VictorJuiz/thesis huggingface dataset:
Deep learning with limited labelled cardiac data

Cardiac data, that which pertain to the heart, are a rich source of information that reflect a patient's cardiac status. Extracting clinically-useful insight from such data can be achieved via deep learning, a sub-field of artificial intelligence. Current clinical deep learning algorithms, however, are heavily dependent upon resources such as abundant data and high-quality annotations, both of which are scarce in many clinical settings. In low-resource settings, for example, the prohibitively high cost of medical infrastructure precludes the collection of data and the limited number of physicians hampers the provision of annotations. The reasons for data paucity in high-resource settings are multi-fold, ranging from stringent patient-privacy regulations to the low inter-operability of medical records. Physicians in this setting can also be disengaged due to the overwhelming number of annotation requests.
To address this challenge, in this thesis, we design deep learning algorithms that exploit cardiac data to achieve more with less; less data, fewer labels, and less medical supervision during the learning process. While designing these algorithms, we focus predominantly on the clinical task of cardiac arrhythmia classification, which involves diagnosing abnormalities in the functioning of the heart.
We deploy our algorithms in three paradigms characterized by an incrementally increasing level of resource availability. In Part I of the thesis, we simulate a low-resource scenario with limited data and exploit conditional generative adversarial networks to generate cardiac time-series data for augmentation purposes. In Part II, we simulate access to abundant unlabelled data and limited labelled data. In this environment, we propose an active learning framework that dynamically determines whether an annotation should be requested from a physician or generated by an algorithm instead. We also present a family of patient-specific contrastive learning methods that improve resource-efficiency; the ability of a learner to solve a task with less data. In Part III, we deal with more extensive multi-modal data. We explore the degree to which algorithms suffer from catastrophic forgetting (the impaired ability to solve tasks from the past upon learning tasks in the present), and propose a continual learning framework to overcome this phenomenon. We also simultaneously exploit cardiac data and clinical textual reports to design a captioning system that, upon receiving cardiac signals, generates clinical reports in multiple languages.
By designing such resource-efficient frameworks, we hope to improve the accessibility of clinical deep learning algorithms, and, in turn, healthcare to vulnerable patients in low-resource settings.

Keywords: Continual Learning
Active Learning
Contrastive Learning
Representation Learning
Generative Learning
Captioning
Cardiac Data
Electrocardiogram
Healthcare
Deep Learning
Advisor: Clifton, D
Zhu, T
Platinum-lanthanide metallodrugs for imaging and therapy

This work describes the development of several Lanthanide-Platinum complexes and outlines the application of the products as theranostic agents. The luminescence and relaxivity properties of the complexes is investigated for imaging purposes and the cytotoxicity of the complexes is exploited for therapeutic use.
Chapter 1 discusses the fundamental properties of lanthanides and platinum. For lanthanides, the discuss focuses on their luminescence, magnetism and stability. As for platinum, the discussion focuses on the properties that relates to its cytotoxicity, such as cellular uptake. A brief literature review on Ln-Pt theronostic complexes is given.
Using the CuAAC reaction to conjugate Ln and Pt building blocks is described in Chapter 2. Another type of click reaction-SPAAC is utilised in Chapter 3. The photochemical properties of the clicked Pt complexes are studied thoroughly. The purification and characterisation of Ln-Pt complexes are also investigated.
Chapter 4 describes a series of cell-permeable Ln-Pt complexes, of which the relaxivity and cell diffusion NMR of the Gd complexes were studied and the photophysical properties of the switch-on Eu complexes was also investigated.
Chapter 5 delineates the conclusion and chapter 6 provides experimental procedures.

