VictorJuiz/thesis huggingface dataset:
Improving the quantification of cerebral haemodynamics using optimally sampled arterial spin labelling MRI
Keywords: kinetic modelling
optimal sampling strategy
perfusion MRI
arterial spin labelling

Arterial spin labelling (ASL) is a non-invasive magnetic resonance imaging (MRI) technique that utilises arterial blood water as an endogenous tracer to measure cerebral blood flow (CBF). While the ASL white paper recommends the clinical use of a single post-labelling delay (PLD) pseudo-continuous ASL (pCASL) method to robustly quantify CBF, there has been a growing body of research on multi-delay ASL which provides the ability to estimate for parameters other than CBF.
A framework applying optimal sampling strategy (OSS) to multi-PLD pCASL sequences has been developed to obtain optimised protocols by minimising the estimation uncertainty on both CBF and arterial transit time (ATT) or CBF only. Although this framework is flexible for designing ASL protocols with a variable number of target parameters, it adopted an idealised kinetic model and used a narrow range of prior values in the optimisation, rendering the optimised protocols susceptible to various sources of error during estimation.
This thesis seeks to systematically investigate the estimation sensitivity of existing optimised protocols to a number of physiological effects that are not accounted for in the idealised model. Additionally, it aims to extend the current framework and develop novel protocols optimised for both delay and echo times to improve the estimation of blood-brain barrier (BBB) water exchange.
Firstly, four pCASL protocols were examined for CBF and ATT estimation performance with the effects of flow dispersion, macrovascular signal contamination (MVC), and prolonged ATT. It was found that the protocol optimised for CBF estimation had the lowest CBF sensitivity to MVC, and extended kinetic models were beneficial to control for the presence of these effects. Results from simulation were validated using a previously acquired in vivo dataset.
Next, parameter sensitivity to MVC were evaluated for a comprehensive set of protocols optimised for CBF estimation. A wide range of tissue and macrovascular transit time ground truths was considered, and different assumptions regarding the relationship between the two transit times were compared and discussed. The resulting sensitivity maps further illustrated the benefit of adding an extra compartment in the analysis to account for MVC and could be used for data interpretation.
Finally, the OSS framework was extended to enable the combined optimisation of PLD and TE in multi-TE pCASL to measure water exchange time, Texch, across the BBB. Protocols were optimised with different optimality criteria under two multi-TE schemes and evaluated in terms of their theoretical estimation root-mean-square errors (RMSEs) using simulation. While the optimised protocols resulted in lower RMSEs of corresponding parameter estimation, reliably detecting a pathological level of Texch change in an individual using the optimised protocols within five minutes remains challenging.
Anatomically informed Bayesian inference for physiological imaging
Keywords: arterial spin labelling
perfusion
surface
physiological imaging
variational bayes

Anatomy interacts with all aspects of physiological imaging. Notably, volumetric techniques of limited spatial resolution struggle to image complex anatomies such as the cerebral cortex. One consequence of this is the partial volume effect, which introduces bias or confound into parameter measurements derived from such images. Fundamentally, the effect arises because the manner of image acquisition and analysis is not well-suited to the anatomy in question. Correction for partial volume effects is generally regarded as an optional post-processing step without a commonly agreed-upon strategy and it does not address the root cause of the problem.
Recently, surface-based methods have been shown to offer substantial advantages for the study of the cortex. The benefits follow from the fact that a surface representation is more appropriate for the anatomy of the cortex, namely, a thin and highly folded sheet that forms a topological sphere. Thus far, little work has investigated perfusion measurement in the cortex via arterial spin labelling in an explicitly surface-based manner, though such measurements could improve the understanding of brain function and disease.
This work represents the convergence of these two themes of partial volume effects and surface-based analysis. The major contribution is a framework for performing parameter estimation in a simultaneous surface-aware and volumetric manner, i.e., in the spaces that are most appropriate for the different anatomies present within the brain. The motivation for doing so is to realise the benefits of surface-based analysis for perfusion measurement in the cortex via arterial spin labelling, without negatively impacting measurement in the subcortex. As a consequence of the combined surface and volumetric approach, however, a new treatment of partial volume effects is obtained. Rather than considering these effects as a secondary problem that can be mitigated via post-processing, the entire approach is in fact built around them. By incorporating the anatomy that causes PVE directly into the generative model that is fit to the data, correction becomes an intrinsic feature of the estimation framework and not an afterthought.
Modulation of basal ganglia local field potentials by deep brain stimulation in Parkinson's disease and dystonia
Keywords: Parkinson's disease
local field potentails
feedback markers
deep brain stimulation

