VictorJuiz/thesis huggingface dataset:
Unravelling the links between psychotic-like experiences, sleep and circadian rhythms

Psychotic-like experiences (PLEs) are prevalent occurrences deemed comparable with the symptoms of psychosis, but not sufficiently severe to warrant a diagnosis upon clinical presentation. Their presence is associated with several adverse clinical outcomes: the onset of various common mental health disorders (e.g. anxiety, mood, substance abuse), poorer functioning, non-remission and relapse.
Sleep and circadian rhythm disruption (SCRD) is observed in 30-80% of patients with psychosis. The omnipotence of SCRD across all phases of the disorder (including the prodromal, acute, chronic and residual phases) raises the question as to whether SCRD may directly contribute to the development of psychosis. Assuming that PLEs are along the same continuum to developing psychosis, a logical next step to further disentangle the sleep-psychosis relationship is to examine whether SCRD relates to the experience of PLEs and whether this relationship is bi-directional.
This thesis begins by examining the core predictions made by a continuum model of understanding psychosis and how specific parameters of sleep may influence PLEs. A smaller high-definition cross-sectional study follows, examining biological underpinnings (electroencephalography (EEG), electrocardiography (ECG), endogenous melatonin rhythms and actigraphy) of a complaint of poor sleep and their relation to the occurrence of PLEs. We then refocus on which parameters of sleep are most integral to the sleep-PLE relationship and close with an investigation of how Hypothalamic Pituitary Adrenal (HPA) axis activity may further our knowledge of this relationship.
The findings of this thesis demonstrate specificity in the parameters of sleep shown to impact certain PLEs. The importance of objective sleep and biologically driven measures in this line of research are underscored, with group differences in EEG, ECG and melatonin. This thesis also highlights dissociative symptomatology as a candidate mediator for the sleep-psychosis relationship, and emphasises the ties between paranoia and negative affect. Finally, this thesis also illuminates the challenges of examining the relationship between sleep and PLEs in isolation, and suggests that they must be considered within the broader framework of co-existing mental health problems.

Keywords: heart rate variability
cortisol
acitgraphy
insomnia
melatonin
circadian rhythms
polysomnography
sleep
psychotic experiences
Advisor: Wulff, K
der Kloet, D
Bacterial protein import mediated by an iron transporter

Multidrug resistant bacteria (MDR) have the potential to push back society to the pre-antibiotic era. Although discovered before penicillin, the inexorable rise in antibiotic resistance has revitalised interest in bacteriocins as treatments for bacterial infections. Bacteriocins are protein antibiotics principal to competition amongst pathogens and commensals, but the mechanisms by which they translocate across the Gram-negative cell envelope are poorly understood. The work presented in this thesis demonstrates how the endonuclease bacteriocin pyocin S2 (pyoS2) exploits the iron transporter FpvAI to translocate across the outer membrane (OM) of Pseudomonas aeruginosa. FpvAI is a 22-strand β-barrel and virulence factor in P. aeruginosa that transports iron into the cell in the form of a small siderophore, ferripyoverdine (Fe-Pvd). Uptake of Fe-Pvd requires the proton motive force (PMF), which is transduced to the ligand-bound receptor by TonB1 and its partner proteins ExbB-ExbD in the inner membrane (IM). The crystal structure of the high affinity complex (Kd = 240 pM) formed between the N-terminal domain of pyoS2 (pyoS2NTD) and FpvAI is presented, which shows pyoS2NTD mimics Fe-Pvd, and induces the same conformational changes in the receptor. Fluorescently-labelled pyoS2NTD was actively imported into P. aeruginosa PAO1 cells and this import was dependent on the PMF, TonB1 and a TonB1-box motif at the N-terminus of pyoS2NTD. Finally, photo-activated crosslinking of stalled translocation intermediates demonstrated pyoS2NTD translocates through the FpvAI β-barrel lumen by a process analogous to that of Fe-Pvd. Following binding to FpvAI, translocation begins by the unfolding of a force-labile portion of the plug domain, opening a narrow channel through FpvAI. This enables pyoS2 to deliver its own TonB1-box to the periplasm where contact with TonB1 activates its import through the same channel, most likely as an unfolded polypeptide. Hence, this study demonstrates that bacteria possess a rudimentary protein import system that exploits energised nutrient transporters in the OM.

