VictorJuiz/thesis huggingface dataset:
Sensitivity and specificity of molecular methods for detecting markers of  antimalarial drug resistance in clinical  samples of Plasmodium falciparum: a systematic review

Background Each year infection with Plasmodium causes millions of clinical cases of malaria, and hundreds of thousands of deaths. Resistance to different antimalarial medications continues to develop and spread, threatening effective prophylaxis and treatment. Monitoring of resistance is required to inform health policy and preserve effective antimalarials; molecular methods can be used to determine likely parasite susceptibility. There is no consensus on the most accurate methods; large variation exists in practice. The goal of this systematic review was to identify the sensitivity and specificity of each molecular method for detecting antimalarial resistance markers.
Methods All diagnostic accuracy studies that examine at least two molecular methods for detecting selected markers of antimalarial resistance in blood samples from patients diagnosed with, or suspected of having malaria were included. MEDLINE, EMBASE, BIOSIS, and Science Citation Index were searched. Methodological quality was evaluated using QUADAS-2. Sensitivity and specificity were calculated and results synthesised and compared narratively.
Results 27,575 search results returned 18 eligible studies, examining 13 index tests, against five reference tests, for their accuracy in detecting 24 molecular markers. Some markers and tests were investigated multiple times, but rarely in the same combinations. Characteristics of studies were poorly reported. Generally, risk of bias and applicability concerns were unclear. Estimates of sensitivity and specificity were calculable for most evaluations, confidence intervals were generally wide.
Discussion Estimates of the accuracy of molecular methods are generally imprecise, contributing to uncertainty. Many methods may be close to 100% in sensitivity or specificity. Most methods require specialist equipment unlikely to be available in many low resource settings. High quality study design focusing on methods useable in low resource settings, prospective registration, and reporting according to STARD 2015 guidelines are essential for future studies.

Keywords: Meta-analysis
Drug resistance
Diagnostic test accuracy
Narrative synthesis
Malaria
Molecular methods
Systematic review
Plasmodium falciparum
Advisor: Papoutsi, C
Fanshawe, T
Butler, C
Soft chemical control of layered oxychalcogenides

The structure, magnetic behaviour and chemistry of layered oxychalcogenides of composition A2MO2X2Ch2 (where A = Sr, Ba; M = Mn, Co, Ni, Cu, Zn; X = Cu, Ag and Ch = S, Se, Te) has been investigated by the synthesis of new compounds of this type and control of the properties of these compounds by oxidative deintercalation of Cu/Ag.
I2 can be used to oxidatively deintercalate Cu from Sr2MnO2Cu1.5S2, forming Sr2MnO2Cu1.33S2, an incommensurately modulated compound, with a completely different Cu/vacancy ordering and antiferromagnetic ordering structure to the parent. This reaction is also probed in real-time, using in situ powder X-ray diffraction.
Sr2MnO2Ag1.5Se2 was found to have an A-type magnetic ordering structure, similar to Sr2MnO2Cu1.5Se2. Sr2MnO2Cu1.8Te2 on the other hand with a lower Mn oxidation state shows only two-dimensional magnetic correlations, rather than long-range order.
Extending the reaction with I2 to several Co-containing analogues revealed that &Tilde; 25% Ag could be removed from Sr2CoO2Ag2Se2, sufficient to observe a change in magnetic behaviour, from antiferromagnetic to ferromagnetic. By contrast only &Tilde;11% Cu can be deintercalated from Sr2CoO2Cu2S2 and even less (&Tilde;5%) from Sr2CoO2Cu2Se2. Neutron diffraction was used to examine the resultant changes in magnetic ordering.
The novel compounds Sr2CuO2Cu2Se2 and Ba2CuO2-xCu2Se2 are related by substitution of the alkali-earth metal, but while Sr2CuO2Cu2Se2 is a stoichiometric compound with metal-like character, Ba2CuO2-xCu2Se2 is an oxygen-deficient semiconductor, with tuneable oxygen content.
Unusual features are observed in the magnetic susceptibility measurements of Sr2NiO2Cu2Se2 that appear unrelated to this compound's long-range magnetic ordering, as probed by neutron diffraction. Furthermore, unusual peak splitting is observed in low-temperature powder X-ray diffraction patterns of this compound; this may plausibly be due to a photon-induced effect arising from the use of a high-energy beamline; although further measurements are required to examine this.
Overall the work shows the flexibility and range of behaviour exhibited by a series of the transition metal oxide chalcogenides.