Subthalamic (STN) deep brain stimulation (DBS) is an effective treatment option in advanced Parkinson’s disease, however, its underlying mechanism remains largely speculative. Continuous DBS may come with side effects such as speech impairment, paraesthesia and mood changes, which necessitates research into adaptive DBS. Adaptive DBS requires feedback signals reflecting pathological activity to guide stimulation. Previous studies have focused on beta oscillations in the STN as a potential biomarker for parkinsonian symptoms and beta power suppression has been suggested as a potential action mechanism of DBS. In this thesis, we sought to investigate mechanisms underlying STN stimulation beyond beta power suppression and studied other potential feedback markers to improve current frameworks of adaptive DBS.
In the first part, we performed local field potential (LFP) recordings from Parkinson’s disease patients and studied evoked and induced changes with DBS. DBS-evoked resonant neural activity (ERNA) consists of a high-frequency, high-amplitude activity focal to dorsolateral STN that has fast and slow components. Furthermore, the ERNA is highly adjustable and varies with different DBS frequencies, intensities, medication states and stimulation modes. DBS also induced instantaneous power suppression in the beta and gamma frequency range and de-novo finely-tuned gamma (FTG) oscillations that are modulated during and after DBS.
In the second part, we demonstrate in rodent data that aperiodic exponents of subthalamic LFPs reflect excitatory and inhibitory input to STN and report higher aperiodic exponents ON levodopa and stimulation, in keeping with more inhibition. Subsequently, we found aperiodic exponent changes with levodopa and DBS in Parkinson’s disease patients, consistent with more inhibition of STN when symptoms are alleviated.
In the third part, we recorded subthalamic and thalamic LFPs from cervical dystonia patients and found that neither ERNA, FTG, power suppression or aperiodic exponent changes with DBS are specific to Parkinson’s disease.
Overall, this thesis extends the knowledge on existing feedback signals for adaptive DBS and supports the inactivation hypothesis of subthalamic DBS.
Vaccine and assay development for nairoviral diseases
Keywords: Crimean congo haemorrhagic fever
emerging diseases
assay
disease
epidemic
vaccine
Nairobi sheep disease
pandemic
nairovirus

