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The Epidemiology and Genetic Architecture of Vitamin D Deficiency in African Children
Vitamin D deficiency is a common public health problem worldwide. However, little is known about the epidemiology of vitamin D deficiency in Africa. In this thesis, I aimed to determine: 1) the prevalence of and risk factors associated with vitamin D deficiency in studies conducted in Africa; 2) the prevalence and predictors of vitamin D deficiency in African children; 3) the association between vitamin D and iron deficiency in African children; and 4) genetic variants that influence vitamin D status in Africans.
In a systematic review and meta-analyses of previous vitamin D studies in Africa, the average prevalence of low vitamin D status was 18.5%, 34.2% and 59.5% using cut-offs of 25-hydroxyvitamin D (25(OH)D) levels of <30 nmol/L, <50 nmol/L and <75 nmol/L, respectively. Populations at risk of vitamin D deficiency included newborns, women, and people living in high latitudes or urban areas.
In an epidemiological study of young children living in Africa, the prevalence of low vitamin D status was 0.6%, 7.8% and 44.5% using cut-offs of 25(OH)D levels of GC2 variant of the group-specific component (GC) gene, which encodes vitamin D binding protein.
Vitamin D deficiency was also associated with 80% higher odds of iron deficiency in these children. Adjusted regression models revealed that vitamin D deficiency was associated with higher ferritin and hepcidin levels suggesting lower iron status, and reduced sTfR and transferrin levels and increased TSAT and serum iron levels suggesting improved iron status.
Genome-wide association study (GWAS) in Africans revealed genetic variants that influence vitamin D status in vitamin D metabolism genes: DHCR7/NADSYN1, CYP2R1 and GC. However, the majority of SNPs from previous European GWASs did not replicate in the current GWAS.
Findings from this thesis indicate that vitamin D deficiency is prevalent in many African populations and should be considered in public health strategies in Africa
The Genetics of Pain: An exploration of gene-by-environment interactions and their effects on pain
The findings presented in this dissertation are part of the bigger SYMBIOME project which aims to use the biopsychosocial model of pain to develop a prognostic clinical phenotype for people that experience musculoskeletal (MSK) trauma. Chapter 2 presents an exploratory analysis to assess the relationships between genetic polymorphisms and pain severity and interference. Early childhood trauma was also explored as a moderator between genetic polymorphisms and pain outcomes. For pain severity, major allele carriers (A/A and G/A) of FKBP5 rs9394314 reported significantly higher scores than minor allele carriers (G/G). Further, major allele carriers who had at least one adverse childhood experience (ACE) reported significantly higher scores than minor allele carriers with at least one ACE. For pain interference, minor allele carriers (G/G) of CNR2 rs2501431 scored significantly higher than major allele carriers (A/A and G/A). Chapter 3 presents a cluster analysis that combines genotypes of FKBP5 rs9394314 and CNR2 rs2501431 to explore meaningful relationships with pain and trauma-related distress. ACE was also explored as a moderator of these relationships. Three clusters were identified where the second cluster characterized by major allele carriers of rs9394314 and minor allele carriers of rs2501431 reported significantly higher pain-related functional interference scores. Participants in the second cluster with at least one ACE reported higher pain interference and traumatic distress scores compared to the third cluster, while participants in the first cluster with at least one ACE reported higher pain severity compared to the first cluster. Chapter 4 presents genomic structural equation models (SEM) that explore the relationships of genotypes with trauma-related distress using the traumatic injuries distress scale (TIDS), ACE, and recovery outcomes. The results demonstrate a relationship between TIDS and recovery outcomes, and an indirect relationship between FKBP5 rs9394314 and recovery outcomes exist which is mediated by TIDS. Major allele carriers of FKBP5 rs9394314 reported higher TIDS scores, which was also demonstrated for participants that had at least one ACE. Major allele carriers that scored higher on the TIDS were predicted to be in the none-recovered category. These results support the notion that gene-x-environment interactions may play an important role in pain and recovery
Metaphors of London fog, smoke and mist in Victorian and Edwardian Art and Literature
