VictorJuiz/thesis huggingface dataset:
Data integration and simulation of population immunity at the beginning of a pandemic

Accurate knowledge of population exposure at the outset of a pandemic has critical ramifications for preparedness plans for future epidemic waves. In this thesis, I developed a mechanistically informed statistical model to integrate multiple epidemiological datasets in different settings and in different population and to estimate key epidemiological parameters as well as population exposure using Bayesian inference.
First, I present a dynamic model to link together three key metrics for evaluating the progress of COVID-19 epidemic in England: seroprevalence, PR-PCR test positivity and death. While estimating the IgG antibody seroreversion rate and region-specific infection fatality ratios, I find that epidemic progression resulted in an increasing gap between measured serology prevalence levels and cumulative population exposure to the virus. Ultimately, this may mean that twice as many, or more, people have been exposed to the virus relative to the number of people who are seropositive by the end of 2020.
Moreover, I demonstrate that the model could reconstruct the first, unobserved, epidemic wave of COVID-19 in England from March 2020 to June 2020 as long as two or three serological measurements are given as inputs, with the second wave during the winter of 2020 validated by the estimates from the ONS Coronavirus Infection Survey. Comparing with the inferred exposure, I find that the UK official COVID-9 online dashboard reported COVID-19 cases only accounted for less than ten percent by the end of October 2020. I then generalise the model to account for the undocumented COVID-19-related mortality and sparse measurements of seroprevalence. I apply this in the context of Afghanistan COVID- 19 epidemic and find the population exposure in nine regions of Afghanistan were all higher than the seroprevalence survey suggested by July 2020.
Finally, I assess the impact of shielding among pregnant patients by comparing their exposure with the estimated exposure of the general population. To approach this, I develop a dynamic model to link RT-PCR and antibody testing results from patients who gave birth and then apply Bayesian inference to estimate transmission parameters and exposure among pregnant patients. I find that after considering the duration of each pregnancy pre-COVID onset and after, the impact of shielding on reducing the level of exposure among pregnant patients during early 2020 who gave birth in this New York City hospital were approximately 50%.

Keywords: pandemic preparedness
data integration
shielding
data-scarce scenarios
population exposure
COVID-19 pandemic
Advisor: White, L
Lythgoe, K
Stereoselective cyclisation cascades mediated by carbon electrophiles to access novel polycyclic scaffolds

The research outlined in this thesis describes the progress achieved in carbon electrophile-triggered cationic cyclisation cascades. The cation-initiated polyene cyclisation to form carbocyclic rings, as well as heterocyclisation to form novel lactones, has been explored. High levels of diastereoselectivity in setting up new stereocentres during the cyclisation were achieved. Furthermore, initial studies to control the absolute configuration of products were conducted. The results and all the experimental data are discussed in detail in the corresponding chapters.
Chapter 1 provides a literature overview of the current stereoselective polyene cyclisation and heterocyclisation methodologies. Different modes of initiating a cascade cyclisation are discussed. In addition, the role of HFIP solvent in facilitating cationic transformations, such as carbocation generation, is described.
Chapter 2 describes the development of a novel cation-triggered polyene cyclisation cascade. First, the formation of single ring systems is explored. The results from this part are then used to achieve the formation of multiple carbocyclic rings in a single step bearing a new exocyclic C-C bond. Finally, the developed methodology is applied for the synthesis of steroid-like compounds, including the formal synthesis of (±)-nor-estradiol.
Chapter 3 outlines the progress achieved in alkylative lactonisation via previously an unexplored 5/6-exo-trig cyclisation pathway. The synthesis of fused and spiro-lactones using HFIP-alcohol system is detailed, accompanied by control experiments and mechanistic studies aimed at elucidating the reaction mechanism.
Chapter 4 details the initial studies on enantioselective Ir-catalysed polyene cyclisation and heterocyclisation via asymmetric allylic substitution.
Chapter 5 provides the summary and major conclusions of the conducted research. Furthermore, potential future work is discussed.
Chapter 6 lists all the experimental procedures and analytical data for all the compounds discussed in this work.