Emerging zoonotic diseases present a significant risk to global public health, as evidenced by the ongoing COVID-19 pandemic. Nairoviruses are a genus of viruses, which include Crimean Congo Haemorrhagic Fever Virus (CCHFV) and Nairobi Sheep Disease Virus (NSDV), and present a significant risk of epidemics in humans and animals. As such there is an urgent need to develop effective therapeutics and prophylactics to protect humans and livestock from nairovirus mediated infection and disease. Vaccines are a highly effective healthcare intervention, and ChAdOx vaccine platforms have been used extensively to develop vaccines against emerging diseases, including the ChAdOx1-nCoV19/AZD1222 vaccine. This thesis aims to characterise the development of ChAdOx vectored vaccines against a range of nairoviral antigens, and determine if nairoviral vaccines in ChAdOx vectors are immunogenic following vaccination in mice. As part of this thesis, new pseudotyping assays using CCHFV and NSDV glycoproteins were developed to test neutralising antibody responses induced following vaccination. This thesis demonstrated that CCHFV GPC (GlycoProtein Precursor), Gn, Gc, and NP (Nucleoprotein) antigens were all immunogenic, inducing cellular and humoral responses, and that ChAdOx vectored CCHFV GPC vaccination could induce neutralising antibodies. Further the immunogenicity of NSDV GPC, Gc, and NP antigens in ChAdOx1 vectors was demonstrated following vaccination. Development of multivalent ChAdOx1 CCHFV vaccines showed that a single vaccination could induce broad cellular and humoral immune responses. Anti-vector neutralisation responses induced by vaccination were also assayed in the ChAdOx1-nCoV19 vaccine clinical trial at the University of Oxford. The work in this thesis determined that no correlations were measured between anti-ChAdOx1 neutralisation titres and anti-SARS-CoV-2 spike immune responses following vaccination with ChAdOx1-nCoV19/AZD1222. Overall, this thesis highlights the development of immunogenic vaccines against the emerging pathogens CCHFV and NSDV, which will be crucial to managing future epidemics.
Structural foundations for probabilistic programming languages
Keywords: denotational semantics
categorical probability
programming languages
probabilistic programming
category theory

Probability theory and statistics are fundamental disciplines in a data-driven world. Synthetic probability theory is a general, axiomatic formalism to describe their underlying structures and methods in a elegant and high-level way, abstracting away from the mathematical foundations such as measure theory. We showcase the value of synthetic probabilistic reasoning to computer science by presenting a novel, synthetic analysis of three situations: the Beta-Bernoulli process, exact conditioning on continuous random variables and an investigation into the relationship of random higher-order functions and fresh name generation.
The synthetic approach to probability has merit not only by matching statistical practice and achieving greater conceptual clarity, but it also lets us transfer and generalize probabilistic ideas and language to other domains: A wide range of computational phenomena admit a probabilistic analysis, such as nondeterminism, generativity (e.g. name generation), unification, exchangeable random primitives and local state. This perspective is particularly useful if we wish to compare or combine those effects with actual probability: We develop a purely stochastic model of name generation (gensym) which is not only a tight semantic fit, but also uncovers striking parallels to the theory of random functions.
Probabilistic programming is an emergent flavor of Bayesian machine learning where complex statistical models are expressed through code. We argue that probabilistic programming and synthetic probability theory are two sides of the same coin. Not only do they share a similar goal, namely to act as an accessible, high-level interface to statistics, but synthetic probability theories are also the natural semantic domains for probabilistic programs. Conversely, every probabilistic language defines its own internal theory of probability. This is a probabilistic version of the Curry-Howard correspondence: Statistical models are programs. This opens up the analysis and optimization of statistical inference procedures to tools from programming language theory.
Much as category theory has served as a unifying model for logic and programming, we argue that probabilistic programming languages arise precisely as the internal languages of categorical probability theories. Our methods and examples draw from diverse areas of computer science and mathematics such as rewriting theory, logical relations, linear and universal algebra, categorical logic, measure theory and descriptive set theory.
Lived experiences of arsenic-related psychosocial distress in rural Bangladesh
Keywords: psychosocial distress
health
water quality
arsenic

Arsenic occurs naturally in the groundwater across much of Bangladesh, with millions exposed through drinking water. It has wide-ranging health effects, including skin lesions, cancers, heart disease, and cognitive impairment. There is also emergent but limited literature on its effects on psychosocial well-being. This paper advances the understanding of the relationship between arsenic exposure and psychosocial distress. An exploratory qualitative study was undertaken, where interviews were conducted with 23 members of an affected community in a village in southwestern Bangladesh. Results show that arsenic exposure is linked both directly and through mediated pathways to psychosocial distress. There are significant impacts on the participants’ lives, including inability to access safe water, lack of agency, chronic pain and discomfort, difficulty performing everyday tasks, lost productive time, issues of marriageability, among others – all of which contributed to psychosocial distress, both individually and compounded together. The findings indicate a need for more comprehensive understanding of arsenicosis when designing safe water interventions.
Ancestral halls and ‘modern temples’: museums in postcolonial Hong Kong
Keywords: museum-mindedness
ancestral hall
Hong Kong
museum anthropology
history museum
school museum
identity
amateur museum
museum studies
museology
heritage
independent museum
post-colonialism