Julian Wolfreys has argued that after 1850 writers employed stock images of the city without allowing them to transform their texts. This thesis argues, on the contrary, that metaphorical uses of London fog were complex and subtle during the Victorian and Edwardian periods, at least until 1914. Fog represented, in particular, formlessness and the dissolution of boundaries. Examining the idea of fog in literature, verse, newspaper accounts and journal articles, as well as in the visual arts, as part of a common discourse about London and the state of its inhabitants, this thesis charts how the metaphorical appropriation of this idea changed over time. Four of Dickens's novels are used to track his use of fog as part of a discourse of the natural and unnatural in individual and society, identifying it with London in progressively more negative terms. Visual representations of fog by Constable, Turner, Whistler, Monet, Markino, O'Connor, Roberts and Wyllie and Coburn showed an increasing readiness to engage with this discourse. Social tensions in the city in the 1880s were articulated in art as well as in fiction. Authors like Hay and Barr showed the destruction of London by its fog because of its inhabitants' supposed degeneracy. As the social threat receded, apocalyptic scenarios gave way to a more optimistic view in the work of Owen and others. Henry James used fog as a metaphorical representation of the boundaries of gendered behaviour in public, and the problems faced by women who crossed them. The dissertation also examines fog and individual transgression, in novels and short stories by Lowndes, Stevenson, Conan Doyle and Joseph Conrad. After 1914, fog was no more than a crude signifier of Victorian London in literature, film and, later, television, deployed as a cliche instead of the subtle metaphorical idea discussed in this thesis
Epigenetics : a catalyst of plant immunity against pathogens
The plant immune system protects against pests and diseases. The recognition of stress-related molecular patterns triggers localised immune responses, which are often followed by longer-lasting systemic priming and/or up-regulation of defences. In some cases, this induced resistance (IR) can be transmitted to following generations. Such transgenerational IR is gradually reversed in the absence of stress at a rate that is proportional to the severity of disease experienced in previous generations. This review outlines the mechanisms by which epigenetic responses to pathogen infection shape the plant immune system across expanding time scales. We review the cis- and trans-acting mechanisms by which stress-inducible epigenetic changes at transposable elements (TEs) regulate genome-wide defence gene expression and draw particular attention to one regulatory model that is supported by recent evidence about the function of AGO1 and H2A.Z in transcriptional control of defence genes. Additionally, we explore how stress-induced mobilisation of epigenetically controlled TEs acts as a catalyst of Darwinian evolution by generating (epi)genetic diversity at environmentally responsive genes. This raises questions about the long-term evolutionary consequences of stress-induced diversification of the plant immune system in relation to the long-held dichotomy between Darwinian and Lamarckian evolution
Supernatural crossing in Republican Chinese fiction, 1920sâ1940s
This dissertation studies supernatural narratives in Chinese fiction from the mid-1920s to the 1940s. The literary works present phenomena or elements that are or appear to be supernatural, many of which remain marginal or overlooked in Sinophone and Anglophone academia. These sources are situated in the May Fourth/New Culture ideological context, where supernatural narratives had to make way for the progressive intellectualsâ literary realism and their allegorical application of supernatural motifs. In the face of realism, supernatural narratives paled, dismissed as impractical fantasies that distract one from facing and tackling real life.
Nevertheless, I argue that the supernatural narratives do not probe into another mystical dimension that might co-exist alongside the empirical world. Rather, they imagine various cases of the charactersâ crossing to voice their discontent with contemporary society or to reflect on the notion of reality. âCrossingâ relates to charactersâ acts or processes of trespassing the boundary that separates the supernatural from the conventional natural world, thus entailing encounters and interaction between the natural and the supernatural. The dissertation examines how crossing, as a narrative device, disturbs accustomed and mundane situations, releases hidden tensions, and discloses repressed truths in Republican fiction.
