VictorJuiz/thesis huggingface dataset:
Mortality inequality and its implications for retirees

This thesis presents four studies on mortality inequality which advance the knowledge of how lifespans differ across social groups and the implications for retirees. The first two studies are based on the concept of distributional differences and propose new methods to study mortality inequality. Specifically, Chapter 2 introduces a statistical distance index to capture the stratification of lifespans among social groups. Empirical evidence from Finland demonstrates its utility and reveals new dimensions of mortality inequalities that traditional measures obscure. Chapter 3 proposes a novel method for investigating the factors that contribute to total lifespan inequality. It finds that in the United States, while racial/ethnic differences in life expectancy contribute little to total-population-level lifespan variance, distributional differences across race/ethnicity explain one fifth of the total lifespan variance. The next two studies explore the implications of mortality inequalities for retirees. Chapter 4 models dynamic work trajectories of older US adults and presents major results of gender and educational inequalities in the United States. It shows that less-educated older adults spent less time working, which compensates for their lower longevity when compared to their more-educated counterparts. Nonetheless, educational inequality in retirement lifespan is substantial and persistent. Chapter 5 looks at how education and preretirement earnings relate to lifetime pensions from age 60 onward, as well as how mortality affects the distribution of lifetime pensions in Sweden. The results show that the greater longevity of socially advantaged groups accounts for up to one quarter of lifetime pension inequality. Chapters 4 and 5 both highlight the importance of social differences in mortality and advocate for greater emphasis on the role of mortality in high-level discussions on old-age policies.

Keywords: retirement
aging
social stratification
demography
inequality
life course
mortality
Advisor: Monden, C
van Raalte, A
Harry A. Williams beyond Soundings: finding God through self-awareness and doubt

This thesis examines the life and work of Harry Abbot Williams, CR (1919-2006), an Anglican priest and theologian, who was one of the most well-known Church of England clergymen of his time, exerting an influence well beyond the Church. His life was marked by a deep struggle of conflicting claims and tensions and his writings are infused with a profound psychological sense lending to them a compelling impact.
As a homosexual priest initially suppressing his sexual orientation, Williams suffered a mental breakdown which triggered feelings of profound guilt, disapproval and mental paralysis. This experience was for him pivotal; his public admission of homosexuality in his autobiography published in 1982 was one of the first examples of a prominent Anglican clergyman coming out.
There is at present no monograph or critical study of the life and work of Williams, although he was frequently seen as one of the most popular, attractive and persuasive writers on personal religion in contemporary England. The thesis thus aims at an original contribution bridging a gap in an under-researched chapter of the history of 20th century Anglican theology.
The main argument of the thesis is that in a situation where, until the 1960s, academic discourse especially in theology was frequently dominated by an underlying conservatism, Williams and his contemporaries played a central role in defining the radical movement in the Church of England. They contributed significantly to the cultural revolution experienced in 1960s Britain: in the field of Anglican theology, a radically alternative framework for understanding Christianity and the contemporary world was being established, which refused to equate Christianity with conventional respectability.

Keywords: Harry A. Williams CR (1919-2006)
20th century Anglican theology
Advisor: Chapman, M
Understanding the role of PRMT5 in neuroblastoma

Neuroblastoma (NB) is a deadly childhood cancer that has an orphan disease status, and the most malignant forms of the tumours have MYCN amplification. There is significant unmet medical need and urgency to develop new treatments for high-risk NB patients, as clinical research on rare diseases of children is very challenging. We revealed that higher PRMT5, MYCN, and E2F1 levels are poor prognostic factors in NB according to their Kaplan-Meier survival plots and then we hypothesized that PRMT5-E2F1-MYCN pathway might have potential prognostic value in NB. We characterized NB cell lines in terms of sensitivity to the PRMT5 inhibition by using genomic and transcriptomic assays in order to gain better insight into the underlying molecular mechanism of sensitivity to PRMT5 inhibition. We used T1-44 compound to inhibit PRMT5 biochemically. We found that MYCN amplified NB cancer cells were significantly more sensitive to the PRMT5 inhibition (p <0.0062) and T1-44 treatment induced higher number of differentially expressed and alternatively spliced events in the high E2F1/MYCN expressing cell line when compared with the low E2F1/MYCN expressing cell line. We characterized differentially spliced apoptotic genes upon 200 nM treatment with T1-44 for 72 hours as these genes might have a functional impact on cell fate, we found that T1-44 induced differential splicing of apoptosis genes BCL2L11 and CDK10 in MYCN amplified compared with non-MYCN amplified NB cells. Our results highlight the role of the PRMT5, E2F1, and MYCN axis in the alternative splicing pathway and its clinical relevance in MYCN amplified NB patients. MYCN amplification is observed in many other cancer types beyond NB. Therefore, we believe that our findings will also contribute to the targeted therapy efforts in other cancer types as well.