In this thesis, I examine how the meanings and roles of museums, as a worldwide cultural phenomenon that has been initiated in Europe, are adapted and transformed according to local contexts beyond Europe. My ethnographic research explores the specific context of post-colonial Hong Kong and examines the rise of non-government museums. I argue that this phenomenon is the result of nostalgia, rising historical and cultural consciousness, increasing ‘museum-mindedness’ and the continuing identity dilemma experienced by residents, both young and old, of postcolonial Hong Kong. I have critically analysed five types of museum-like institutions in Hong Kong, namely: ancestral halls, governmental, independent, amateur, and school history museums. Investigating recent developments of museums in Hong Kong through the lens of Chinese ancestral halls, I argue that ancestral halls are, in effect, ‘precursory museums’ for those that have been created more recently. Enabled by objects, spatial experience and social interactions, Chinese ancestral halls and contemporary Hong Kong museums both aim to preserve and transmit cultural knowledge and, in the process, facilitate identity construction. Set up by all kinds of actors, ranging from independent trusts to individual amateurs, non-government museums in Hong Kong are diverse in their forms but united by the same aim and function: to preserve and interpret local heritage in their own ways and according to indigenous criteria.
In a broader sense, I suggest that the non-government museums represent different points in a continuous spectrum which at one end is influenced by an indigenous museological model associated with Chinese ancestral halls, and, at the other end, by government museums, which still uphold the values of ‘western’ museum professionalism. I argue that the values and principles upheld by those who have created and curated ancestral halls are still influencing current museums in the postcolonial era, because the museums have inherited the traditional, social and historical functions of ancestral halls in Hong Kong as a channel for the Hong Kong public to ‘retrace their roots’. Non-governmental museums in Hong Kong can also be potential sites of rejection of the official histories and representations constructed by the Beijing-influenced postcolonial Hong Kong government. They are therefore a manifestation of the postcolonial condition and a cultural arena in which Hong Kong residents could construct history, interpret culture, and shape identity.
Immigration and discrimination
Keywords: discrimination
migration

This thesis examines discrimination in immigration policy. It consists of two parts. The first part examines the normative significance of discrimination in the history of immigration policy. I argue that descendants of those who have been excluded by race or ethnicity have a right to immigrate to the state in question as reparation. This argument is based on one popular approach to justifying reparations for historical injustice: the counterfactual approach.
For much of the thesis, however, I examine discrimination in present-day immigration policy. This is the second part of the thesis. I put forward a pluralist account of discrimination in immigration policy. This, I argue, allows us to more fully capture discrimination in immigration policy than the monist account of discrimination that is implicitly adopted in the philosophical literature on migration. I develop this pluralist account of discrimination by examining three significant immigrant selection policies of countries in the Global North: selection by skill, selection by age, and selection by nationality.
I show that discrimination in immigration policy can be wrong for three reasons: if it fails to select by merit, if it demeans would-be immigrants, and if the selection unfairly disadvantages certain groups of people. I consider one possible solution to this discrimination in immigration policy: a lottery that selects immigrants. I argue that while lotteries are non-discriminatory, they are nevertheless unappealing for reasons that do not have to do with discrimination. Thus, non-discrimination cannot be the only standard by which we judge immigration policy. I end by considering what this entrenched discrimination means for immigration policy at large.
The totality of the thinkable
Keywords: epistemology
ens realissimum
theology
Kant

