Understanding the experience of ‘brain fog’ in coeliac disease: an interpretative phenomenological analysis

This thesis is submitted by Emily May Ahmed in partial fulfilment of the degree of Doctor of Clinical Psychology at the University of Birmingham. The thesis is comprised of three chapters. The first chapter is a meta-analysis which aims to provide a current prevalence estimate of depression in adults with coeliac disease, including evaluation of risk of bias factors. Additionally, it includes a brief secondary analysis, within the appendix, describing prevalence and relative risk estimates for other mental health disorders associated with coeliac disease. The second chapter is a qualitative empirical study which uses interpretative phenomenological analysis (IPA) methodology to explore the complex lived experiences of one of the lesser-known symptoms associated with coeliac disease – ‘brain fog’, in seven participants. Both the meta-analysis and empirical studies have clear clinical implications for the cognitive and psychological support that individuals with coeliac disease should be offered during and after diagnosis. Finally, the third chapter is comprised of two press release documents, which provides an accessible summary of the main findings of both the meta-analysis and the empirical research study

John Donne and music

This thesis explores John Donne’s engagement with music through his life, writing and the setting of his lyrics to music. It argues that Donne was more involved with music than previously thought. Donne’s encounter with music appears to have begun at a young age, fostered at home, nurtured through relationships (family, friends, patrons, peers) and shaped by experiences (listening to music, playing music, and commissioning music when Dean of St. Paul’s). Examples of musical references and figurative language in Donne’s poetry and prose reveal a musically trained mind. Donne’s social and professional connections with the foremost composers and musicians of his time establish his association with key figures in early modern English musical culture. My analysis of the surviving repertoire of seventeenth-century musical settings of Donne’s poetry explores the relationship of those settings to literary and musical genres, and to broader social and cultural contexts in early modern England and Europe. Significant changes in musical style and literary taste in the culture of the period are reflected in the different ways in which Donne’s poems were set to music. The musical settings of Donne’s poetry also show how characteristic features of his verse – rhythmical, thematic, and imagistic counterpoint and even discord – are refashioned and re-presented in musical performance. The considerable number of Donne’s poems that were set to music by composers evince the impact his lyric poetry had on the musical culture of the early to mid-seventeenth century. Based on manuscript and printed evidence, I argue that Donne’s affinity for music is most evident in those of his lyric poems titled, in manuscript and print, as ‘Songes’ or ‘Songs’, melodic lyrics that were meant to be sung as well as read. By situating this group of poems in the context of early seventeenth century English musical culture and performance, this thesis prompts us to re-evaluate our reading of Donne’s ‘Songes/Songs,’ our view of Donne’s engagement with musical culture, and indeed of his musicality

Resolving the liver sinusoidal endothelial phenotype in health and disease

The burden of liver disease is continuously increasing globally, and this emphasises the need for the development of therapeutics. In order for this to be achieved, potential cellular and molecular targets need to be identified. Liver sinusoidal endothelial cells (LSECs) play a key role in maintaining liver homeostasis and their dysfunction drives liver disease pathophysiology and this role needs to be further elucidated. In order to identify phenotypic differences in LSECs in health and disease, a combination of analytical techniques such as immunohistochemistry and qPCR was applied on human tissue specimens. To confirm whether these changes are recapitulated in vitro, I isolated LSECs from human healthy and cirrhotic tissue specimens for the establishment of culture model of human LSECs. Validation of functional and phenotypic characteristics of LSECs in vitro was carried out using immunocytochemistry and qPCR. Furthermore, the development and optimisation of a super-resolution imaging protocol for the visualisation of LSEC fenestrations was performed. Altered expression and downregulation of scavenger receptors in LSECs was identified in diseased human tissue specimens compared to healthy specimens and this confirmed capillarisation of sinusoidal endothelial cells in liver disease. Expression of scavenger receptors and key regulatory molecules was maintained in LSECs in vitro. The phenotypic changes in LSECs identified in liver tissue specimens were partially recapitulated in LSECs in vitro. The application of pharmaceutical molecules for the enhancement of nitric oxide (NO) signalling in LSECs revealed an altered genotype in healthy and cirrhotic LSECs. Finally, fenestrations were visualised on the LSEC membrane using the developed super-resolution imaging protocol and improvement in LSEC porosity following the application of sildenafil citrate. Hence these findings emphasise the relevance of appropriate culture models and imaging approaches to study phenotypic changes in LSECs in relation to disease and highlight the therapeutic potential of sildenafil citrate in improving LSECs porosity