Keywords: PRMT5
cancer
neuroblastoma
Advisor: La Thangue, N
Humphrey, T
Imaging cerebrovascular health using 7T MRI

Magnetic resonance imaging is a valuable clinical tool for the visualization of intracranial vasculature. Without exposing patients to ionizing radiation or intravenous contrasts, it can provide multi-modal structural information about the shape, structure, and function of the various vessels involved in stroke and dementia. However, imaging methods are limited by the achieved contrasts and resolutions, as well as the required scan times.
Ultra-high field 7T MRI offers increased signal-to-noise ratio and desirable changes in relaxation parameters, therefore promising substantial improvements to existing neurovascular MRI approaches such as MR angiography (MRA) and MR vessel wall imaging (VWI). However, 7T MRI also introduces increased specific absorption rates and reduced homogeneity and extent of the transmit B1 field. Because of the latter, the first research chapter in this thesis (Chapter 3) studies the possibility to increase the extent of this 7T B1+ field into the feeding arteries in the neck using parallel transmission (pTx).
The second research chapter (Chapter 4) aims to improve the accelerated acquisition of high-resolution MRA using compressed sensing reconstruction. This facilitates the visualization of the small intracranial arteries which are involved in lacunar infarcts and vascular dementia, which can be achieved within clinical scan times.
The final parts of this thesis (Chapters 5-7) focus on a specific intracranial VWI sequence called DANTE-SPACE. A simulation framework for the sequence is first presented in Chapter 5. This framework includes various additional processes such as (pulsatile) tissue motion and B1+ variations to accurately represent the intra- and extra-vascular contrast mechanisms. The simulations are then used for the optimization and comparison of the T2-weighted DANTE-SPACE sequence at 3T, 7T without pTx, and 7T with pTx. The optimizations aim to maximize the contrast between both the blood within and the cerebrospinal fluid surrounding intracranial vessel walls, and the comparison between different field strengths provides a first quantitative indication of the added value of ultra- high field MRI for the DANTE-SPACE sequence.

Keywords: cerebrovascular imaging
DANTE-SPACE
ultra-high field MRI
MR angiography
compressed sensing
vessel wall imaging
Advisor: Jezzard, P
Hess, A
Sources and processes of per- and polyfluoroalkyl substances in snow and ice on Svalbard

Per- and polyfluoroalkyl substances (PFAS) are a group of persistent organic contaminants. Some are toxic and bioaccumulative, and pose a hazard to human and environmental health. This thesis aims to further understand the sources and environmental processes of PFAS in the Arctic terrestrial cryosphere. This was achieved by analysing PFAS in an ice core (spanning 2006 – 2019) from the remote Lomonosovfonna ice cap and surface snow samples collected seasonally (January – August 2019) on Svalbard (Norwegian Arctic). These samples were used to assess the levels, sources, and the significance of photochemical processes in the atmospheric transformations of PFAS. In addition, the extent of PFAS contamination from local sources in the settlement of Longyearbyen, Svalbard, was investigated. PFAS contamination is widespread in the remote Arctic, since more than 26 compounds were detected, including C2 – C11 perfluoroalkyl carboxylic acids (PFCAs), perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS). In the Lomonosovfonna ice core, PFCAs are thought to come from the atmospheric degradation of fluorotelomer alcohols (FTOHs) and chlorofluorocarbon (CFC) replacement products such as hydrofluorocarbons (HFCs). High levels of trifluoroacetic acid (TFA) contribute to 71% of C2 – C11 PFCAs in the ice core. Neither the ice core nor surface snow indicate that marine aerosols are a source of PFAS deposition in the Arctic. Hexafluoropropylene oxide dimer acid (HFPO-DA or GenX) and trifluoromethane sulfonic acid (TFMS) are widespread in surface snow, but the source of TFMS is unknown. During 24-hour daylight, the deposition fluxes of C2 – C11 PFCAs, PFHxS, PFOS and HFPO-DA (GenX) were 2 – 38 times higher in surface snow. Several PFCAs, PFOS and HFPO-DA are found to correlate with solar radiation which indicates that photochemical processes likely contribute to the atmospheric formation of these PFAS. Further investigation suggests that bromine radicals are a significant additional oxidant for the degradation of precursors (e.g. FTOHs, HFCs) in the atmosphere during Arctic Springtime.