Keywords: Transporter
Antibiotic
Outer membrane receptor
Pseudomonas aeruginosa
Pyocin
Advisor: Kleanthous, C
Hugh Broughton (1549-1612): scholarship, controversy and the English Bible

This thesis provides a revisionist account of the relationship between Latin biblical criticism, vernacular religious culture and Reformed doctrines of scriptural authority in the early modern period. It achieves this by studying episodes from the career of the English Hebraist Hugh Broughton (1549-1612). Current orthodoxy holds that Broughton’s devotion to the tenets of Reformed scripturalism distinguished him from contemporary biblical humanists, whose more flexible attitudes to the Bible enabled them to produce cutting-edge scholarship. In challenging this consensus, this thesis focusses on three areas.
The first is chronology. Recent work has presented chronology as divided between technical, philological practitioners, who drew from astronomy and humanism alike in their efforts to date the past, and scripturalists, who relied on the Bible alone. Using the chronological controversy between Broughton and the Oxonian John Rainolds, this thesis complicates this picture by arguing that both approaches to the discipline were equally derived from humanistic traditions, and that confessional, rather than intellectual or methodological, factors informed the most important decisions chronologers made.
The second area is biblical criticism. There is still a broad assumption that Reformed beliefs about scripture were incompatible with the most advanced biblical scholarship. This thesis questions such assumptions by reconstructing Broughton’s research into the Hebraic contexts of the New Testament. By demonstrating that it was possible to produce innovative and influential work without challenging and indeed, while endorsing the principles of Reformed scripturalism, this thesis disputes current teleological presumptions about the development of modern, historical biblical criticism.
The third is the history of lay reading. Both chronology and biblical criticism have often been viewed as specialised pursuits, studied only by a Latin-reading elite and irrelevant to lay people. For Broughton and his followers, however, biblical scholarship and lay piety were inseparable. The thesis demonstrates this by piecing together Broughton’s radical plans for a new English Bible, including his work with John Speed on biblical genealogy, and his revisions of the Geneva New Testament. Using numerous neglected manuscript sources, it gives an account of the sixteenth-century biblical translation that foregrounds the unexpected ways in which groundbreaking neo-Latin, continental biblical scholarship expanded scholars' concepts of what vernacular translation could achieve.

Keywords: Bible
Intellectual History
New Testament Scholarship
Hugh Broughton
King James Bible
Biblical scholarship
English Bible
Sixteenth-century England
Early Modern History
Chronology
Biblical genealogy
Advisor: McCullough, P
Weinberg, J
On the semantics of intensionality and intensional recursion

Intensionality is a phenomenon that occurs in logic and computation. In the most general sense, a function is intensional if it operates at a level finer than (extensional) equality. This is a familiar setting for computer scientists, who often study different programs or processes that are interchangeable, i.e. extensionally equal, even though they are not implemented in the same way, so intensionally distinct. Concomitant with intensionality is the phenomenon of intensional recursion, which refers to the ability of a program to have access to its own code. In computability theory, intensional recursion is enabled by Kleene’s Second Recursion Theorem.
This thesis is concerned with the crafting of a logical toolkit through which these phenomena can be studied. Our main contribution is a framework in which mathematical and computational constructions can be considered either extensionally, i.e. as abstract values, or intensionally, i.e. as fine-grained descriptions of their construction. Once this is achieved, it may be used to analyse intensional recursion.
To begin, we turn to type theory. We construct a modal λ-calculus, called Intensional PCF, which supports non-functional operations at modal types. Moreover, by adding Löb's rule from provability logic to the calculus, we obtain a type-theoretic interpretation of intensional recursion. The combination of these two features is shown to be consistent through a confluence argument.
Following that, we begin searching for a semantics for Intensional PCF. We argue that 1-category theory is not sufficient, and propose the use of P-categories instead. On top of this setting we introduce exposures, which are P-categorical structures that function as abstractions of well-behaved intensional devices. We produce three examples of these structures, based on Gödel numberings on Peano arithmetic, realizability theory, and homological algebra.
The language of exposures leads us to a P-categorical analysis of intensional recursion, through the notion of intensional fixed points. This, in turn, leads to abstract analogues of classic intensional results in logic and computability, such as Gödel's Incompleteness Theorem, Tarski's Undefinability Theorem, and Rice's Theorem. We are thus led to the conclusion that exposures are a useful framework, which we propose as a solid basis for a theory of intensionality.
In the final chapters of the thesis we employ exposures to endow Intensional PCF with an appropriate semantics. It transpires that, when interpreted in the P-category of assemblies on the PCA K1, the Löb rule can be interpreted as the type of Kleene’s Second Recursion Theorem.