Keywords: theranostic
lanthanide-Platinum
Advisor: Farrer, N
Faulkner, S
Modelling rhizobial metabolism in rhizobium-legume symbioses

In this work, metabolic modelling approaches were combined with experimental datasets to elucidate rhizobial metabolism in rhizobium-legume interactions. First, a genome-scale metabolic model for Rhizobium leguminosarum bv. viciae 3841 (Rlv3841) was reconstructed and validated. Integration of transcriptome, proteome, metabolome and gene essentiality data was performed to obtain models specific to rhizosphere bacteria, undifferentiated nodule bacteria and nitrogen-fixing bacteroids. Analysis of these models revealed the importance of leucine, polyphosphate and AICAR synthesis in the rhizosphere and indicated that myo-inositol catabolism is specifically active in undifferentiated nodule bacteria. The bacteroid model predicted active synthesis of histidine as well as uptake of a pentose sugar in addition to dicarboxylates, which are the main carbon sources for bacteroids.
Next, a reduced model of bacteroid metabolism was obtained using experimental datasets for Rlv3841. Computational methods that do not require the specification of nutrient uptake rates were applied to investigate properties of bacteroid metabolism based on a minimum number of assumptions. Analysing the effect of oxygen availability on central carbon and nitrogen metabolism suggested that both carbon polymer synthesis and amino acid secretion by bacteroids function to facilitate carbon and redox balance under the microaerobic conditions required for nitrogen fixation. The model further predicted that low oxygen levels restrict flux through the decarboxylating tricarboxylic acid cycle arm, which would limit ammonia assimilation by bacteroids and thus constitute a fundamental prerequisite for a productive symbiosis. Model predictions were supported by experimental measurements of oxygen uptake rates and NADH/NAD+ ratios as well as metabolic flux analysis.
Finally, a comparison of bacteroid metabolism for different rhizobial strains was performed to evaluate differences and similarities of symbioses between Rhizobium and Sinorhizobium strains and various host plants. Genome-scale metabolic models for six different rhizobium-legume symbioses were reconstructed and reconciled, and bacteroid models were obtained through integration of gene expression data. The models were able to correctly identify strain- and symbiosis-specific differences in the pathways that are used for pyruvate synthesis. In addition, significantly lower metabolic activity and symbiotic efficiency were predicted for reversibly differentiated bacteroids compared to terminally differentiated bacteroids, which is consistent with experimental evidence.

Keywords: rhizobium
symbiosis
metabolic modelling
Advisor: Papachristodoulou, A
Poole, P
Slowing the spread: assessing early Covid-19 intervention effectiveness in São Paulo using socio-demographic and mobility data

Background and Motivation: The COVID-19 pandemic continues to have devastating health, social, and economic impacts around the world. Brazil ranks second globally in COVID-19 deaths, with spiraling growth after its first case in the Metropolitan Region of S ̃ao Paulo (MRSP), the largest urban agglomeration in South America. Lockdown interventions to reduce mobility are a leading tool for infection mitigation, and while effective on aggregate, their adherence is impacted by socio-demographic factors. A forward-looking model that evaluates the ability of lockdowns to slow disease spread through a socio-demographic lens can inform more equitable policy-making.
Methods: Cellphone mobility data integrated with traditional commuting survey, census, and COVID-19 data from the MRSP are used to develop a novel effective distance-based model to measure the ability of lockdowns to slow disease spread. This Infection Delay Model (IDM) is applied to simulated epidemics across the MRSP. The first analysis clusters regions-at-risk that benefit similarly from lock-downs. The second analysis identifies outbreak regions where interventions lead to high and low slowdowns for the rest of the MRSP. Socio-spatial context provides meaningful and actionable interpretations of lockdown effectiveness.
Results: For regions-at-risk, the clustering analysis reveals that socio-demographically vulnerable regions with lower centrality have greater delays to their first case by early lockdowns. The second analysis, observing each region as an initial source of infection, reveals that outbreaks beginning in socio-demographically secure regions with higher centrality are disproportionately slowed by lockdowns to the rest of the MRSP.
Conclusion: A fundamental relationship exists between social inequality and the ability of lockdowns to slow infection spread. First cases in socio-demographically vulnerable regions can be most delayed by early lockdowns, conveying that rapid interventions can reduce health inequities. The outbreak analysis shows that lock-downs slow the spread more for outbreaks beginning in more secure regions. Increasing capacity of vulnerable regions to isolate can strengthen the MRSP’s resilience to future outbreaks.