Keywords: polyene cyclisation
lactonisation
enantioselective catalysis
organic chemistry
carbocations
Advisor: Donohoe, T
Unraveling the Weddell Gyre: exploring its dynamics and influence on Southern Ocean ventilation

The Southern Ocean is an area of great importance when considering anthropogenic climate change but also an area of great uncertainty. Between climate projections, the Southern Ocean is where one finds the most disagreement in both heat and carbon uptake. The Weddell Gyre is the largest coherent circulation south of the Antarctic Circumpolar Current (ACC) and mediates the transport of water to and from the Antarctic shelf. Here we use a diverse range of methods to study the dynamics of the Weddell Gyre and its role in Southern Ocean ventilation.
An idealized model of the Weddell Gyre and the ACC is used to investigate the gyre’s sensitivity to mesoscale eddies. The gyre is particularly strong at eddy-permitting resolutions (45 Sv with a noisy bathymetry) and weakest at eddy-parameterized resolutions (12 Sv). Simulations with partially resolved eddies have the largest horizontal density gradients. The steep isopycnals intensify the gyre's thermal wind transport and fuel tall columns of eddy kinetic energy which excite the gyre circulation at the sea floor.
The vorticity budget of a realistic Weddell Gyre simulation is calculated to identify important forces for the circulation. The gyre’s vorticity budget is dominated by a spurious component of the Coriolis force which emerges from the C-grid geometry. We identify two topographic and two non-topographic components of the spurious force. The topographic components can be mitigated by using a terrain-following coordinate and all components vanish when the B-grid is adopted.
Backwards-in-time trajectories are used to identify spatial and temporal patterns of Southern Ocean ventilation on a thirty-year timescale. Practically all ventilation occurs between August and November. Sites of deep convection are responsible for 60% of open ocean ventilation. Almost no ventilation occurs within the subpolar gyres but their western boundary currents are the primary export pathway for shelf-ventilated water.

Keywords: climate change
Weddell Gyre
oceanography
subpolary gyre
model discretization
ocean circulation
southern ocean
gyre
vorticity
ocean modelling
eddies
ocean ventilation
shelf processes
Weddell Sea
Advisor: Marshall, D
Bell, M
Writing a Trans History of HIV/AIDS in Britain, 1985-1996

There is currently no trans history of the HIV/AIDS epidemic in Britain, despite modern transgender people being considered an ‘at-risk’ group. This thesis represents a first attempt to construct this history, focusing on archives over oral histories to contend head-on with how this history has been systemically un-seen. Analysing British gay and transfeminine organisations in the 1980s and 1990s – namely, comparing the relationship between The London TV/TS Group and the Lesbian and Gay Switchboard - this thesis argues that the pathological gaze of ‘transsexuality’ through the panopticon of NHS Gender Clinics prohibited subjects from conceiving trans people as susceptible to HIV/AIDS. In the style of Jules Gill-Peterson, this thesis introduces the framework of ‘transsexual eugenics’: the roots of transsexual medicine lay in eugenic science, and I argue that this relationship with eugenicism enforced its patients to rescind all attachments to life beyond heteronormativity, and AIDS was conceived as the antithesis of normativity through popular associations with homosexuality and sex work. After Chapter One establishes the theoretical basis in postcolonial and transgender theory, Chapter Two expands on ‘transsexual eugenics’ through arguing the largest trans organisations during the AIDS epidemic were too intertwined with Gender Clinics to realise their internalisation of eugenic rhetoric, thus rendering AIDS unthinkable alongside a diagnosis of transsexuality. Chapter Three concludes by analysing the reciprocal relationship between the London TV/TS Group and Switchboard to conclude that the transmission of eugenicist Gender Clinic rhetoric from the Group into Switchboard prevented Switchboard from delivering AIDS sexual health information to trans callers. This thesis hopes to inspire historical interest in the British trans history of HIV/AIDS, as well as further critiques of mid-twentieth century transsexual medicine.