Advisor: Abramsky, S
Commitment issues: toward an understanding of young people's social media choices in the multi-platform era

Social network sites (SNSs) have become a common part of everyday life for billions of people worldwide. Not everyone uses the same sites, nor are sites functionally equivalent in the eyes of users. Both established platforms and new upstarts may provide novel features or access to new audiences, yet users tend to remain on a few dominant platforms, especially Facebook, the world’s reigning social network site. The goal of the present study is to understand why people are committed to specific social network sites, given that no site encompasses either all of a person’s social connections or all possible gratifications available from online participation. Further, individuals do not always wish to have a single real-name identity for all online interactions, thus implying the necessary use of multiple accounts or sites. To understand SNS commitment, this study employs a mixed-methods research design by combining findings from a survey of 800 respondents with 50 semi-structured interviews. The research focuses on young adults in the UK and their use of four popular SNSs: Facebook, Twitter, Instagram and Snapchat.
Findings indicate that network size has only a marginal effect on commitment, whereas the effect of identity performance is more pronounced, albeit in different ways on different sites. Social and informational gratifications have the strongest effect across all four SNSs, suggesting that commitment is primarily driven by repeated habit-forming experiences. To further help explain SNS commitment, this thesis employs a typology of social media users based on attitudes towards digital technology. It is evident that attitudes explain more variation in commitment than either demographic factors or personality. Qualitative analysis reinforces this finding by showing how users employ specific gratification-based repertoires to determine which sites to use and when. These findings help advance research on affordances, self-presentation and SNS use, while also making practical recommendations for social media platforms.

Keywords: Technology adoption
Platform engagement
Self-presentation
Social networking
Affordances
Social media choice
Uses and gratifications
Advisor: Hogan, B
Reed-Tsochas, F
Management of hypertensive disorders of pregnancy in the postpartum period

This thesis aimed to explore whether self-management techniques, effective in essential hypertension, could be applied to women with hypertensive disorders of pregnancy postpartum (HDP). HDP affect one in ten pregnancies, remain a leading cause of maternal death worldwide and are associated with elevated long-term maternal cardiovascular risk. Hypertension often persists postpartum and complications can occur. During the puerperium, multiple stresses on new mothers and their healthcare professionals can distract from good quality blood pressure (BP) management. Transfer of responsibility, from secondary to primary care, increases scope for uncertainty. The primary objective was to develop and test the feasibility of a novel self-management intervention for postnatal antihypertensive treatment.
A systematic literature review (39 studies), local audit (n=20) and regional survey (n=101) were conducted to evaluate existing evidence and clinical practice. A pilot randomised controlled trial compared self-management of postnatal antihypertensive medication with usual care (n=91). Taking patients' views of self-management into account is essential to successful implementation and these were captured through qualitative interviews (n=68). A sub-study to assess markers of vascular risk (n=16) was conducted to further evaluate the relationship between postnatal BP and elevated long-term cardiovascular risk.
There is a lack of good quality evidence underpinning hypertension management postpartum and widespread inconsistencies in approaches to care. The pilot trial suggested that expanding the study would be feasible, and that self-management may be more effective than usual care in terms of BP control. Strikingly, the 4-5mmHg reduction in diastolic BP observed with self-management persisted to six months, despite the majority of women being off treatment by this stage, reinforcing the idea that BP control during the puerperium may influence cardiovascular remodelling. However, no differences were demonstrated in markers of cardiovascular risk between sub-study groups. Participants commonly preferred self-management to usual care, and reported feeling more in control through this approach.

Keywords: Gestational hypertension
Self-monitoring
Pre-eclampsia
Telemonitoring
Postpartum
Advisor: McManus, R
Leeson, P
Tucker, K
Powell, J
Layered double hydroxides for packaging applications

The primary aim of this thesis is to synthesise and modify layered double hydroxides (LDHs) for using in packaging applications.
Chapter One provides an introduction of the basic manufacturing process of paper-based and flexible packaging and the relevant aspects of using inorganic materials in packaging materials. The principles of gas permeation and the role of two-dimensional platelets on the concept of a tortuous pathway are reviewed. In addition, the structure, synthesis methods and applications of LDHs are presented.
Chapter Two details the synthesis of LDH/cellulose fibre composites and their use as fillers in the papermaking process. The strength and optical properties of the obtained LDH/cellulose fibre based paper sheets are examined. Superhydrophobic organo-LDHs are synthesised and applied as a pigment in a water resistant coating for paper.
Chapter Three describes the novel post treatment for LDHs using aqueous immiscible solvents (AIM solvents). The effect of solvent functional groups and structure, along with some post treatment parameters such as rising volume, dispersion time, Mg/Al ratios, and solvent recycling on physicochemical properties of AIM LDHs are explored. The interactions between solvents and LDHs via hydrogen bonding are investigated using solid state nuclear magnetic resonance spectroscopy (SSNMR).
Chapter Four presents the preparation of LDH nanoplatelets using a reconstruction of layered double oxides (LDOs) in a concentrated aqueous solution of amino acids. The effect of amino acid structure and other highly water-soluble compounds on the textural and chemical properties of the reconstructed LDHs are examined. The LDH nanoplatelets produced are used to formulate water-based dispersions for coating on polyethylene terephthalate films (PET). The effect of LDHs morphology, number of coating layers and loading amount of LDHs in the coating dispersion on an oxygen barrier performance and optical properties of the coated PET films are discussed.
Chapter Five provides an alternative method for preparation of LDH nanoplatelets using direct reconstruction of LDOs in water, water-soluble polymer (polyvinyl alcohol or PVA), and non aqueous solvents. The effects of calcination temperature, reconstruction time, LDHs morphology, and PVA selection on the structural and physical properties of the reconstructed LDHs were investigated. Finally, the directly reconstructed LDHs are formulated into the coating dispersions and applied on PET films. The oxygen barrier and optical properties of the coated PET films are evaluated.
Details of the experimental procedures performed are included in Chapter Six. Supplementary information and data referred to in the main thesis are found in the Appendices.

