VictorJuiz/thesis huggingface dataset:
Synthesizing the quality of study methodology and evidence to support guidelines for optimal treatment of falciparum malaria in pregnancy

Pregnant women are particularly susceptible to malaria, which is the leading cause of mortality and morbidity of the mother and fetus in the tropics. The current World Health Organization (WHO) recommended study design for assessing antimalarial efficacy excludes pregnant women, which has resulted in fewer studies on treatment efficacy and greater variability of study designs in pregnant women. Based on limited evidence, WHO has recommended quinine (with clindamycin, if available) for first-trimester and artemisinin-based combination therapy (ACT) for second- and third-trimester women since 2015. The data on the safety of artemisinin-derivatives in the first trimester have been collected, mostly from inadvertent treatments, over two decades, and form reassuring evidence of safety, strikingly different to animal-based reproductive health studies. This thesis aims to summarize the evidence on the efficacy of antimalarials for uncomplicated falciparum malaria in pregnancy and to improve future research in tropical infectious diseases in pregnancy.
Secondary data from prospective studies that assessed antimalarial efficacy by polymerase chain reaction were sought. Individual patient data of 4968 pregnant women (92% of all published work) from 19 studies in ten countries were pooled in a standardized format and analysed. These confirmed that quinine is less effective and less tolerable than ACTs. Quinine is also less suitable for elimination because of a higher risk of gametocyte development. Among ACTs, artemether-lumefantrine (AL) showed a slightly lower efficacy. In the second and third trimesters, the risks of congenital abnormality, miscarriage, stillbirth, preterm birth and small-for-gestational-age were similar among the four major ACTs (namely, AL, artesunate-amodiaquine, artesunate-mefloquine and dihydroartemisinin-piperaquine).
Study designs need to be tailored for pregnant women. It is probably necessary to follow up pregnant women for longer to assess efficacy accurately, but proof can only be obtained by including them alongside non-pregnant reproductive-age women. To assess pregnancy outcomes, precise and reliable estimates of gestational age and longitudinal recording of repetitive malaria episodes through to delivery are essential.
Quinine monotherapy should be replaced with ACTs for treating uncomplicated Plasmodium falciparum malaria in pregnant women. For AL, the most commonly used compound, dose optimization studies are needed. Investigations to find safe and effective drugs for pregnant women should be continued as every effort to prevent and reduce recurrence contributes to health of the mother and fetus.

Keywords: Plasmodium falciparum
pregnancy
artemisinin
quinine
malaria
treatment
infectious diseases
epidemiology
tropical medicine
Advisor: Guérin, P
McGready, R
Testing gravity with black holes

In this thesis, I study the ways in which modified theories of gravity might be tested for using black holes. In particular, I focus on ways in which the gravitational waves emitted during the ‘ringdown’ of a perturbed black hole may be affected.
I will develop and demonstrate the use of a framework for analysing the evolution of perturbations in arbitrary modified gravity theories in both cosmological and black hole backgrounds. I will use this to show that the characteristic Quasi-normal mode (QNM) spectrum of frequencies for the gravitational waves emitted from a perturbed black hole may be altered even in the case that the background black hole is identical to a general relativistic black hole. This is purely due to the presence, and coupling to, additional gravitational degrees of freedom.
I will also explore the landscape of hairy black hole solutions in the wake of the multi- messenger observation of GW/GRB170817, and show that it is increasingly difficult to endow a black hole with scalar hair in modified gravity given the constraint that gravita- tional waves must propagate at the speed of light.
In addition, black hole perturbations in General Relativity are analysed, with analytic expressions for QNM frequencies calculated for scalar, vector, and gravitational perturba- tions to a slowly rotating Kerr-(Anti-)de Sitter black hole.
Finally, I will examine the specific case of black hole perturbations in Horndeski the- ory, demonstrating the qualitative difference in gravitational wave emission from a per- turbed black hole in General Relativity and in Horndeski gravity. I will also forecast the detectability of such a modified gravitational wave signal, and estimate what constraints one might be able to place on fundamental parameters of Horndeski gravity through gravi- tational wave observations.