Keywords: gender identity clinics
transgender
britain
eugenics
HIV/AIDS
Lesbian and Gay Switchboard
Politics and imagination : Soviet children's culture and the space age, 1957-1964

As the first man-made satellite orbited the Earth in October 1957, radios worldwide transmitted its persistent signal. Sputnik’s pulsing beep was either the most exhilarating proof to date of man’s rapid technological development, or a haunting reminder that, in the bi-polar world, science and technology had become the yardstick by which ideological battles were won or lost. For some the incessant tone represented the triumph of Soviet socialism. For others, it meant a new and harrowing challenge to Western democracy and capitalism. Though these perspectives were, in fact, inseparable, each represented a quantitatively different world view in the ideologically contentious atmosphere of the Cold War. Regardless of where one stood in this polemic, Sputnik represented the first foray into a realm previously explored only in works and dreams of scientific and literary visionaries.
The emergence of the space age in the middle of the twentieth century had an enormous impact on virtually every sphere of international life. Sputnik was the ‘shot’ that set thousands of scientists, millions of rubles (and dollars), and a seemingly endless stream of propaganda in motion, from both East and West. The early years of the Soviet space program offer an interesting and important perspective on Soviet history precisely because of this massive mobilization of resources. No group, from the most exalted party apparatchik to the lowest kolkhoz worker (and such class distinctions were well entrenched and problematic for the Khrushchev regime, as chapter 3 will discuss) was immune from Sputnik’s influence. This paper seeks to explore the influence of this epoch-defining event on a group whose members were not defined primarily by class affiliation or profession but rather by age: Soviet children.
Continued in thesis ...

Keywords: astronautics
children
civilisation
culture
space age
civilization
Soviet Union
imagination
politics
An integrated inflammatory and metabolic profiling of stromal-epithelial cell interactions in colorectal cancer

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and ranks second as the leading cause of cancer deaths worldwide. Notably, it was predicted that a positive annual decline of 2 % in global incidence rates would eventually still lead to a rise in the projected burden of CRC. Therefore, it is pertinent to push the forefront of cancer treatments to reduce the predicted increase in the future CRC incidence and mortality burden.
Immunotherapy represents a paradigm shift in cancer treatment and has quickly established itself as a robust pillar of therapy for multiple cancers. However, immunotherapy has shown disparate results in the treatment of CRC, and its efficacy in the broader population of CRC patients remains limited. Particularly, no immune-checkpoint blockade targeting PD-L1 has yet to be approved for CRC. As such, more research is warranted to identify strategies to expand the benefits of immunotherapy to a wider CRC patient population.
To date, many studies have highlighted that PD-L1 expression level has a strong association with positive clinical response to anti-PD-L1 therapies. As such, we reasoned that one encumbering factor to the mixed clinical responses in CRC is the infrequent expression of PD-L1 in CRC cells. Using a range of in vitro culture techniques and multi omics approaches, we found that myeloid cells have a profound impact on CRC PD-L1 expression. Mechanistically, myeloid cells forced CRC cells to switch to oxidative phosphorylation (OXPHOS) as its default metabolic state. Here, we uncovered a direct link of OXPHOS regulating cellular protein III translation, which has not been reported previously. Along with this observation, we also discovered that glycolytic switch to OXPHOS in CRC cells lead to a downregulation of EGFR phosphorylation that reduces PD-L1 glycosylation and by extension its stability. Coupling together, this led to a significant suppression of CRC PD-L1. Furthermore, we found that polarization of monocytes to macrophages further downregulated PD-L1, which strongly suggests a long-term PD-L1 suppression by tumour-associated macrophages, as observed clinically. Lastly, we saw a reversal of PD-L1 suppression when transition to OXPHOS was inhibited pharmacologically. Concomitantly, this pharmacological approach also suggests a change in macrophage polarization trajectory towards an anti-tumorigenic phenotype. Collectively, our findings open up a potential druggable avenue to reinvigorate PD-L1 level in CRC via OXPHOS inhibition and explore the possibility of synergizing with PD-L1 blockade.