Advisor: O'Hare, D
Clinical and functional characteristics of seronegative and musk myasthenia gravis

Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction (NMJ). Most patients have antibodies (Abs) against the acetylcholine receptor (AChR) or muscle specific kinase (MuSK) detected by radioimmunoassays (RIAs). Cell-based assays can more sensitively detect these and other Abs (e.g. to low density lipoprotein receptor-related protein 4 (LRP4)) but no large cohorts of MG patients have been systematically studied. RIA positive MuSK-Abs are mainly IgG4 subclass and block the interaction between LRP4 and MuSK, resulting in reduced MuSK phosphorylation and agrin-induced AChR clustering at the NMJ. MuSK phosphorylation could provide a potential therapeutic target.
An international cohort of 231 MG patients negative for AChR and MuSK Abs by RIA, were tested with CBAs for all three known antigens. Negative sera were screened for novel antigenic targets by immunoprecipitation and mass spectrometry (IP/MS). MuSK phosphorylation was assessed in cultured mouse C2C12 myotubes treated with MuSK-MG IgG subclass fractions. The formation, dispersal, and re-formation of AChR clusters by MuSK-Abs in the presence or absence of a tyrosine phosphatase SHP2 inhibitor (NSC-87877) were measured quantitatively.
First, the detection of MuSK-IgG Abs by CBA was optimised, and the potential relevance of the antibodies shown by their ability to reduce agrin-induced AChR clusters in the myotubes. Overall, AChR-Abs (10%), MuSK-Abs (7%) and LRP4-Abs (&LT;1%) antibodies were newly identified. Five negative sera bound to human muscle cell lines, but no plausible novel antigens were identified by IP/MS. MuSK-MG IgG4 fractions inhibited MuSK phosphorylation, which was restored by SHP2 inhibition. SHP2 inhibition also increased AChR cluster formation, blocked dispersal and increased re-formation of AChR clusters by MuSK-Abs.
As discussed, finding new antibody targets in MG was confounded by testing patients who were no longer severely affected following immunotherapies. MuSK-MG, by contrast, is frequently severe and modifying phosphorylation of MuSK and its downstream signalling pathways may provide a novel treatment approach for this and other forms of MG.

Advisor: Vincent, A
Beeson, D
Improving cardiovascular risk prediction through more accurate and alternative  methods of blood pressure measurement

Background
Cardiovascular risk scores are used to estimate absolute risk of disease and identify patients who will benefit most from treatments to lower risk. As a key risk factor for cardiovascular disease, blood pressure is accounted for in many risk scores, but is inherently variable and may be influenced by both biological and measurement factors. This thesis aims to determine how routinely collected blood pressure measurements should best be used for accurate estimation of cardiovascular risk.
Methods
This thesis describes four main studies. A patient survey and prospective study establish the current practice of blood pressure measurement. Secondary analyses of data from blood pressure monitoring trials determine how risk estimates may be affected by the use of different summary measures of blood pressure. A systematic review evaluates the evidence of an association between blood pressure variability and cardiovascular risk. Finally, a cohort study in the Clinical Practice Research Datalink determines if inclusion of blood pressure variability in cardiovascular risk scores may improve risk estimation.
Results
Current practice of blood pressure measurement may differ from that in risk score derivation studies. However, these differences have limited effects on cardiovascular risk estimates with few patients reclassified across risk thresholds. Increased long-term variability in blood pressure is in itself a risk factor for cardiovascular disease over and above mean blood pressure but its inclusion in a cardiovascular risk score does not materially improve the accuracy of risk estimates.
Conclusions
Healthcare professionals should continue to estimate risk for primary prevention of cardiovascular disease using the blood pressure measurements available to them, whether measured at home or in the clinic. There is also no additional benefit of considering measures of long-term blood pressure variability in risk estimation.

Keywords: blood pressure
cardiovascular disease
risk
Advisor: Stevens, R
McManus, R