Keywords: Oxide chalcogenides
Magnetism
Magnetic order
Solid-state chemistry
Oxychalcogenides
Advisor: Clarke, S
Sensorimotor cortex plasticity in upper-limb amputees

The current thesis was aimed at investigating how the primary sensorimotor cortex, and in particular the missing hand cortex, is affected by upper-limb amputation. This thesis further explores how activity in this region relates to phantom limb pain (PLP). As such, a series of neuroimaging experiments was designed, aimed at answering 3 main questions: 1) What happens to the neural fingerprint of a hand following its amputation? 2) What are the behavioural and neural underpinnings of PLP? 3) Can novel targets for PLP treatment be identified?
By making use of ultra-high field 7 tesla fMRI and the phenomenology of phantom limb sensations, this thesis demonstrates that the topographical representation of a missing hand’s individual digits is preserved in primary somatosensory cortex, even decades after arm amputation. This finding of stable topography questions the extent to which continued sensory input is necessary to maintain organisation in sensory cortex.
Slowed phantom hand motor control was identified as a behavioural correlate of chronic PLP. Stronger maintained activity in the primary sensorimotor missing hand cortex was reaffirmed as a neural correlate of chronic PLP and was further associated with deteriorated phantom hand motor control. This thesis presents results challenging the maladaptive plasticity model and instead emphasising a likely relationship between persistent peripheral inputs pertaining to the missing hand representation and chronic PLP.
Anodal tDCS over the primary sensorimotor missing cortex during a phantom hand movement task effectively relieved PLP with effects lasting at least one week post stimulation. In accordance with above, amputees with more PLP relief showed less activity in the primary sensorimotor cortex after brain stimulation. Importantly, tDCS-concurrent neuroimaging identified the insula and secondary somatosensory cortex as neural correlates of PLP relief and subsequent sensorimotor cortex downregulation.
Together, this thesis reveals new roles of primary sensorimotor cortex following arm amputation and provides a first comprehensive overview of the neural mechanisms underlying missing hand sensations, offering novel opportunities for PLP treatment.

Advisor: Makin, T
Johansen-Berg, H
Beckmann, C
Resource theories of quantum coherence: foundations and applications

One of the fundamental features that separates quantum physics from classical physics is the idea of quantum superposition, also known as coherence. This thesis concentrates on understanding quantum coherence in the mathematical framework of resource theories, viewing it both as a resource to be harnessed and as a way to quantitatively characterise quantum states in contrast to classical states.
We first examine the type of coherence resource theory which has emerged recently to cope with general settings where the physical nature of the medium encoding information is not crucial, such as computation. We identify the set of quantum processes in which coherence is neither created nor used, and use these to provide a physically motivated resource theory pictured in terms of interferometry. Using the same concepts, we then find connections between coherence and discord, a type of quantum correlation. In particular, we show how coherence can be used to generate discord, and explore basis-dependent discord as an intermediate quantity.
The second part of the thesis applies the resource theory framework to quantify quantum macroscopicity, taken here to mean the extent to which coherence exists in a system on a macroscopic scale. We find the appropriate type of resource theory for this purpose, giving criteria for good measures of macroscopic coherence. We use these criteria to evaluate some previously proposed measures and highlight the role of the quantum Fisher information. Next, we build up measures based on the concept of macroscopic distinguishability and use them to show that macroscopic quantum states are fragile to noise induced by interaction with an environment. Finally, we apply measures based on the Fisher information to a range of experiments involving mechanical degrees of freedom, in order to compare their macroscopicity.

Advisor: Vedral, V
Altered function of CCK-positive interneurons in mice over-expressing the schizophrenia risk gene neuregulin 1