Place, pollution and public health: municipal responses for sanitation in Birmingham 1840s-1920s

This thesis explores the municipal responses to poor sanitation and river pollution in Birmingham between the 1840s and the 1920s. It assesses the impact and effectiveness of those responses on the health of England’s second largest city and re-examines the contemporary view of the city’s governance and the alleged association of sanitation reform and ‘municipal socialism’ linked to one of the city’s political figures, Joseph Chamberlain. This history of sanitation, set within its political, social and economic contexts, examines the development of utilities for water supply and sewage treatment in Birmingham and offers the first thorough academic analysis of the broader municipal policy towards public health in the city during that period. It also explores the development of municipal systems and public health administration, as well as medical theory and practice, and is therefore a history of the urban environment that overlaps with the social history of medicine. To examine the interrelationship and importance of place, people and policy this study adopts a microhistorical approach to appraise a single local authority, particular committees, specialised roles and individuals. Attention is given not only to those who governed, but also to people who worked within those systems. Close analysis of place-specific primary sources, some never used before and produced by those involved, has facilitated a fuller contextualisation of municipal responses and reveals the nature and effectiveness of local government systems dealing with public health. The research findings reveal not a sanitary revolution but rather a lengthy foundational period of local government development and investment in sanitary infrastructure before Birmingham had the capability to address poor sanitation for all citizens. While this foundational period did not have an immediate positive impact on the health of the city’s poorest between 1870 and 1904, it nevertheless throws new light on the living conditions in the courts of back-to-back housing and adds significantly to an understanding of the impact of waste management systems. This challenges the image of Birmingham closely linked to Chamberlain and his impact on sanitation and municipal socialism in the 1870s and 1880s; an image this thesis argues is far from justified. The findings can feed into debates surrounding urban sanitation, infrastructure investment and its effects on mortality, and underscores the importance of place-specific contextualisation. The impact of Birmingham’s first two Medical Officers of Health is also considered within place-specific, medical and contemporary understandings of disease contexts, with a reassessment of their impact on infant mortality in the city. This thesis adds significantly to an understanding of Birmingham’s municipal history and extends the historiography for the beginnings of the water industry in England and Wales and the history of public health in Britain

Investigating the role of complement in the pathogenesis of pre-eclampsia in previously healthy pregnant women, and in high-risk groups.

Pre-eclampsia (PE) is a leading cause of obstetric morbidity and mortality. Certain groups of women, including those with chronic kidney disease (CKD) and those of sub-Saharan African (SSA) ethnicity, are at particularly high risk. There remains no definitive treatment other than expedited delivery of baby and placenta. Previous studies suggest a role for complement dysregulation in the pathogenesis of PE, but results are often conflicting, and it remains unclear whether changes in circulating complement concentrations reflect a general heightened inflammatory state in PE or are directly associated with placental complement-mediated injury. This thesis tested the hypothesis that PE is associated with excessive complement activation within placental tissue, with concurrent complement activation within the maternal and fetal circulation, and that groups with a high prevalence of PE, and of PE with severe features (women with CKD and women of SSA ethnicity) would exhibit a greater degree of systemic complement activation. Three arms of research were conducted, and I report: • In a cohort of previously healthy women, PE was associated with significant placental complement deposition, associated with concurrent changes in maternal and fetal circulating complement markers (reduced maternal properdin and C4, and elevated maternal and fetal Ba). Placental C4d deposition was strongly correlated with maternal properdin and C4, suggesting that those patients with the most excessive changes in circulating markers of complement activation also have the greatest extent of placental complement-mediated damage. • There was no evidence of excessive complement activation in the maternal circulation in superimposed PE in a cohort of women with CKD. However, raised Ba levels were associated with adverse pregnancy outcomes in women with CKD. • There was no evidence of excessive complement activation in PE in a Ghanaian cohort of women of SSA ethnicity when compared to healthy pregnant controls. However, pregnant women of SSA ethnicity did have significantly elevated levels of C5b-9, serum free light chains, and immunoglobulin G, when compared to the UK-recruited cohorts; suggestive of a baseline elevated inflammatory state. The results suggest that inhibition of complement activation is a potential therapeutic target for certain groups of women with PE. However, PE is a heterogenous syndrome and additional pathophysiological mechanisms may contribute to the development of disease in women with CKD and women of SSA ethnicity