Keywords: Inequality
Public Policy
Socio-Demographic Inequality
Unsupervised Learning
Human Mobility Data
Spatial Analysis
Epidemiological Modelling
Advisor: Taylor, G
Camargo, C
The complement system and invariant natural killer T (iNKT) cell responses

The recent discovery of intracellular complement activation, specifically anaphylatoxin generation and downstream autocrine receptor engagement in conventional α/β CD4+ T cells has provided new insights into mechanisms of T cell activation, polarisation, and homeostatic survival. Anaphylatoxin generation by antigen-presenting cells (APCs) which leads to paracrine signalling via anaphylatoxin receptors on T cells has also been observed but is less extensively described. It is speculated that cell-derived complement may also influence the activity of non-conventional α/β T cells, specifically invariant Natural Killer T (iNKT) cells. The modulation of iNKT cell effector function by cell-derived complement may manifest in two ways, either through autocrine signalling events or via paracrine signalling by neighbouring APCs. Through a combination of molecular biology approaches, a thorough appraisal of iNKT complement expression profiles was performed. Specifically, iNKT cells were shown to up-regulate C3 and the anaphylatoxin receptors C3aR and C5aR1 on their cell surface upon activation with the canonical ligand α-GalCer. Moreover, iNKT cells may ‘recycle’ C3 from the extracellular space, to potentially regulate complement in their local microenvironment. As iNKT cells mature dendritic cells (DC) in a CD40L-dependent manner, subsequent work showed that engagement of the CD40-CD40L axis also influenced DC complement expression profiles. Specifically, the alternative pathway (AP) complement protein Factor B (FB) along with C3 were positively modulated by CD40 ligation. Moreover, pharmacological inhibition of FB by proprietary GSK inhibitors, specifically cell-permeable small molecules was shown to suppress DC effector function. Subsequent work which assessed cell-derived anaphylatoxin generation was undertaken to validate the specificity of pharmacological inhibition. In conclusion, potential crosstalk mechanisms between the CD40- CD40L axis and FB may underscore DC activation profiles. Modulation of DC effector function may in turn influence iNKT activation at the iNKT-APC interface.

Advisor: Salio, M
Kolev, M
Davis, S
A new model for the delivery of psychiatric services for general hospital inpatients: the development and delivery of a psychiatric service model for older, acutely admitted general hospital inpatients

Background
Current psychiatric services for general hospital inpatients have limitations in meeting the needs of increasingly elderly and multimorbid populations. New service models are emerging, but lack evidence of effectiveness from randomised trials. I aimed to establish the evidence for current psychiatric services for general hospital inpatients, and develop, operationalise and deliver a new service model for delivery and evaluation in a randomised trial, The HOME Study.
Methods
A systematic review of randomised trials of psychiatric services for general hospital inpatients was completed. A new service model was developed by reviewing relevant literature, obtaining feedback from clinicians and patients, and iterative piloting. The new model was operationalised for consistent delivery in the trial. The delivery of the resultant model in the trial was evaluated using the RE-AIM framework.
Results
The systematic review identified eight eligible randomised trials. No trial reported evidence that the psychiatric service was more effective than usual care. A new psychiatric service model for older general hospital inpatients, Proactive Integrated Psychological Medicine (PIPM) was developed. The model was described in a service manual, and a checklist and quality assurance process were developed to maximise consistent delivery. PIPM was implemented in three hospitals in southern England, over two years. 1,373 (99%) of patients randomised to PIPM received the intervention. PIPM was delivered in accordance with the service manual, with six out of seven measures of concordance with the service manual over 94%. Interviews were conducted with patients (n = 26) and carers (n = 18), ward professionals (n = 55), and all PIPM clinicians (n = 15). Thematic analysis identified an appreciation of the increased psychiatric presence on the ward, common among all interviewee groups. However, PIPM clinicians and ward professionals were concerned PIPM may blur professional responsibilities on the ward, potentially resulting in confusion for patients.
Conclusions
There is no randomised evidence that current psychiatric services for general hospital inpatients are effective. A new service model, PIPM, has been developed with clinicians and patients, based on the best available evidence. PIPM was delivered largely as intended in a large randomised trial, The HOME Study. The outcome of The HOME Study will provide further information on the effectiveness of PIPM and indicate the value of further implementation.

