary constraints (e.g. for a tissue of interest, given a particular genotype, or after a fixed-time post-drug exposure) and demonstrate the utility of such strategies in decoding GWAS signals.

Advisor: McCarthy, M
Holmes, C
Neuroanatomical scaling, neurotopography of gene expression, and sex chromosome aneuploidy

The publication of topographically-defined, whole-transcriptome quantifications in the human brain has created the opportunity to mine the association of imaging findings with genetic data. An increasingly popular analysis is to connect groupwise anatomical differences in imaging space with differential expression of genes as defined by their topographical expression across the cortical mantle.
This thesis uses this approach to address two problems in neuroimaging: 1) total brain size normalization and 2) association of anatomical changes with gene expression in health.
The thesis begins by examining surface area scaling in the cortex and subcortex. It describes the regions of non-linear surface area scaling in both compartments --- and claims those foci of non-linear scaling may pose challenges for the analysis of disease.
Next, the thesis considers the biological meaning of surface area scaling in the cortex by comparing regions of non-linear scaling to known maps of developmental and evolutionary expansion --- among others. A spatially sensitive bootstrapping procedure is introduced to quantify similarity or disimilarity amongst cortical maps.
Lastly, this thesis applies a scaling-sensitive normalization framework for total brain size differences in the analysis of a neurogenetic disease cohort. In particular, scaling-sensitive analysis of the striatum, thalamus, and globus pallidus in Sex Chromosome Aneuploidy results in increased specificity for disease specific anatomical changes in both nucleus volume and shape.

Advisor: Lerch, J
Forward to the past: regression in Galatians

Paul’s letter to the Galatians indicates not only that his Gentile readers stand on the brink of Jewish proselyte conversion but that compliance will involve returning to the norms of their pagan past (Gal 4.8-9; 5.1). In what sense can this possibly be true?
This thesis accords Paul’s warnings about regression greater significance in his argument than has previously been acknowledged, and finds existing explanations (Paul’s readers had substantial past exposure to Judaism, he played the regression card merely for rhetorical effect etc.) inadequate. None of these alternatives explains the striking difference between Paul’s tolerance of law-observance among Jews (Gal 2.6-10; 5.3, 6; 6.15) and his insistence upon its dangers among Gentiles.
On the basis of a thorough and original study of Graeco-Roman and Jewish backgrounds in central Anatolia and characterisations of Gentile religion and the weaknesses associated with it in Paul (e.g. 1 Cor 8.1-13) and in his wider Jewish milieu, I propose that his regression terminology reflects a concern about the enduring magnetism and intuitive plausibility of his readers’ entrenched religious presuppositions.
Interpreting στοιχεῖα τοῦ κόσμου in Gal 4.3 as basic elements of religious behaviour common to Judaism and paganism but implemented with different motives and significations in each case, I argue that exposure to these elements through the medium of Jewish observances was reawakening assumptions associated with them in the Galatians’ pagan past.
Reading ‘enslavement under the στοιχεῖα’ in Galatians 4 as equivalent to ‘imprisonment under in the law’ and ‘life under the curse’ in Galatians 3, and noting that belief in the possibility of justification by works is limited to Gentiles in Gal 2.15-16, I argue that pagan, and not Jewish, presuppositions about the efficacy of works in divine-human interactions emerge as the foil against which the letter’s call to action is designed to make sense.

Keywords: faith and works
Galatians
accommodation
Gal 4.8-11
Paul
Paul within Judaism
new perspective
στοιχεῖα
Pauline theology
regression
stoicheia
Advisor: Bockmuehl, M
Dissecting the role of MukF in the chromosome organisation by Escherichia coli MukBEF