Demystifying emotion-processing: autism, alexithymia, and the underlying psychological mechanisms

Despite extensive research, the mechanisms underpinning successful emotion recognition remain unclear. Constructionist, template-matching, and signal detection theories illuminate several emotion-related psychological processes that may be involved – namely the conceptualisation, experience, visual representation, and production of emotion – however, this requires empirical verification. Therefore, across the six empirical chapters described here, I developed and applied several novel experimental paradigms to assess the way in which individuals conceptualise, experience, visualise, produce and recognise emotion, and created new mathematically plausible, mechanistic models that shed light on the processes involved in emotion recognition. In doing so, I identified several candidate mechanisms that may underpin the emotion recognition difficulties seen in a range of clinical conditions, including autism spectrum disorder, and I (1) determined whether there are differences between autistic and non- autistic individuals in these emotion-related psychological processes, and (2) ascertained whether differences therein underpin emotion recognition challenges for autistic people. Ten years ago, it was theorised that the emotion-related difficulties of autistic individuals do not stem from autism per se, but rather alexithymia – a subclinical condition highly prevalent in the autistic population characterised by difficulties identifying and describing emotions. Since its inception, this theory has gained empirical support, with multiple studies documenting that alexithymia, and not autism, is associated with emotion- processing differences. However, to date, this evidence has largely been confined to the domain of emotion recognition. As such, it is unclear whether there are differences between autistic and non-autistic individuals in the conceptualisation, experience, visual representation, and production of emotion, after controlling for alexithymia. Here, I resolved this ambiguity, discerning the explanatory scope of the “alexithymia hypothesis”: there were no differences between autistic and non-autistic individuals in the understanding or differentiation of emotion concepts (Chapter 6), the precision or differentiation of emotional experiences (Chapter 6), and the speed (Chapter 3) or differentiation of visual emotion representations (Chapter 5), after controlling for alexithymia. Nevertheless, there were differences between groups with respect to the precision of visual representations (Chapter 5), the production of emotional facial expressions (Chapter 7), and recognition of specific emotions (Chapter 2), even after accounting for this confound. Despite suggestions that autistic individuals adopt alternative strategies to recognise the emotions of others, very few studies have examined mechanistic differences in emotion recognition between autistic and non-autistic people. Therefore, here I aimed to compare the processes involved in emotion recognition for these groups. Across multiple empirical chapters, I identified that there are similarities and differences in the processes implicated in emotion recognition for autistic and non-autistic people (Chapters 4, 5, 6, and 7), with autistic individuals relying on fewer emotion-related psychological processes. By elucidating several candidate mechanisms underpinning superior emotion recognition, my doctoral work paves the way for future supportive interventions to help both autistic and non-autistic individuals to accurately interpret other people’s emotions, thus ultimately fostering more successful and fluid social interactions