Keywords: general hospital
proactive integrated psychological medicine
service development
psychiatry
RCT
psychological medicine
systematic review
liaison psychiatry
Advisor: Sharpe, M
Walker, J
Layperson, ascetic, and cleric in Iberian Christianity, c.500-711

We tend to see late antique and early medieval Christianity through a clerical lens. This is particularly true in the Iberian Peninsula, with its highly episcopal and legalistic source base. The Suevic and Visigothic kingdoms both saw ambitious projects of state formation marked by doctrinal unification and the confluence of ecclesiastical and royal structures of power. In the Visigothic kingdom, the exceptional literary production of Isidore of Seville has been characterized as indicative of a ‘Renaissance’ in Christian culture, clerical organization, and pastoral care. I show, however, that Iberian Christianity should be understood in a much more decentralized and fragmentary manner. Turning away from paradigms of Christian state formation, ‘the church’ appears as a much more complex, and conflictual entity, rooted more in local contexts than top-down structures. I argue that questions of hierarchy within the ecclesia itself—the distinction between the clergy and laity, or between ascetic ideals and the ‘worldly’ elements of Christian organization—were key factors in the emerging structure of post-Roman medieval Christian societies. Subjecting the notion of ‘the church’ itself to historical scrutiny, I render visible the important role of actors outside of the formal clerical hierarchy in matters of religion, and show the persistent fragility of episcopal structures, rooted as they always were in local contexts. Overall, what emerges is a view of Iberian Christianity in which the apparent institutional high point of the Visigothic seventh century is less pronounced, and the long-term significance of persistent tensions within the ecclesia comes to the fore.

Keywords: asceticism
late antiquity
ecclesiology
lay religion
Iberian Peninsula
Advisor: Leyser, C
Cultural identity and multilingualism in South Tyrol from 1919 to 2019

This thesis concerns the multilingual border province of South Tyrol, annexed by Italy in September 1919 following the collapse of the Austro-Hungarian Empire. It covers the period between 1919 and the centenary of the annexation in September 2019.

The primary research questions are:
a) Is it possible to speak of a South Tyrolean cultural identity and, if so, how can it be defined?
b) What is the precise nature of South Tyrol’s multilingualism and its impact on South Tyrolean cultural identity?

The thesis uses an external perspective – independent of the individual language groups in South Tyrol – to explore the tensions between competing views of the province as a haven of multilingualism, a province irreconcilably divided along cultural and linguistic lines, or a transit land between Italy and the German-speaking world. The thesis examines how far the distinctiveness of the three main language groups – German, Italian and Ladin – precludes their influence on each other. It considers the differences within language groups, looking at how different identities can co-exist as part of the same broad language community. It brings together fictional and non-fictional written contributions, oral interventions, and artefacts of memory culture to model an approach to debates on cultural identity and multilingualism which integrates the perspectives of groups and individuals that have previously not been addressed in detail or only in isolation from the broader discussion.

The thesis argues that in order to develop an understanding of cultural identity in South Tyrol, it is necessary to analyse the particular constellation of factors which affect the cultural identity formation of the individual groups, their interactions and their development over time. These include geographical factors, historical and political factors, cultural and social factors, and not least the linguistic and literary expression of the different groups that participate in the province of South Tyrol.