The organisation and segregation of chromosomes from all domains of life are mediated by the architecturally conserved Structural Maintenance of Chromosomes (SMC) proteins and their accessory factors. In Escherichia coli, the distantly related complex MukBEF retains the distinctive tripartite ring structure that has been proposed to topologically entrap DNA. Cyclical loading and unloading of DNA is regulated by ATP binding and hydrolysis, both of which are essential for SMC function. The kleisin MukF stimulates MukB ATPase activity. Uniquely, MukF forms stable dimers through the N-terminal Winged Helix Domain (WHD), thus potentially allowing for the formation of higher order complexes. Null mutations in any one of the mukBEF genes results in temperature sensitivity in rich media, disturbed organisation of the chromosome and anucleate cell production even under permissive conditions.
In this study a tripartite approach of biochemistry, genetics and in vivo imaging, provides insight into the functional importance of dimeric MukF. I have identified hydrophobic interactions between protomers that contribute to MukF dimerisation. In vitro assays show that full length MukF monomers are folded and stimulate MukB ATPase to wild type levels. However, in vivo, MukF dimerisation is essential for MukBEF function, as judged by the ΔMukBEF phenotype of temperature sensitivity in growth on rich media. Epifluorescence image analysis and Photoactivatable Localisation Microscopy (PALM) data indicate that chromosome interaction of MukBEF complexes formed with monomeric MukF is defective. Furthermore, an artificial dimerisation domain fails to rescue the ΔMukBEF phenotype. I propose that the formation of dimers of dimers is a prerequisite for the ability of MukBEF to transport chromosomal DNA by a “rope-climber” model and that the dimerisation domain may play a dynamic role in the coordination of MukBEF complexes.

Advisor: Sherratt, D
Negotiating youth deviance and parenting: exploring the effects of social class in professional interactions

Recently, socially decontextualised understandings of youth crime as triggered by individual and familial risk factors have anchored themselves in criminological theory and the UK’s youth justice practice. At the same time, research has exposed classed selection effects of institutions that propel behaviourally challenging young people and their parents into the system not only based on the seriousness of their cases, but also according to the family’s reputation and their social disadvantage. As such effects remain largely unexplored, this thesis aims to analyse the processes behind agency contact, and examine how they could be directing individuals of diverse social locations on different pathways. It employs participant observation, semi-structured interviews, and focus groups to gather the views of young people, their parents, and practitioners on whether, how and why interactions between professionals and their clients might differ according to social class and with what consequences. Drawing mainly on Bourdieu’s critical sociology, Emerson’s work on negotiated trouble, Sayer’s moral understanding of class, and Boltanski and Thévenot’s polity model to make sense of the data, the thesis finds that a family’s social location, institutional discourses, and organisational rules within youth justice and children’s services all affect the views of practitioners and how they respond to children’s conduct and parents’ childrearing.

Keywords: children's services
negotiating trouble
habitus and field
social class
polity model
parenting
youth justice
youth deviance
professional interactions
moral understanding of social class
Advisor: Condry, R
Measurements of simplified template cross sections in the H→WW* decay and interpretations with effective field theory

This thesis discusses the measurement of the Higgs boson production cross-sections in the H→WW*→ eυμυ decay channel and the Effective Field Theory (EFT) interpretations of combined Higgs boson measurements. The results are obtained using 36 fb-1 proton-proton collision data produced at the Large Hadron Collider at a centre-of-mass energy of 13 TeV, and recorded by the ATLAS detector in 2015 and 2016. The measured H→WW* cross-sections are defined within the Simplified Template Cross Sections (STXS) framework, where the gluon-gluon fusion (ggF) and vector boson fusion production modes are studied. In the case of the ggF production mode the cross-sections are measured as a function of transverse momentum and number of jets. With the H→WW* measurements high transverse momentum can be accessed, which is sensitive to new physics. Seven cross-section measurements with the STXS framework are perfomed using the H→WW* decay. This thesis also presents the first ATLAS EFT interpretation of combined Higgs boson data in H→γγ and H→ΖΖ* →4l channels. Finally, the EFT interpretation is also performed including measurements from the H→γγ, H→ΖΖ* → 4l, and H→WW* channels. The constraints are obtained on the EFT parameters sensitive to modifications of the Higgs boson couplings to strong and electroweak gauge bosons, and to the top quark.

Advisor: Becker, K
Issever, C