Keywords: trifluoromethane sulfonic acid
PFAS
fluorotelomer alcohols
long-range transport
ice core
Svalbard
per- and polyfluoroalkyl substances
snowmelt
snow
hydrofluorocarbons
trifluoroacetic acid
Advisor: Robinson, S
Macias-Fauria, M
Cultured or encultured?: A study of the cultural identities of English teachers and the English department in secondary schools

This research explores the relationship between the identity of an English department in a secondary school and the individual teachers within that unit, and the ways in which the departmental identity interacts with that of the individual identity.  Although there is increasing pressure on all schools to perform within the competitive realm of league tables, schools’ reactions to these pressures vary. It is these variances and their effects on the cultural identities of English teachers and departments which the research investigates through case studies of three schools in the south of England. These case studies offer differing perspectives drawn from teachers with varied experience as teachers of English.
To facilitate an understanding of the process by which the departments interact with the individual identities, the qualitative data tools of semi-structured interviews, observations and documentary analysis were used. These tools provided data that illustrated both the department view and the individual view of identity.
Data was thematically analysed, initially through inductive coding where commonalities emerged. These commonalities were then synthesised to form a coding framework which was applied to deductive coding of the same data and across the data of the departments in two other schools. Findings suggest English teachers are diverse in their understanding of the role of an English teacher and the purpose of English teaching. Secondly, the construction of an English teacher’s identity is shaped by their past experiences, interactions with others and government and school wide policies and practices. The data indicated there are numerous external factors that influence the context in which teachers operate which can affect the individual’s identity. Finally, the study intimated that the culture of an English department is affected by external influences. The ways the department managed these varied due to the internal cultures of cooperation and a shared vision on the one hand and the top down imposition on the other. In both cases the departments’ responses impacted upon the identity of that individual.

Keywords: English departments
case studies
English teachers
identity
Advisor: Elliott, V
Thompson, I
Queering the queer: an exploration of how gay celibate asceticism can renew and inform the role of desire in contemporary Anglican theology

Being gay and celibate are together intensely queer realities. They are, however, curiously side- lined in queer and contemporary Anglican theology. This thesis explores gay celibate asceticism (GCA) as an essential witness in the contemporary Anglican discussion of human sexuality. Through a constructive theological analogy between holy virginity and GCA in Augustine’s theology of desire, I explain how it both differs from and is like holy virginity as an instantiation of peregrine oddity or queerness. This queerness uses creation in enjoyment of God and invents a new ‘category’ of erotic martyrdom which Augustine leaves space for in De Sancta Virginitate. Through Oliver O’Donovan’s theology of moral order, I proffer a theological basis for GCA as i) a Christ-like exclusion from the created good of marriage, and ii) a form of sacramental existence that, due to its exclusion, enjoys greater erotic intimacy and inclusion with Christ in his death and resurrection. By interrogating Christ’s prayer in the Markan Gethsemane, I retrieve Coakley’s trinitarian ascesis and argue that GCA is a ‘new asceticism’ which calls gay affectivity to a pneumatocentric, christological renewal. Finally, I examine Ward’s erotics of redemption, agreeing with his queer diagnosis of the Fall on gender and sexuality but differing on the solution he provides. Rather than suspending sexual difference through trinitarian analogy, gay celibates understand sexual difference as an essential part of created order in the manner of Augustine and O’Donovan. By revisiting Richard Hooker’s Lawes, GCA is described as a via media between innovationist accounts like Robert Song, Graham Ward, and Rowan Williams, and ascetical theologies like O’Donovan and Coakley.
The thesis argues that gay celibacy is a robustly Hookerian way forward from the Living in Love and Faith project. GCA needs to inform LLF in that it faces the theodicean and ethical dilemma of same-sex desire through scripture, reason, and a distinctly Augustinian erotics of redemption. Finally, I conclude that GCA queers the queer by synthesising queerness and holiness in a hope- filled and pneumatocentric/christological ascesis that affirms and relativizes the created order through Christ’s resurrection in the foretaste of the Spirit’s transformation of our bodies.