Keywords: Italian studies
multilingualism
German studies
South Tyrol
cultural identity
Advisor: Kohl, K
Bonsaver, G
Besov functional calculus for two commuting operators

The subject of this dissertation is the construction of a functional calculus for functions of two variables and pairs of commuting operators.
Analytic Besov functions in one variable in the context of operator theory appeared in the works of Vladimir V. Peller, Steven White, and Pascal Vitse. More recently, Charles Batty, Aleander Gomilko, and Yuri Tomilov offered a novel and unifying approach to constructing a functional calculus for the generators of bounded semigroups on Hilbert spaces and generators of bounded holomorphic semigroups on Banach spaces. Our main aim is to extend the latter construction to the setting of two commuting operators.
We begin by providing an overview of the basic theory of one-parameter strongly continuous semigroups, and the theory of Besov functional calculus in one variable. We establish a new result concerning the spectral features of the one-dimensional Besov calculus, and show that compositions of certain functions are in the one-dimensional Besov class, B
.
We define and characterise a two-dimensional analogue of the class B
, denoted by B2
, and show that it shares many desirable characteristics with its one-dimensional counterpart. We prove that the class B2
is a Banach algebra containing the two-dimensional Hille-Phillips algebra as its proper subspace, and discuss some of its topological properties. We obtain a number of results on spectral decompositions and provide useful approximation techniques. We show that all functions in our class enjoy representations given in terms of a partial duality, and prove a convergence lemma for sequences of functions in the class.
We then construct a two-dimensional functional calculus for pairs of commuting semigroup generators and functions in the class B2
. We show that our construction yields a bounded algebra homomorphism. We demonstrate that the resulting calculus extends the two-dimensional Hille-Phillips calculus, that it is compatible with the joint holomorphic and half-plane calculi, and consistent with the Besov calculus for functions in one variable. Finally, we obtain a spectral mapping theorem, and establish that our calculus is essentially unique.

Keywords: functional calculus
Besov algebra
semigroup generator
sectorial operator
Advisor: Batty, C
Seifert, D
Martial Book XII : a commentary

The commentary consists of an introduction and individual line by line commentaries on the prose preface and the 98 epigrams. The introduction comprises a brief discussion of the dating of book 12, its distinctively Spanish elements, and the arrangement of the poems, and a more detailed treatment of the textual tradition of Martial. The commentary addresses matters of textual, literary and social-historical interest as they arise, and provides a large quantity of parallels on points of usage. It attempts in particular to identify and explain the point of the comic poems, both as jokes and as literary works. It also examines poems in their relation to the rest of book 12 and to the whole of Martial's opus. A select bibliography is appended.

Keywords: Epigrammata Liber XII
Martial Book XII
Rome
Martial Book 12
Epigrammata Liber 12
Epigrams
Latin
Bistable turbulent transport in fusion plasmas with rotational shear

Turbulent transport is a major limiting factor for the energy yield of magnetic- confinement fusion experiments. Turbulence is driven by gradients in the profiles of equilibrium plasma parameters, and it can be regulated by the presence of sheared flows. Direct numerical simulations of turbulent transport are challenging because of the broad range of temporal and spatial scales characterising fusion plasmas. In this thesis, a novel algorithm is developed to include an externally imposed, mean rotational flow shear in linearly implicit, local δf gyrokinetic codes. Unlike the discrete-in-time approach currently followed by a number of codes, it treats flow shear continuously in time, allowing for sparser numerical grids to be used. In some cases, the new algorithm leads to a difference in the level of turbulent transport compared to the discrete-in-time approach. In the prevailing paradigm for plasma turbulence, a unique, stationary turbulent state is associated to given equilibrium plasma parameters. This thesis reports the first instance of bistable turbulence in a fusion plasma with rotational shear. Two distinct states, obtained with identical equilibrium parameters in first- principle gyrokinetic simulations, have turbulent fluxes of particles, momentum and energy that differ by an order of magnitude – with the low-transport state agreeing with experimental observations. The occurrence of the two states is regulated by the competition between the externally imposed, mean rotational flow shear and “zonal” flows generated by the plasma. With small turbulent amplitudes, zonal flows have little impact on transport, and the mean shear causes turbulence to saturate in a low-transport state. With larger amplitudes, the zonal shear can substantially oppose the effect of the mean shear, allowing the system to sustain a high-transport state. This poses a new challenge for research that, so far, has assumed a uniquely defined turbulent state.

Keywords: physics
plasma
fusion
gyrokinetics
turbulence
Advisor: Barnes, M