'A Hand Up, Not a Hand-Out', New Labour and Street Homelessness 1997-2010

This research examines the impact of the New Labour government on street homelessness across their three terms of office from 1997 to 2010. Grounded in the oral testimonies of those who designed and delivered New Labour’s homelessness policies, it concludes that Labour’s achievements in reducing street homelessness were real and significant. Challenging interpretations of New Labour’s interventions as ‘revanchist’ in intent, it shows instead that Labour enacted a coherent and sustained programme, driven from the centre of government, that focused on developing long-term solutions to rough sleeping. It shows that Labour utilised novel and innovative methods of governance to reduce the high levels of rough sleeping it inherited on attaining office, devised new methods of addressing homeless prevention, and instituted policies designed to empower former rough sleepers to permanently escape homelessness. To achieve its aims, New Labour facilitated significant improvements in the scale, scope and working practices of the voluntary sector homeless agencies that delivered its programme. This research also shows that New Labour’s homelessness policies were enacted in accord with its stated ‘Third Way’ ideology. Given the efficacy of its street homelessness programme, it argues that the Third Way deserves more serious attention than it is commonly afforded, both as an ideology and a mechanism of governance. In addition, as Labour’s commitment to addressing street homelessness was sustained long after press and public interest had declined, this research challenges a common characterisation of New Labour as being primarily concerned with maintaining a positive public image at the expense of delivering on social policy objectives. By focussing on the mechanisms of government and the processes employed in the delivery of Labour’s homelessness policies, this research also offers a broader challenge to the writing of political history. Arguing that the process of transferring rhetoric into policy, and policy aims into actual improvements in the quality of citizens lives, is perhaps the most important task of government, it calls for a greater prominence to be given to delivery of social policy aims in assessments of governments’ performance in office and in the writing of political histories