Advisor: Kerr, D
James, W
Shijie, C
On robustness for natural language processing

As a discipline, machine learning has contributed to significant breakthroughs in Natural Language Processing (NLP), aiming to design algorithms to manipulate text and produce insights, such as classification and summarization, comparable to those of humans. Natural language poses challenges that reflect peculiarities of human intelligence, such as grasping the meaning of a sentence or preserving long-term relationships between words that possibly appear distant from each other.
A considerable body of recent literature provides evidence that NLP models behave inconsistently on slight manipulations of a text, as in the case of word substitution. Differently from computer vision (CV), where a pixel manipulation produces a (possibly not natural) image, NLP algorithms rely on text representations in the form of embedded vectors, where the linguistic constituents (i.e., words, phrases, sentences) are transformed into multi-dimensional vectors of real-valued numbers, marking a clear separation between human and machine representation.
In this thesis, we investigate guarantees and the formal explainability of NLP models through the lens of adversarial robustness. We review the applicability of adversarial robustness, as defined in CV, as the region of maximal safety of a neural network (NN) decision against discrete and continuous perturbations. We develop an evaluation framework that certifies adversarial robustness for different models, and we analyze how the validity of such certificates vanishes in settings that grow in complexity. This investigation is a prelude to novel definitions of robustness that are aligned with linguistics, aiming to assess a model's syntactic and semantic capabilities.
With semantic robustness, we introduce a framework to test a model against linguistic phenomena. In contrast, syntax robustness aims to falsify the hypothesis that NLP models embed high-order linguistic structures such as syntactic trees. Extensive experimentation on various architectures and benchmarks validates the proposed concepts and sheds light on how brittle these architectures are against slight linguistic variations, against which humans are exceptionally robust.
We finally investigate the role of robustness as a property to explain neural networks: we propose the notion of optimal robust explanation (ORE) as the robust and optimal portion of an input text that is nevertheless sufficient to imply a model's decision. We implement and test this notion of explanations on various neural networks and datasets to reveal the explanatory landscape of NLP models through the lens of robustness.
All the software and tools of this thesis have been released under permissive, open-source licenses to satisfy reproducibility requirements and encourage other researchers to develop tools to assess and improve the robustness of NLP models against edge cases and linguistic phenomena, which by their nature constitute a non-negligible part of the spectrum of human language.

Keywords: robustness
linguistics
NLP
Advisor: Kwiatkowska, M
A realist perspective on the use of research evidence in health policymaking

The achievement of “evidence-informed” policy is an aspiration espoused by policymakers, academics and citizens alike, but governments have faced considerable challenges in pursuit of this ideal. The methodological orientation known as scientific realism, in which outcome patterns in the social world are understood as manifestations of the operation of social mechanisms in specific conducive contexts, is increasingly popular in the social sciences, including within public health and social policy. Yet, little research to date has examined evidence-informed health policymaking through a realist lens. This thesis addresses this gap.
The purpose of this thesis is to explore the usefulness and explanatory value of realist approaches for the study of the use of evidence by health policymakers, and the influence of complex interventions designed to institutionalize the systematic application of evidence to health policymaking. The thesis presents two qualitative syntheses and a primary case study in pursuit of this aim.
Following a survey of relevant literature (Chapter 1) and a discussion of methodological foundations (Chapter 2), a comprehensive systematic review of qualitative research on evidence-informed health policymaking is summarized (Chapter 3). The latter forms the basis for the subsequent two chapters, a thematic synthesis on the factors affecting evidence use by health policymakers (Chapter 4) and a realist synthesis on the institutionalization of evidence-informed policymaking (Chapter 5). The thesis then pivots from synthesized secondary evidence to original primary research. A qualitative realist case study on the knowledge transfer work of the West African Health Organization (WAHO) is presented (Chapter 6), culminating in the proposal of a realist program theory setting out explanations for how and under what conditions their flagship program – WAHO’s Knowledge Transfer Platform – influences the use of evidence in national health policymaking in West Africa. The thesis closes with a pair of essays that provide lessons, interpretations and critical reflections, both methodological (Chapter 7) and practical (Chapter 8).