Keywords: Ringdown
Black Holes
Gravity
Advisor: Ferreira, P
Exploring the use of routine data for recruitment and follow-up in large randomised trials

Timely recruitment and comprehensive follow-up of patients are vital to the success of randomised controlled trials (RCTs) but both present issues. This thesis aims to investigate how routine data can be used for recruitment to clinical trials, whether there are any biases introduced by using routine data, and to determine whether routine data can be used as a follow-up method in clinical trials.
The literature on the use of routine data for recruitment and follow-up are explored in two systematic literature searches. Both reviews highlight that routine data can be used for recruitment and follow-up in RCTs. One finding is that these methodological aspects of RCTs, particularly when not pertaining to the results, are often not reported.
Using data from two large cardiovascular disease trials, the Heart Protection Study (HPS) and the Randomized EValuation of the Effects of Anacetrapib through Lipid-modification trial (REVEAL), that used electronic health records to recruit patients, the demographics of those entering the trial and declining to participate are investigated. A significant sex difference is observed, with females being less likely than males to progress through the recruitment pathway of both clinical trials. Attendance at follow-up visits and adherence to treatment were also significantly worse in females than in males. This disparity may leave studies underpowered for sex specific effects. These factors potentially limit the ability to establish the safety and efficacy of interventions in females and have the potential to have serious adverse public health consequences.
The use of routine data for follow-up is investigated by comparing the outcomes from HPS (non-fatal myocardial infarction, non-fatal stroke, revascularisation, and major vascular event) and the outcomes reported in Hospital Episode Statistics (HES) during the same time period. All of the trial outcomes were well recorded in the HES dataset, with no significant differences between males and females in their reporting of events. The use of routine data for follow-up in RCTs could reduce the frequency of study visits, which may aid recruitment.
Routine health records contain a wealth of information about patients that can be used to optimise both recruitment to trials and the follow-up of patients. The use of electronic health records (EHR) has the potential to provide more cost-effective and efficient methods for research.

Keywords: Clinical trial methodology
Population Health
Electronic health records
Advisor: Lay, M
Landray, M
Armitage, J
Collins, R
The polymedia movement of KONY 2012: humanitarianism and millennial activism in the digital age

This thesis seeks to understand the challenges and complexities of humanitarianism and youth activism in contemporary America by focusing on a ‘polymedia movement’ known as KONY 2012. KONY 2012 became the most viral video and humanitarian campaign to date when it was released by an American organisation called Invisible Children. KONY 2012 presents a uniquely powerful example of current trends in social relations and an instance of how people might be motivated to associate in a future that is shaped by social media. It is a phenomenon that, therefore, warrants the attention of anthropologists. This research integrates digital and traditional ethnographic methodologies and offers an academic contribution to an anthropological understanding of viral videos and polymedia movements. It considers the important roles of community, neo-colonialism, religion, celebrity and (social) media in relation to three key foci surrounding the movement: online activism, humanitarianism and millennial youth culture. The objective of the research is to identify the social and anthropological mechanisms underpinning the KONY 2012 phenomenon through investigative techniques including ethnography, so as to contribute to anthropological theory and knowledge and also to gain broader insight into the complicated, complex and multifarious social worlds we live in. The research found that the polymedia movement of KONY 2012 often reinforced the same practices of child-soldiering that it sought to eliminate, by inadvertently supporting a government that employed the same tactics. Furthermore, while the movement served a key role in the community and identity of American millennials, it was simultaneously plagued by corrupt government agendas both in Uganda and the United States, as well as the neo-colonialist mentalities of external groups, including religious organisations. KONY 2012 reveals the vast complexity of contemporary social movements, humanitarianism and online activism in the United States.