Keywords: Graham Ward
theology
gay
queer
celibacy
Richard Hooker
Oliver O'Donovan
Anglican
desire
Sarah Coakley
Augustine
queer theology
pastoral theology
ethics
queering
homosexuality
Advisor: Hordern, J
Genetically-predicted effects of LDL cholesterol lowering therapeutic targets on the risk of diabetes

Background: Statins, which lower circulating LDL-C by inhibiting HMG CoA reductase, are a first-line treatment for prevention of cardiovascular disease. Recent clinical and genetic studies have shown that statins modestly increase the risk of incident type 2 diabetes (T2DM). The biological mechanisms of statin-induced T2DM remain unknown. It also remains unclear if patients with risk factors for diabetes are at higher proportional risk of statin-induced T2DM than those without risk factors, as some studies have claimed. Evidence for the effect of another LDL-C lowering drug, ezetimibe, on T2DM is insufficient, but if related to LDL-C, it may also impact on T2DM risk.
Methods: HMGCR and NPC1L1 genetic risk scores (GRS) were used as statin and ezetimibe genetic proxies, respectively. The principles of a drug-target Mendelian randomisation were used to examine the effect of 1 SD (~1 mmol/L) lower genetically predicted LDL-C on T2DM, glycaemic traits and anthropometric measures in approximately 330,000 white British participants in UK Biobank. The heterogeneity of HMGCR GRS associations with T2DM and diabetes-related traits was also assessed in subgroup analyses among participants with varying susceptibilities (both genetic and clinical) to T2DM.
Results: 1 SD lower HMGCR-predicted LDL-C was associated with a 26% (95% CI 8%, 47%) higher risk of total T2DM, higher HbA1c (0.05 SD 95% CI 0.02, 0.08) and higher levels of adiposity. There was no evidence to support the hypothesis that the proportional effect of HMGCR GRS on T2DM in participants was greater in individuals with T2DM risk factors, and instead some subgroup analyses suggested a trend towards lower proportional risk of HMGCR-associated T2DM in those at higher risk of T2DM. NPC1L1 GRS showed a similar but non-significant association with T2DM per 1 SD lower genetically predicted LDL-C to that observed for HMGCR and a strong association with HbA1c (0.15 SD, 95% CI 0.09, 0.22) per 1 SD lower NPC1L1-predicted LDL-C.
Conclusions: An HMGCR GRS associated with lower LDL-C levels was associated with higher T2DM, HbA1c levels and measures of adiposity. Although most cases of T2DM occurred in participants at elevated risk of T2DM, there was no excess proportional risk of T2DM in this subgroup compared to participants at lower risk.
The association of NPC1L1 with T2DM was underpowered, but directionally consistent with the associations observed for HMGCR, and the NPC1L1 GRS was also associated with higher HbA1c levels but not with higher levels of adiposity.

Keywords: NPC1L1
mendelian randomisation
type 2 diabetes
statins
statin therapy
HMGCR
ezetimibe
Advisor: Hopewell, J
Parish, S
Preiss, D
The making of an American orchestra: U.C. Hill and the Philharmonic in New York, 1815-1848