This thesis presents four chapters that address the theological and epistemological views of Immanuel Kant. Although each of the four chapters addresses a discrete problem, the chapters are united in their focus on the idea of the ‘totality of the thinkable’ and the related idea of a totality of possible concepts. In particular, this thesis explores the ways in which the totality of the thinkable is implicated in Kant’s criticisms of his German rationalist predecessors.
Chapter One explores Kant’s claim that the representation of God within transcendental theology has its origin in reason’s tendency to generate an idea of the totality of the thinkable (the omnitudo realitatis, in Kant’s terminology). It argues that existing interpretations of Kant’s claim cannot explain why reason generates the omnitudo realitatis. Chapter Two offers a novel account of the origin of the omnitudo realitatis in reason’s faulty effort to supply itself with a prototypical version of transcendental philosophy. Chapter Three explains how the omnitudo realitatis subsequently becomes the representation of God within transcendental theology, in the process addressing whether or not Kant endorsed a ‘Spinozistic’ conception of God. Chapter Four addresses the idea of God within Kant’s moral philosophy. It explains why Kant continually insists, in the Critical period, that his moral arguments are capable of justifying belief in a being with infinitely great properties.
The wrongness of image-based sexual abuse
Keywords: harmfulness
image-based sexual abuse
fair labelling
revenge pornography
personhood theory
non-concsensual intimate images
criminal law theory
criminalisation theory
intimate image abuse
relational personhood
wrongs
non-consensual pornography
wrongfulness

What is the nature of the wrongfulness of image-based sexual abuse (‘ibsa’)? That is the main question addressed in this thesis. The answer is found to depend on the understanding of personhood underpinning the interpretation of wrongs. It can be summarised as follows: on atomistic personhood, ibsa is a moderate infringement of autonomy, sexual integrity, privacy, and positive freedom of expression. There is limited theoretical scope for finding the absolute wrong of failing to minimally respect personhood. On relational personhood, ibsa is found to be much more seriously wrongful: it is a severe infringement of autonomy, sexual integrity, privacy, positive and negative freedom of expression, and can constitute a breach of trust. The absolute wrong of failing to minimally respect personhood can readily be found. On both approaches to personhood, ibsa is understood as part of the continuum of violence against women and, as such, as reinforcing and being reinforced by inequality.
A central claim of this thesis is that personhood is a fundamental element of interpreting wrongs against persons. Personhood is not typically appreciated as such, nor is wrongfulness usually at the focus of discussion when considering justified criminalisation. This thesis first sets out the justified scope of the criminal law in liberal democracies as demarcated by harmful, public wrongs. Wrongfulness is considered as an underexplored, core part of criminalisation theory. The thesis presents an original analysis of the significance of personhood in the context of interpreting wrongfulness and justifying criminalisation. That is followed by a discussion of atomistic and relational consent, and the role of (lack of) consent in finding wrongfulness. This thesis then uses the preceding analysis to interpret the wrongs of ibsa both on an atomistic and on a relational understanding of personhood, thus offering a two-part answer to the main question of this thesis. Finally, the thesis explores the implications of its findings on criminalisation theory and the criminalisation of ibsa. It defends the view that the law should take a relational understanding of personhood and that ibsa should be criminalised as a sexual offence.
Culture and capability: essays in behavioural economics
Keywords: agency
mental models
behavioural economics
development economics
narratives
stereotypes

How do mental models guide behaviour? Although a great deal of attention has been paid to mental models in psychology, relatively little is understood about how they inﬂuence incentivised decision-making or their relevance for policy. In this dissertation, I explore this question over the course of four papers. In the ﬁrst paper, I synthesize the literature on mental models and aim to situate it in standard decision theory. In paper two, I look at how people use mental models of social groups to determine strategies of action under incentivized conditions. In paper three, I look at how unemployed young people’s mental model of their agency within the world inﬂuences their decisions to search for work. In paper four, I look at how mental models of technology inﬂuence vaccine hesitancy.