Advisor: Banks, M
Rape adjudication and prosecution in India: a reflection of female autonomy or masculine cultures?

The December 16, 2012 Delhi gang-rape case sparked a sorely-needed debate in India on the issues of consent in rape law, leading to the Justice Verma Committee report and the 2013 criminal amendment to rape law. This thesis undertakes a comprehensive analysis of Indian judicial decisions adjudicating rape, to ascertain (whether and) how underlying preconceptions and prejudices (continue to) percolate through sexual assault cases in a variety of settings (despite the 2013 amendment) and ultimately shape their outcome.
This thesis notes that the 2013 Amendments brought about some key reforms in the rape law, such as: an expansion in the definition of rape (beyond penile-vaginal intercourse); a new positive definition of ‘consent’ in section 375; and the addition of circumstances falling within category of ‘aggravated rape’ in section 376(2). This thesis argues that despite the sweeping changes introduced by the Parliament’s decisions, the statutory law still falls short of goals set by the Verma Committee report. There also appears to be legal gaps that exist in statutory law pertaining to previous sexual experience of the complainant and application of mens rea in rape law. Using direct evidence from the sample of cases, this thesis then presents the argument that the judicial discourse pertaining to rape reveals that statutory legal changes were not sufficiently powerful to dislodge deep-seated stereotypes amongst either the male or female judges. The complete silence on concepts such as bodily integrity and sexual autonomy, the lack of engagement with the new definition of consent, the absence of reference to the reversal of the burden of proof under section 114A in aggravated rape cases, the emphasis on factors like absence of resistance, and the dominance of stereotypes in the post-2013 law judgments indicate that there is a huge disconnect between the Parliament’s intention and the Judiciary’s implementation.

Keywords: India
Criminal law
Rape law
Advisor: Hoyano, L
Z-nucleic acids in virus-host interactions

One of the biggest threats faced by cells is infection. When a virus infects a cell, its nucleic acids can be recognised by cellular sensors, which activate potent antiviral innate immune responses, such as interferons and cell death. These initial responses are vital in preventing the spread of infection to surrounding cells. Critically, nucleic acid sensors must have mechanisms of recognising foreign, aberrant or mislocalised nucleic acids and distinguishing them from unperturbed cellular nucleic acids. Alternative conformations of nucleic acids may represent a molecular sign of virus infection that can be sensed. Double-stranded DNA and RNA can adopt different helical conformations, including the unusual Zconformation. The existence of proteins containing Z-binding domains (ZBDs) suggests Z-nucleic acids have important but so far poorly characterised biological functions. One such protein is Z-DNA binding protein-1 (ZBP1/DAI/DLM1). Using mouse cytomegalovirus as a model, we demonstrated that ZBP1 mediates virusinduced necroptotic cell death in a manner dependent on its two ZBDs. This suggests that the trigger for ZBP1 may be a Z-conformation nucleic acid. Knock-in mice, in which the ZBDs of ZBP1 are mutated, were more susceptible to virus infection. In addition to these mouse studies, we have demonstrated that ZBP1 also activates ZBD-dependent necroptosis in human cells and established and validated an assay for screening of small molecule or viral protein antagonists of ZBP1- mediated necroptosis in a human cell line.

Keywords: ZIKV
ZBP1
DAI
VZV
Nucleic acid sensing
Necroptosis
Pattern recognition receptors
MCMV
Advisor: Rehwinkel, J
Simmonds, P
Maelfait, J
The countryside of Florence and Lucca during the High Middle Ages (11th - 13th centuries). A study on land management and its change