Individual differences affecting the bilingual language switching abilities

Language switching is bilinguals’ ability to change swiftly between languages, so that the communicative message is understood by its recipients. However, the exact cognitive and neural mechanism of language switching has not been fully understood yet, and it is not clear why some bilinguals are better at switching into the required language than others. To answer these questions, the current thesis investigated the cognitive and neural processes that underlie language switching, as well as the individual differences that affect it. We first devised and tested a new questionnaire measure of bilingual switching experiences and interactional environments. The results showed a factorial structure that corresponded well with two crucial bilingual experience and cognitive control theories, the Adaptive Control Hypothesis (Green & Abutalebi, 2013) and the Unified Bilingual Experience Trajectory Model (DeLuca et al, 2020). We also measured behaviourally and electrophysiologically how language control is applied during language switching, aiming to explore when and where language switching costs, marking switching inefficiency, appear. The results demonstrated a complex landscape of brain functioning processes, where different levels of language control overlapped and ran in parallel, and were further affected by the specific language bilinguals needed to select. These findings complied with a domain-general cognition account of language switching, where inhibition is involved. Investigating further the involvement of domain-general inhibitory control in language control, we tested for any relationships between the two in language switching and domain-general control tasks but found only very partial qualitative overlap in bilinguals’ neural responses. Finally, we tested the relationships of the behavioural and neural markers of language switching with the individual differences factors of language switching and bilingual experience from our questionnaire measure. The results partially supported the claim that different bilingual experiences could affect language switching on neural level through executive control training. To conclude, this thesis offers an investigation of bilinguals’ language control, with a wide range of behavioural, neural and experiential measures, from the same bilingual sample. The findings support the idea that language control is a complex non-linear process that could be explained to some degree by bilingual individual differences factors and to some degree by domain-general inhibitory control. АБСТРАКТ Превключването между езиците е способността на двуезичните хора да преминават бързо между езиците, така че комуникативното послание да бъде разбрано от адресатите. Въпреки това, точният когнитивен и невронален механизъм на езиковото превключване все още не е напълно изяснен, и не е ясно защо някои двуезични хора са по-добри в превключването към нужния език от други. За да отговорим на тези въпроси, настоящата дисертация изследва когнитивните и невронални процеси, лежащи в основата на превключването между езиците, както и индивидуалните различия, които му влияят. Най-напред създадохме и тествахме нов въпросник за опита на двуезичните хора с превключването между езиците и средите им на общуване. Резултатите показаха факторна структура, която съответства в голяма степен на две основни теории за двуезичния опит и когнитивния контрол - Хипотезата за адаптивния контрол (Green & Abutalebi, 2013) и Обединения модел за траекторията на двуезичния опит (DeLuca et al., 2020). Също така, измерихме поведенчески и електрофизиологично как се прилага езиковият контрол при превключването между езиците, с цел да изследваме кога и къде се проявяват разходите при това превключване, които демонстрират неефективността на превключването. Резултатите показаха сложна картина от мозъчни функционални процеси, където различните нива на езиков контрол се припокриват и изпълняват паралелно, допълнително повлияни от конкретния език, който двуезичните лица трябва да изберат. Тези резултати съответстват нa интерпретацията на езиковото превключване чрез генералната неспецифична когниция, която включва и инхибирането. Изследвайки по-задълбочено участието на генералния неспецифичен инхибиторен контрол в езиковия контрол, тествахме връзката между двата в задачи за превключване между езиците и генерален неспецифичен контрол, но открихме само много частично качествено припокриване в невроналните процеси на двуезичните ни изследвани лица. За финал, тествахме и връзките между поведенческите и невронални маркери на езиковото пречключване и факторите от въпросника ни за индивидуалните различия в превключването между езиците и двуезичния опит. Резултатите частично подкрепиха твърдението, че разнообразният двуезичен опит може да повлияе на езиковото превключване на невронално ниво чрез тренирането на когнитивния контрол. В заключение, тази дисертация представя изследване на езиковия контрол на двуезични лица, съдържащо широка гама от поведенчески, невронални и свързани с опита променливи, събрани от една и съща двуезична експериментална извадка. Резултатите подкрепят идеята, че езиковият контрол е сложен нелинеен процес, който може да бъде обяснен отчасти от двуезичните индивидуални различия и отчасти от генералния неспецифичен инхибиторен контрол. RESUMEN La alternancia de idiomas es la habilidad de los bilingües de cambiar rápidamente de un idioma a otro, para que el mensaje comunicativo sea entendido por sus receptores. Sin embargo, el mecanismo cognitivo y neuronal exacto de la alternancia de idiomas aún no se comprende completamente, y no está claro por qué algunos bilingües son mejores que otros al cambiar al idioma requerido. Para responder a estas preguntas, la presente tesis investigó los procesos cognitivos y neuronales que subyacen a la alternancia de idiomas, así como las diferencias individuales que lo afectan. Primero, creamos y sometimos a prueba un nuevo cuestionario para medir las experiencias de la alternancia de idiomas y los entornos de interacción de los bilingües. Los resultados mostraron una estructura factorial que se correspondía bien con dos teorías importantes sobre la experiencia bilingüe y el control cognitivo: la Hipótesis del Control Adaptativo (Green & Abutalebi, 2013) y el Modelo Unificado de la Trayectoria de Experiencia Bilingüe (DeLuca et al., 2020). También medimos de manera conductual y electrofisiológica cómo se aplica el control del lenguaje durante la alternancia de idiomas, con el objetivo de explorar cuándo y dónde aparecen los costos cognitivos de esta alternancia, que serían un indicador de ineficiencia en el proceso. Los resultados revelaron un escenario complejo de procesos de funcionamiento cerebral, donde diferentes niveles de control del lenguaje se superpusieron y se ejecutaron en paralelo, y se vieron afectados aún más por el idioma específico que los bilingües necesitan seleccionar. Estos hallazgos concuerdan con una explicación cognitiva de dominio general del cambio de idioma, en la cual está involucrada la inhibición cognitiva. Al investigar en profundidad la participación del control inhibitorio de dominio general en el control del lenguaje, evaluamos relaciones entre ambos, en tareas de alternancia de idiomas y de control de dominio general, pero sólo se encontró una superposición parcial cualitativa en las respuestas neurales de los bilingües. Finalmente, estudiamos las relaciones entre los marcadores conductuales y neuronales de la alternancia de idiomas, junto con los factores de diferencias individuales en este proceso y la experiencia bilingüe obtenida en nuestro nuevo cuestionario. Los resultados respaldaron la afirmación de que a través del entrenamiento del control ejecutivo, las experiencias bilingües podrían afectar el cambio de idioma a nivel neuronal. En conclusión, esta tesis ofrece una investigación sobre el control del lenguaje de los bilingües, con una amplia gama de medidas conductuales, neuronales y experienciales, a partir de una misma muestra bilingüe. Los hallazgos respaldan la idea de que el control del lenguaje es un proceso complejo y no lineal, que puede explicarse en cierta medida por los factores de las diferencias individuales de los bilingües y en cierta medida por el control inhibitorio de dominio general