There are five types of crossing in the supernatural narratives.
Type 1 is the crossing into âhauntedâ houses. This includes (intangible) human agency crossing into domestic spaces and revealing secrets and truths concealed by the scary, feigned âhauntingâ, thus exposing the hidden evil and the other house occupiersâ silenced, suffocated state.
Type 2 is men crossing into female ghostsâ apparitional residences. The female ghosts allude to heart-breaking, traumatic experiences in socio-historical reality, evoking sympathetic concern for suffering individuals who are caught in social upheavals.
Type 3 is the crossing from reality into the charactersâ delusional/hallucinatory realities. While they physically remain in the empirical world, the charactersâ abnormal perceptions lead them to exclusive, delirious, and quasi-supernatural experiences of reality. Their crossings blur the concrete boundaries between the real and the unreal on the mental level: their abnormal perceptions construct a significant, meaningful reality for them, which may be as real as the commonly regarded objective reality.
Type 4 is the crossing into the netherworld modelled on the real world in the authorsâ observation and bears a spectrum of satirised objects of the Republican society.
The last type is immortal visitors crossing into the human world. This type satirises humanityâs vices and destructive potential.
The primary sources demonstrate their writersâ witty passion to play with super--natural notions and imagery (such as ghosts, demons, and immortals) and stitch them into vivid, engaging scenes using techniques such as the gothic, the grotesque, and the satirical, in order to evoke sentiments such as terror, horror, disgust, dis--orientation, or awe, all in service of their insights into realist issues. The works also creatively tailor traditional Chinese modes and motifs, which exemplifies the revival of Republican interest in traditional cultural heritage. The supernatural narratives may amaze or disturb the reader at first, but what is more shocking, unpleasantly nudging, or thought-provoking is the problematic society and peopleâs lives that the supernatural (misunderstandings) eventually reveals. They present a more compre--hensive treatment of reality than Republican literature with its revolutionary consciousness surrounding class struggle. The critical perspectives of the supernatural narratives include domestic space, unacknowledged history and marginal individuals, abnormal mentality, and pervasive weaknesses in humanity.
The crossing and supernatural narratives function as a means of better understanding the lived reality.
This study gathers diverse primary sources written by Republican writers from various educational and political backgrounds and interprets them from a rare perspective, thus filling a research gap. It promotes a fuller view of supernatural narratives in twentieth-century Chinese literature. In terms of reflecting the social and personal reality of the Republican era, the supernatural narratives supplement the realist fiction of the time
Marvellous real in the Middle East: a comparative study of magical realism in contemporary womenâs fiction
Magical realism has been studied extensively in relation to Latin America and subsequently in other parts of the world, yet the Middle East has not received adequate attention in academic scholarship. This PhD study examines a selection of contemporary female-authored narratives from the Middle East to establish an understanding of the practice of magical realism in this region. The selected texts for this study are: Raja Alemâs Fatma and My Thousand and One Nights; Shahrnush Parsipurâs Women Without Men and Touba and the Meaning of Night; Elif Shafakâs The Bastard of Istanbul and Gina B. Nahaiâs Moonlight on the Avenue of Faith.