Keywords: evidence-informed policymaking
realist methods
health policy
The role of adenosine in remote ischaemic conditioning

Strategies to reduce infarct size in ischaemia-reperfusion (IR) syndromes such as acute myocardial infarction are of high clinical and scientific interest. Remote ischaemic preconditioning (rIPC) is one such strategy but its mechanisms remain incompletely understood. Multiple lines of evidence from animal studies suggest that the endogenous purine nucleoside adenosine is a key mediator of preconditioning pathways but no evidence exists as to adenosine’s role in the more complex physiology of humans. The work in this thesis aims to elucidate the role of endogenous adenosine in the physiological phenomenon of rIPC and to examine the role of exogenous adenosine in triggering preconditioning-like states.
In a randomised, placebo controlled study using healthy volunteers and the human forearm model of ischaemia-reperfusion injury, I demonstrate that delivery of the adenosine receptor antagonist caffeine, prior to the initiation of a rIPC stimulus abrogates the protective effect of rIPC on IR. By then selectively infusing caffeine to achieve high local but low systemic concentrations, I also demonstrate that adenosine receptor activation is important in the ‘trigger’ phase of rIPC rather than in the ‘effector’ phase and that blockade of the trigger phase effectively inhibits the release of a circulating humoral protective factor. These studies provide evidence of the crucial role of adenosine receptor activation in human rIPC, demonstrating their sites of action and illuminating their potential mechanism of action.
To study whether exogenously delivered adenosine can recapitulate preconditioning-like states, in initial studies in a large mammal model of acute myocardial infarction, I demonstrate that adenosine, given after the onset of ischaemia, but prior to reperfusion, significantly reduces myocardial infarct size. In a subsequent study, translating these findings to humans with coronary disease, I demonstrate that the delivery of adenosine in a range of concentrations is able to illicit the release of a circulating preconditioning factor which is transferrable across species and can reduce infarct size in a murine model of myocardial IR.

Keywords: adenosine
cardioprotection
ischaemic conditioning
Advisor: Kharbanda, R
The condition of exile: Ghanaian exile networks and competing nationalisms, 1957-1993


This thesis provides an original analysis of the role of exile as an integral but neglected part of the historical and political landscape of post-independence Ghana. The prevalence of the nation-state as an analytical framework has led to the exclusion of exiles and other mobile individuals from conventional historical narratives, despite the significant impact which such transnational activists have had on the political development of Africa in general and Ghana in particular.
The thesis demonstrates that, through the creation of mobile networks of dissent, repeated waves of exiles affected and reshaped Ghanaian domestic politics, constituting a material challenge not only for the Ghanaian government itself, but also the governments of the countries they resided in. Exiles functioned as an externalised opposition, beyond successive governments’ coercive reach, disrupting state security and troubling key diplomatic relationships. Being beyond Ghana’s border did not prevent exiles from remaining active participants in Ghana’s development. Despite their externality, many ideationally and emotionally never left home.
Archival sources from across Ghana, the US, and the UK, alongside interviews, have been employed to explore how exiles remained entwined with the politics of their nation of origin. Regardless of geographical distance from Ghana, the global space of exile provided an important venue for contestation of the nation. This thesis combines multiple approaches, embracing not only the insights of global and African history, but also combining political realism with the affective turn. This derives from this thesis’ contention that the study of exile and its political impact is inseparable from its social and emotional dynamics. Emotion was central to how exiles perceived themselves in relation to their political aims and to Ghana as their home. Familial, social, and political ties defined these networks of resistance, ensuring their political impact spanned local, regional, and global spaces in unpredictable and entangled ways.

Keywords: military governments
Kwame Nkrumah
exile
coup d'états
migration
Africa
human rights
diaspora
Jerry Rawlings
Ghana
Advisor: Larmer, M