This thesis examines the history of land management in the countryside of Florence and Lucca during the central medieval period (1000-1250). In particular, it analyses in depth the decades from c. 1180 to c. 1230, a phase that was marked by an overall transformation of estate-management forms, due to the political and economic context of that time. The thesis is structured in five chapters. Chapter 1 is divided into two main sections: the first one discusses the history of historiography, and stresses that the forms of land management in Tuscany during the central Middle Ages have been relatively less studied in comparison to the early and late Middle Ages; the second one outlines the political history of Lucca and Florence between the 11th and the 13th centuries. Chapter 2 sets out the two historical processes (indeed, the two main conceptual tools) that constitute the background to the rest of the thesis: first, it describes the early medieval manorial system (sistema curtense) in the countryside of Lucca and Florence; second, it examines the characteristics of the signorial mutation over the 11th and the 12th centuries, when local powers replaced the political authority of the marquises of Tuscia (the ancient name for Tuscany). Chapters 3 and 4 present a series of case-studies that are relevant to the history of land management in the Fiorentino and the Lucchesia. They show that a radical change was taking place from the 1180s onwards; in the Fiorentino corvée-work was abolished, whereas in the Lucchesia fixed rents in kind were increased substantially. Chapter 5 proposes an explanation for this process of change, which, moreover, can be linked to the development of sharecropping holdings (mezzadria poderale) around Florence in the late Middle Ages, and to the absence of a similar development around Lucca over the same period.

Advisor: Wickham, C
The values of freedom and the moral foundations of freedom-centred justice

What role should freedom play in a theory of justice? In this thesis I defend the view that freedom has non-specific value (i.e. that there is value in having freedom as such and not only in having certain specific valuable freedoms), and I examine the moral foundations of freedomcentred justice (i.e. of a theory of justice that is concerned with distributing freedom as such). The main contribution of this thesis consists in offering an in-depth examination of two distinct classes of reasons that justify attributing non-specific value to freedom: axiological reasons that appeal to the good, and deontic reasons that appeal to the right.
Good-based accounts include the views that interpret the value of freedom in person-affecting terms – especially, the Benefit View, which attributes personal value to freedom – as well as views that claim that it is impersonally good that persons have freedom. I focus then on examining the different senses in which people benefit from having freedom (Benefit View), since freedom is objectively valuable for the achievement of wellbeing, agency, autonomy, and human excellence. I also put forward a critique of the perfectionist foundations of freedomcentred justice, and I examine whether the moral foundations of freedom-centred justice can appeal exclusively to the Benefit View, or whether freedom-centred justice must (also) appeal to deontic reasons.
I put forward a critique of moralised accounts of the value of freedom, and I defend a nonmoralised interpretation of the Status View – i.e. the view that interprets the value of freedom in deontic terms and that appeals to the value of refraining from interfering with people’s freedom in recognition of people’s moral status as agents. In particular, I argue that interference with people’s freedom is pro tanto disvaluable, including when it is directed at preventing people from performing severely wrong actions, if in ideal theory we take people’s lack of disposition to act immorally as parametric (i.e. if we assume full compliance). Finally, I argue that distinguishing between the Benefit View and the Status View has implications for the conceptual analysis of freedom, shedding light on debates concerning the relations between freedom and ability: freedom is an interpretative concept and different ways of valuing freedom inform, and can actually determine, what freedom is (i.e. the definition of freedom).

Keywords: Freedom
Value Theory
Conceptual Analysis
Liberalism
Advisor: Stemplowska, Z
Miller, D
Chromium stable isotope variations in the early solar system and deep Earth

This study uses high precision chromium (Cr) isotope measurements to provide insights into the composition of the mantle, and constraints on the material from which Earth accreted. This involved achieving a deeper understanding of Cr isotope fractionation, facilitating the determination of a more precise δ53Cr for the bulk silicate Earth (BSE). This in turn leads to a comparison with different classes of chondrites as representatives of distinct types of disk material.
The δ53Cr composition of the mantle is unaffected by partial melting, but is perturbed by different metasomatic processes, which has created a δ53Cr heterogeneous mantle. An accurate δ53Cr BSE value cannot be acquired using mantle peridotites due to the widespread metasomatic variations they record. An alternative method to calculate the δ53Cr BSE composition is to use komatiites, as they sample a large volume of the mantle. The δ53Cr of komatiites varies during fractional crystallisation, which must be considered when calculating the initial composition. Different methods were used to determine the initial composition of the komatiite liquid. A weighted average is best able to account for the variations to the δ53Cr during crystallisation, and produces a well-constrained BSE composition, -0.12 ± 0.03 ‰.
Enstatite chondrites are meteorites that may have made up a significant proportion of the material that formed the Earth. The δ53Cr isotopic composition of the enstatite chondrites are within error of the BSE, with the closest match provided by EH chondrites.