As an institution, the symphony orchestra is rarely evaluated beyond the repertoire it performs and the number and talent of instrumentalists on stage. Yet, every community-based orchestra reflects the broader culture of the place and time in which it first began. Founded in 1842 as a musician-managed cooperative orchestra, the New York Philharmonic reflected the egalitarian ideals of popular democracy associated with Jacksonian America.
The driving force behind this new venture, also its first president and conductor, was the American-born violinist Ureli Corelli Hill (1805–1875). Critically important, Hill was the first American professional musician to travel abroad. Between 1835-1837 he studied with Louis Spohr in Kassel, played in Felix Mendelssohn’s orchestra at the premiere of his Paulus in Düsseldorf, and was hired as third viola in London’s Drury Lane Theatre orchestra. While on this journey, Hill kept a diary, currently unpublished and the inspiration for this study, that captured his reactions to Old World culture along with comparisons to New York.
In addition to deciphering the opinions, politics, and worldview of Hill, for the first time this study provides a more granular accounting of the lives of early nineteenth century working musicians, something that has been recognized as lacking in the literature (Crawford and Root). Through Hill’s experiences, the focus shifts to the musicians, mostly instrumentalists, who formed a distinct musical culture and a close-knit, mutually supportive community in New York City between 1815 and 1848. Along with Hill, many of these men had been involved with earlier musical institutions in the City: the 1824 New York Philharmonic, the García Opera Company orchestra that introduced Italian opera to the United States, the New York Sacred Music Society, and the New York Musical Fund Society. Their shared experiences as New York City became the cultural capital of the country, combined with the ideals of popular democracy, made the New York Philharmonic a uniquely American symphony orchestra.

Keywords: orchestra conductor
Malibran
American musician abroad
Beethoven Symphony No. 9
Italian opera
London musicians 1830s
Mendelssohn St. Paul
suffrage
popular democracy
Jacksonian America
George 'Yankee' Hill
Drury Lane Theatre
New York Philharmonic
Manuel Garcia
Louis Spohr
Ureli Corelli Hill
Felix Mendelssohn
egalitarian ideals
American Psalmody
Advisor: Burden, M
Protein promise? Application of mass spectrometry-based proteomics techniques to identify cerebrospinal fluid biomarkers for diagnosing suspected central nervous system infections - a focus on Japanese encephalitis virus infection

Neurological infections account for considerable death and disability worldwide. Even in the best-resourced settings, existing diagnostic tests are inadequate and adversely affect patient outcomes. In this thesis, I propose that the identification of host biomarkers of neurological infection could fill the gap in case ascertainment.
In Laos, as is the case in other countries in Asia, the leading cause of neurological infection is Japanese encephalitis virus (JEV). Specifically for Japanese encephalitis (JE), the pathogen is present at very low levels such that it is rarely detected in any body fluid, and the mainstay of diagnosis is anti-JEV IgM antibody capture enzyme-linked immunosorbent assay. This has poor specificity. Furthermore, there is no rapid diagnostic test to be used in the rural areas that JEV exists. JE represents an important neurological infection to illustrate the potential role of host protein biomarkers for diagnosis.
I retrospectively tested a cohort of 163 patients recruited as part of the Laos central nervous system (CNS) infection study. Application of liquid chromatography and tandem mass spectrometry (LC-MS/MS), using extensive offline fractionation and tandem mass tag labelling, enabled a comparison of the CSF proteome in 68 JE patient vs 95 non-JE neurological infections. 5,069 proteins were identified, including 4,805 human proteins and 265 pathogen proteins. I incorporated univariate analysis of differential protein expression, network analysis and machine learning techniques to build a ten-protein diagnostic signature of JE.
Pathways related to JE infection included neuronal damage, anti-apoptosis, heat shock and unfolded protein responses, cell adhesion, macrophage and dendritic cell activation as well as a reduced acute inflammatory response, hepatotoxicity, activation of coagulation, extracellular matrix and actin regulation. I verified the results by performing DIA LC-MS/MS in 16 (10%) of the samples, demonstrating 82% accuracy using the same model. Ultimately, antibody-based validation will be required, in a larger group of patients, in different locations and in field settings, to refine the list to 2-3 proteins that could be harnessed in a rapid diagnostic test.

Keywords: mass spectrometry
biomarkers
proteomics
meningoencephalitis
Japanese encephalitis
encephalitis
flavivirus
neurological infections
Asia
central nervous system infections
Advisor: Zitzmann, N
Newton, P
Dubot-Pérès, A