This study firstly explores the concept of magical realism as a mode of writing and determines its relationship to the Middle Eastern context. It then evaluates the texts under scrutiny by examining how the narrative of magical realism is constructed and what the sources are of the magical component in these texts, specifically in relation to Middle Eastern mythology. It also investigates the ideological aspect behind the employment of magical realism and whether it serves any political goal. The analysis of the selected texts is approached from three standpoints, that is, from literary, mythological and ideological perspectives. I argue that magical realism serves various purposes and that it is applied from perspectives that can be regarded as marginal to their communitiesâ dominant values, to subvert mainstream ideology. I also demonstrate that the Middle East is a crucial place to investigate magical realism because of the numerous complex cultural values that interact with each other in this region, and which enrich the practice of magical realism
Womenâs Experiences of Accessing Breastfeeding and Perinatal Health Support in the Context of Intimate Partner Violence: An Interpretive Description Study
Background: Women experiencing intimate partner violence are at a heightened risk of negative perinatal and breastfeeding outcomes. This study explored the experiences of accessing breastfeeding support for women who endorse a history of intimate partner violence. A study of five in-depth semi-structured interviews were completed at 12-weeks postpartum with breastfeeding mothers with a history of intimate partner violence. Findings: Women expressed difficulties in accessing a healthcare provider who had specialized skill in breastfeeding support. Trust in their healthcare provider, built through displays of compassion and competence, was important to mitigate obstacles experienced during care access for this population. Trauma-and-violence-informed care principles were beneficial to the development of the therapeutic relationship in perinatal care. Women placed value on breastfeeding support received from both healthcare providers and social supports, which impacted mothersâ perceived breastfeeding support and self-efficacy. Further, mothers described increased levels of breastfeeding self-efficacy after engaging in a trauma-and-violence-informed care program aimed at supporting breastfeeding. Conclusions: Trauma-informed care may aid in the development of trust in the therapeutic relationship, which in turn impacts access to breastfeeding support and breastfeeding self-efficacy. The inclusion of trauma-and-violence informed principles in perinatal care may be effective at mitigating barriers to access for women who endorse a history of intimate partner violence. health care on how to employ trauma-informed breastfeeding care to may lead to better support for this population
How Students use the Services available from Lindenwood Universities Library
Student Assessment Scholars took on the Library Services stakeholder proposal. Their goal was to find how students use the service available from Lindenwood Universities Library. Through evidence, it was found that students have a positive sentiment towards the Lindenwoodâs Library Services. That the Students want longer hours, better marketing, and find one of the best services being the building itself. Lindenwood Universities Library Services are similar to the other schools in the athletic conference. Lindenwood University houses a Maker Lab, Career Services, and technology rentals like the other universities, but Lindenwood students were not aware of them. Overall, students were happy with the library\u27s services and wanted their ability to use the services to be extended. The LARC is currently open 78 hours a week and the average of the other schoolâs library hours is 92. To compete with other schools in the athletic conference and increase students use and satisfaction of Library Services, they should first work towards extending their hours
Unraveling the effect of sex on human genetic architecture
Sex is arguably the most important differentiating characteristic in most mammalian
species, separating populations into different groups, with varying behaviors, morphologies,
and physiologies based on their complement of sex chromosomes, amongst other factors. In
humans, despite males and females sharing nearly identical genomes, there are differences
between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides
the genome with a distinct hormonal milieu, differential gene expression, and environmental
pressures arising from gender societal roles. This thus poses the possibility of observing
gene by sex (GxS) interactions between the sexes that may contribute to some of the
phenotypic differences observed. In recent years, there has been growing evidence of GxS,
with common genetic variation presenting different effects on males and females. These
studies have however been limited in regards to the number of traits studied and/or
statistical power. Understanding sex differences in genetic architecture is of great
importance as this could lead to improved understanding of potential differences in
underlying biological pathways and disease etiology between the sexes and in turn help
inform personalised treatments and precision medicine.
In this thesis we provide insights into both the scope and mechanism of GxS across the
genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK
Biobank. We found small yet widespread differences in genetic architecture across traits
through the calculation of sex-specific heritability, genetic correlations, and sex-stratified
genome-wide association studies (GWAS). We further investigated whether sex-agnostic
(non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we
studied the potential functional role of sex differences in genetic architecture through sex
biased expression quantitative trait loci (eQTL) and gene-level analyses.
Overall, this study marks a broad examination of the genetics of sex differences. Our findings
parallel previous reports, suggesting the presence of sexual genetic heterogeneity across
complex traits of generally modest magnitude. Furthermore, our results suggest the need to
consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms
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