The Neuregulin 1 (NRG1)-ErbB4 signalling pathway is implicated in critical processes for the development and function of neuronal circuits. Post mortem studies have reported that elevated expression of NRG1 type 1 isoform is associated with schizophrenia. Importantly previous behavioural studies in mice that overexpress the NRG1 type 1 isoform (NRG1tg-type-I) have suggested a schizophrenia endophenotype including impairment in the hippocampus-dependent spatial working memory, prepulse inhibition (PPI) of the startle reflex and alterations in the gamma band rhythmogenesis This study aims to reveal the cellular targets of the NRG1-ErbB4 signalling pathway and putative alterations in the function of the hippocampal network in NRG1tg-type-I mice.
Immunocytochemical analysis showed that the NRG1 receptor ErbB4 is predominantly localized in interneurons comprising parvalbumin positive (PV) and cholecystokinin (CCK) expressing cells. Comparison of the density of ErbB4-positive cells between the hippocampus of wild type (WT) and NRG1tg-type-I mice suggested that NRG1 over-expression resulted in decreased number of ErbB4 immunopositive hippocampal interneurons. This is consistent with the proposed role of the NRG1-ErbB4 signalling in the migration of GABAergic cells during neurodevelopment and with the NRG1-mediated internalisation of the ErbB4 receptors. CCK- positive cells are a major target of NRG1-ErbB4 signalling, and therefore the NMDA receptor and AMPA receptor components of glutamatergic transmission were analysed in this population of cells by performing whole cell recordings of evoked and miniature excitatory post synaptic currents. Glutamatergic neurotransmission in CCK-positive cells was found to be compromised in the hippocampus of NRG1tg-type-I mice. This change was attributed to hypofunction of NMDA receptors but not AMPA receptors post-synaptically. Next, the inhibitory output of CCK-positive cells to pyramidal cells was examined. Analysis of the optogenetically elicited inhibitory post synaptic currents (IPSCs) did not reveal any changes in the properties of the GABAergic synapse formed by these cells due to NRG1 over-expression Finally, the effects of this NMDA receptor hypofunction in the recurrent inhibition were analysed by performing whole cell recordings during the gamma relevant optogenetic entrainment of the hippocampal network. It was found that the disynaptic inhibition, a key synaptic interaction for the generation of gamma oscillations, depends on the NMDA receptors and was altered in the hippocampus of NRG1tg-type-I mice.
Together these data point out a key modulatory role of the NRG1-ErbB4 signalling in the neurodevelopment of cortical microcircuits and a link between ErbB4 and NMDA receptor function with a possible association to schizophrenia pathogenesis.

Keywords: Neurophysiology
Neuregulin
Schizophrenia
Hippocampus
Interneurons
Physiology
Advisor: Lamsa, K
Minichiello, L
Between cosmopolitan and classical: Persian in early colonial India, c.1757-1857

This thesis investigates the significance of Persian learning in Britain and India during the period of colonial expansion under the East India Company, from 1757 to 1857. It seeks to situate Persian in its wider social context in north India, and understand the significance and function of the language during a period which is typically described in terms of the decline of the Persianate world. It does so by studying Persian literary production and language-learning by a range of actors at different sites in north India. By examining the presence of Persianate texts and individuals in spaces and endeavours which are typically classified as modern (orientalist textual production in the colony, the rise of linguistic studies, colonial education and nineteenth-century Indian printing), this thesis emphasizes the ways in which Persianate relationships and sensibilities shaped these sites of Indian modernity, and were themselves altered in the process. This thesis shows that the reasons for the continued usage of Persian in late eighteenth and early nineteenth-century India went beyond its symbolic value as a marker of earlier Mughal power. Persian played an important role in shaping and constructing cosmopolitan literary and scholarly identities, as well as enabling spatial and social mobility. In so doing, this thesis hopes to contribute to the historiography of the Persianate world, as well as the histories of language, printing and education in colonial South Asia more broadly. In making these arguments, this thesis suggests a reappraisal of the ways in which the relationship between Indian modernity and cosmopolitan cultures now seen as 'classical' - such as that of Persian - is conceived. Rather than viewing Persian as a mere symbol of Mughal rule, a socially-grounded understanding of the Indian and colonial engagement with Persian is suggested. Understanding Persian in its social context in India, and recognizing the variety of spaces, languages and groups it interacted with challenges any neat categorization of the language as 'classical' or 'foreign' to India, or in opposition to vernacular or indigenous languages.

Keywords: Colonial India
Persianate World
Advisor: Misra, M
Grey, D
MAIT cells in sterile and non-sterile inflammation

Mucosal-associated invariant T (MAIT) cells are an innate-like T cell subset that recognize bacteria-derived metabolites presented on MR1, but can also be stimulated in a T cell receptor (TCR)-independent manner by pro-inflammatory cytokines. Therefore, their role in both sterile and non-sterile diseases are of great interest and only just beginning to be explored. To understand the role of MAIT cells in non-sterile inflammation, we utilized a controlled human infection model of live Salmonella enterica serovar Paratyphi A. We observed that at the time of diagnosis MAIT cells had an activated phenotype, which was maintained even after antibiotic treatment. We analysed the TCR repertoire of MAIT cells in diagnosed individuals to determine if the MAIT cell response to infection was antigen- driven. We found that infection led to redistribution of the repertoire, with transient contraction of the over-represented clones at the peak of infection. To understand the role of MAIT cells in sterile inflammation we examined cancer sections and found that MAIT cells infiltrate tumours derived from various tissues and that the source of MAIT cells was from tissue-resident MAIT cell subsets. We also determined that MAIT cells may respond to BCG immunotherapy of bladder cancer, as they are both present and activated in the bladder following treatment. Finally, we wanted to determine the extent to which both the TCRα and TCRβ usage affected MAIT cell responses. We found that the TRAJ usage, which relatively defines circulating versus tissue-resident MAIT subsets, has a large impact on the MAIT TCR response to both bacterial and ligand stimulation. We also investigated selected TCRβ clonotypes identified in Salmonella-infected individuals and found that the MAIT cell clonotypes that expanded after infection had stronger TCR-dependent activation than did contracted clonotypes from the same individual. In conclusion, we have characterised the function and phenotype of MAIT cells in human infection, cancer and cancer immunotherapy as well as provide insight into the usage and importance of the specific MAIT cells TCRα and TCRβ chains.