The pseudo-Oecumenian catena on Ephesians: text, translation, and commentary

This thesis seeks to advance the understanding of the production and purpose of the Ps. Oecumenian catena on Ephesians through the creation of a critical edition, its translation, and theological commentary. The edition is created through the full transcription and collation of seventeen catena manuscripts, drawn from all known catena manuscripts containing the Ps.-Oecumenian catena on Ephesians. The selected manuscripts were chosen on the basis of a test passage applied to all manuscript witnesses of this catenae tradition and they represent three of the main catena types established by Karl Staab and indicative of the development of the catena from its earliest recoverable period containing the Urkatena and Corpus Extravagantium to the addition of the Scholia Photiana. An analysis of the seventeen manuscripts selected for the edition is provided alongside a stemma codicum representing a conceptualisation of textual relationships between the manuscripts and the process of the transmission of the catena. The presence of author attributions in the manuscript tradition and the source material of unattributed scholia are examined with discussions related to their reliability. The identification of Oecumenius as a source for select scholia within the catena is paralleled with similar material in the commentary on the Apocalypse produced by Oecumenius, concluding that the same source is likely responsible for both. The editorial text of the critical edition is presented alongside its English translation with an accompanying theological commentary. The commentary analyses the content of each scholion in light of patristic exegesis from the second to seventh centuries. A critical edition with apparatus is provided for the entire catena of Ephesians with a separate edition and apparatus, with English translation, included for the Scholia Photiana

Social and non-social reasoning in relation to autism and autistic traits

Four experiments examined reasoning and decision-making tendencies across social and non-social domains in relation to autism and autistic traits in adults. Experiments were created to measure forced-choice judgments and written justifications in a comparison paradigm of social and non-social scenario-based domains. Three experiments used a scenario-based task to measure moral reasoning, while one experiment focused specifically on causal reasoning with a task following a common cause network structure. Dual Process Theories propose a distinction between two types of information processing: intuition and deliberation. Intuition represents a quicker and more automatic process, while deliberation represents a slower and more effortful process. Following this notion, the Dual Process Theory of Autism suggests a tendency of greater deliberation and less intuition in decision-making and reasoning among autistic people and those with high autistic traits. To test this hypothesis across domains to see whether these tendencies are domain-specific or domain-general, three experiments (Experiment 1, 2, and 4) recruited participants from the general population and measured their levels of autistic traits. One experiment (Experiment 3) recruited autistic and well-matched non-autistic participants for a between group comparison. Experiment 1 found a relationship between higher autistic traits and a greater reliance on deliberation for forced-choice moral judgments within the social domain, and not the non-social domain. However, Experiment 2, using a modified version of the same task, did not reveal such a relationship, which was supported with participants’ written justifications. Experiment 3 used the first version of the same task and found no meaningful differences between autistic and matched non-autistic people in their moral judgments. Experiment 3 revealed subjective yet not objective differences between groups in their reasoning and decision-making, suggesting a subjective preference for and performance in reduced intuition among autistic people. Finally, Experiment 4 revealed no substantial differences in levels of autistic traits between participants, clustered as decisive and indecisive reasoners, based on their reasoning tendencies. Consistently, across all experiments, a distinction between social and non-social domains in terms of reasoning and decision-making was found. Taken together, this thesis suggests that there is strong evidence for a distinction between social and non-social domains in reasoning and decision-making. However, this thesis does not provide strong evidence for a greater deliberation and less intuition associated with a diagnosis of autism or high autistic traits. Nevertheless, mismatch between subjective and objective reasoning and decision-making among autistic people might suggest meta-cognitive differences to non-autistic people, rather than a difference in reasoning and decision-making