Advisor: Halliday, A
Bonnand, P
An investigation of the association between sleep disturbance and mood instability

Mood instability (MI) and sleep disturbance (SD) are common in the general population, especially among persons with mental illness. Independently, MI and SD are associated with a range of poor health outcomes; however, there exists little evidence about their relationship. Using a series of six studies, this thesis investigated the relationship between MI and SD as transdiagnostic features on a shared pathway to ill health.
A systematic review of the prevalence of MI in the general population showed few and highly heterogeneous reports available within the literature. The results of the review highlight pervasive challenges underlying the study of MI, particularly the absence of consistent definitions and thoroughly validated measurement tools.
To investigate the epidemiological association between MI and SD, studies two and three examined data from a nationally representative survey of English adult household residents. Study three revealed that both MI and SD are common and closely linked within the population and associated with increased occurrence of suicidal ideation and behaviour. Study four showed that MI and SD are strongly and significantly associated with a wide range of poor mental and physical health and social outcomes such as difficulties with activities of daily living, socioeconomic indicators, and diagnosed health conditions.
In study four, prospective data on MI and SD from electronic health records from secondary mental health care showed that MI and SD are associated with significantly higher rates of mental health services use, hospitalisation, and prescribed medication.
Finally, an attempt to disentangle the directionality between MI and SD found strong cross-sectional evidence, but weak evidence of temporal trends between mood and sleep changes.
Taken together, the results of this thesis highlight existing and ongoing challenges to the study of highly temporal data on a large scale. However, the findings of this thesis provide essential knowledge for linking future epidemiological studies with high resolution examination of dynamic processes such as MI. Clinically, there is a critical need for increased recognition of MI and SD as modifiable risk factors of illness and related complications, rather than secondary symptoms. Earlier and effective intervention may help to reduce the burden associated with MI and SD, and mental illness.

Keywords: sleep problems
Mood instability
Advisor: Geddes, J
Saunders, K
Testing and learning on distributional and set inputs

As machine learning gains significant attention in many disciplines and research communities, the variety of data structures has increased, with examples including distributions and sets of observations. In this thesis, we consider sets and distributions as inputs for machine learning problems. In particular, we propose non-parametric tests, supervised learning, semi-supervised learning and metalearning methodologies on these objects. In each case, with careful consideration of the input structure, we construct models that are applicable to various real life tasks.
We begin by considering the problem of weakly supervised learning on aggregate outputs, where the labels are only available at a much coarser resolution than the level of inputs, such that a set of inputs corresponds to each output. Constructing a tractable and scalable framework of aggregated observation models using Gaussian processes, we apply it to the important problem of fine-scale spatial modelling of malaria incidences. In particular, it is demonstrated that the prediction of unobserved pixel-level malaria intensities is possible using finescale environmental covariates.
Utilising the same data structure, but with the interpretation that the set of samples is drawn from a distribution, we consider the problem of modelling distributions in the context of hyperparameter selection for supervised learning tasks. Through transfer of information from previously solved tasks using learnt representations of the training datasets, we construct a Gaussian process framework that jointly models all the meta-information available. In application to a range of regression and classification tasks, we demonstrate that we achieve faster convergence compared to the state-of-the-art baselines.

Keywords: Bayesian
Kernel methods
Advisor: Sejdinovic, D