Keywords: Salmonella
MAIT
Cancer
Advisor: Cerundolo, V
Nomads in the liberal state: liberal approaches to the problem of Roma and traveller itinerancy

May the state, from a liberal point of view, operate laws and institutions that impede the mobile lifestyle of nomadic Roma and Travellers, or should the state take steps to accommodate their nomadic way of life? This is the essence of the problem of Roma and Traveller itinerancy and the question that is at the heart of this three-partite dissertation.
The first part of the dissertation looks at public policy in France and the United Kingdom and describes the six public policy problems that constitute the problem of Roma and Traveller itinerancy. These problems concern the education of children, the French travel permits system, the legal conditions for voter registration and for GP registration, the housing benefits system, and the public provision of halting sites.
The second part looks at liberal political theory. It suggests that contemporary liberalism divides into two strands that take different views on the entitlements of cultural and religious minorities, and it provides a detailed outline of the prime articulations of each approach, namely the multiculturalist liberalism of Kymlicka and the classic neutrality liberalism of Barry.
The third part investigates what the two said liberalisms imply for the six policy problems from part 1. These analyses suggest that the two liberalisms have slightly diverging implications for the halting sites problem, the housing benefits problem and the problem of GP registration. They suggest furthermore that the two accounts converge on the question of voter registration and agree that the voter registration system must accommodate nomads, and may not make the possession of a fixed residence an absolute condition for voter registration. And the analyses suggest finally that the two liberalisms also converge over the education question and the travel permits question, but here support polices that are potentially inimical to Roma and Traveller itinerancy. The broader implications of these findings are that liberalism is potentially, but not necessarily and not intrinsically, inimical to Roma and Traveller nomadism, and that the disagreement between classic neutrality liberalism and multiculturalist liberalism is weak insofar as public policy is concerned.

Keywords: multiculturalism
minority rights
Roma and Travellers
gens du voyage
liberalism
Brian Barry
Will Kymlicka
nomadism
Advisor: Miller, D
An arterial spin labelling method for the measurement of myocardial perfusion in humans at 3 tesla

The assessment of Myocardial Blood Flow (MBF) is an important measure in clinical practice for evaluating the health of the heart. Multiple imaging methods have been employed to measure MBF, including applications of nuclear medicine, x-ray and contrast enhanced Magnetic Resonance Imaging (MRI). However, each of these modalities suffers from drawbacks, such as invasiveness due to radiation or intravenous contrast injection, difficulty in quantitation, and limited repeatability.
The aim of this thesis was to develop a non-invasive, quantitative and repeatable MRI method for the measurement of MBF, by applying the techniques of Arterial Spin Labelling (ASL). A novel cardiac ASL sequence was designed and thoroughly tested by simulation and phantom experiment. The method was applied in vivo in three slices of the human heart, to our knowledge the first cardiac ASL acquisition in multiple slices, in ten healthy volunteers. The resulting values of mid-ventricular MBF, averaged over multiple measurements, compared well with the literature values from multiple modalities. Repeat measures were then used in order to characterise the reproducibility and variation inherent in the method, showing that the expected change in MBF would be detectable with the ASL sequence. Segmental values of MBF, according to the AHA standard model, were also calculated and these compared well to previous PET literature. This work has been published in the journal Magnetic Resonance in Medicine.
Further to this work, the new cardiac ASL sequence was optimised with the ultimate goal of single breath hold acquisitions. The optimised sequence was shown to improve the results in terms of the balance between good signal-to-noise ratio and reducing spatial and temporal variation in MBF values. Though improvements were made, there remained a large variation in the measured values of MBF, meaning single breath hold acquisition in a clinical context is not yet practical. In addition to the optimisation, the online scanner reconstruction software was altered to produce parametric maps of both T1 and MBF direct to the scanner operator. The sequence, along with online reconstruction is available for use in our laboratory for future clinical trials in the heart and liver.

Keywords: Magnetic Resonance Imaging
Arterial Spin Labelling
Myocardial perfusion
Advisor: Keith, G
Robson, M