14,742 research outputs found
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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 place where curses are manufactured : four poets of the Vietnam War
The Vietnam War was unique among American wars. To pinpoint its uniqueness, it was necessary to look for a non-American voice that would enable me to articulate its distinctiveness and explore the American character as observed by an Asian. Takeshi Kaiko proved to be most helpful. From his novel, Into a Black Sun, I was able to establish a working pair of 'bookends' from which to approach the poetry of Walter McDonald, Bruce Weigl, Basil T. Paquet and Steve Mason. Chapter One is devoted to those seemingly mismatched 'bookends,' Walt Whitman and General William C. Westmoreland, and their respective anthropocentric and technocentric visions of progress and the peculiarly American concept of the "open road" as they manifest themselves in Vietnam. In Chapter, Two, I analyze the war poems of Walter McDonald. As a pilot, writing primarily about flying, his poetry manifests General Westmoreland's technocentric vision of the 'road' as determined by and manifest through technology. Chapter Three focuses on the poems of Bruce Weigl. The poems analyzed portray the literal and metaphorical descent from the technocentric, 'numbed' distance of aerial warfare to the world of ground warfare, and the initiation of a 'fucking new guy,' who discovers the contours of the self's interior through a set of experiences that lead from from aerial insertion into the jungle to the degradation of burning human
feces. Chapter Four, devoted to the thirteen poems of Basil T. Paquet, focuses on the continuation of the descent begun in Chapter Two. In his capacity as a medic, Paquet's entire body of poems details his quotidian tasks which entail tending the maimed, the mortally wounded and the dead. The final chapter deals with Steve Mason's JohnnY's Song, and his depiction of the plight of Vietnam veterans back in "The World" who are still trapped inside the interior landscape of their individual "ghettoes" of the soul created by their war-time experiences
Creativity and security as a cultural recipe for entrepreneurship
We posit that societal cultural values of creativity and security are associated with the likelihood that a person will engage in a business start-up. Creativity supports the opportunity identification and security the opportunity exploitation aspects of entrepreneurship. In contrast, both emphasis on performance and acceptance of risk-taking may not play the role that is typically assumed. To verify our hypotheses we construct a multilevel dataset, combining Global Entrepreneurship Monitor individual-level data with country-level data from the World Values Survey. We use a multilevel logit model to address the hierarchical structure of our data. We found that odds of start-up engagement are higher if people in a society value security, yet also appreciate thinking up new ideas and being creative. Our results support McCloskey’s distinction between aristocratic and bourgeois values, and John and Storr’s proposition that different cultural traits support different aspects of entrepreneurship
Iam hiQ—a novel pair of accuracy indices for imputed genotypes
Background
Imputation of untyped markers is a standard tool in genome-wide association studies to close the gap between directly genotyped and other known DNA variants. However, high accuracy with which genotypes are imputed is fundamental. Several accuracy measures have been proposed and some are implemented in imputation software, unfortunately diversely across platforms. In the present paper, we introduce Iam hiQ, an independent pair of accuracy measures that can be applied to dosage files, the output of all imputation software. Iam (imputation accuracy measure) quantifies the average amount of individual-specific versus population-specific genotype information in a linear manner. hiQ (heterogeneity in quantities of dosages) addresses the inter-individual heterogeneity between dosages of a marker across the sample at hand.
Results
Applying both measures to a large case–control sample of the International Lung Cancer Consortium (ILCCO), comprising 27,065 individuals, we found meaningful thresholds for Iam and hiQ suitable to classify markers of poor accuracy. We demonstrate how Manhattan-like plots and moving averages of Iam and hiQ can be useful to identify regions enriched with less accurate imputed markers, whereas these regions would by missed when applying the accuracy measure info (implemented in IMPUTE2).
Conclusion
We recommend using Iam hiQ additional to other accuracy scores for variant filtering before stepping into the analysis of imputed GWAS data
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Co-design As Healing: Exploring The Experiences Of Participants Facing Mental Health Problems
This thesis is an exploration of the healing role of co-design in mental health. Although co-design projects conducted within mental health settings are rising, existing literature tends to focus on the object of design and its outcomes while the experiences of participants per se remain largely unexplored. The guiding research question of this study is not how we design things that improve mental health, but how co-designing, as an act, might do so.
The thesis presents two projects that were organized in collaboration with the mental health charity Islington Mind and the Psychosis Therapy Project (PTP) in London.
The project at Islington Mind used a structured design process inviting participants to design for wellbeing. A case study analysis provides insights on how participants were impacted, summarizing key challenges and opportunities.
The design at PTP worked towards creating a collective brief in an emergent fashion, finally culminating in a board game. The experiences of participants were explored through Interpretative Phenomenological Analysis (IPA), using semi-structured interview data. The analysis served to identify key themes characterising the experience of co-design such as contributing, connecting, thinking and intentioning. In addition, a mixed-methods analysis of questionnaires and interview data exploring participants' wellbeing, showed that all participants who engaged fairly consistently in the project improved after the project ended, although some participants' scores returned to baseline six months later.
Reflecting on both projects, an approach to facilitation within mental health is outlined, detailing how the dimensions of weaving and layered participation, nurturing mattering and facilitating attitudes interlace. This contribution raises awareness of tacit dimensions in the practice of facilitation, articulating the nuances of how to encourage and sustain meaningful and ethical engagement and offering insights into a range of tools. It highlights the importance of remaining reflexive in relation to attitudes and emotions and discusses practical methodological and ethical challenges and ways to resolve them which can be of benefit to researchers embarking on a similar journey.
The thesis also offers detailed insights on how methodologies from different fields were integrated into a whole, arguing for transparency and reflexivity about epistemological assumptions, and how underlying paradigms shift in an interdisciplinary context.
Based on the overall findings, the thesis makes a case for considering design as healing (or a designerly way of healing), highlighting implications at a systems, social and individual level. It makes an original contribution to our understanding of design, highlighting its healing character, and proposes a new way to support mental health. The participants in this study not only had increased their own wellbeing through co-designing, but were also empowered and contributed towards healing the world. Hence, the thesis argues for a unique, holistic perspective of design and mental health, recognizing the interconnectedness of the individual, social and systemic dimensions of the healing processes that are ignited
Exploring the Structure of Scattering Amplitudes in Quantum Field Theory: Scattering Equations, On-Shell Diagrams and Ambitwistor String Models in Gauge Theory and Gravity
In this thesis I analyse the structure of scattering amplitudes in super-symmetric gauge and gravitational theories in four dimensional spacetime, starting with a detailed review of background material accessible to a non-expert. I then analyse the 4D scattering equations, developing the theory of how they can be used to express scattering amplitudes at tree level. I go on to explain how the equations can be solved numerically using a Monte Carlo algorithm, and introduce my Mathematica package treeamps4dJAF which performs these calculations. Next I analyse the relation between the 4D scattering equations and on-shell diagrams in N = 4 super Yang-Mills, which provides a new perspective on the tree level amplitudes of the theory. I apply a similar analysis to N = 8 supergravity, developing the theory of on-shell diagrams to derive new Grassmannian integral formulae for the amplitudes of the theory. In both theories I derive a new worldsheet expression for the 4 point one loop amplitude supported on 4D scattering equations. Finally I use 4D ambitwistor string theory to analyse scattering amplitudes in N = 4 conformal supergravity, deriving new worldsheet formulae for both plane wave and non-plane wave amplitudes supported on 4D scattering equations. I introduce a new prescription to calculate the derivatives of on-shell variables with respect to momenta, and I use this to show that certain non-plane wave amplitudes can be calculated as momentum derivatives of amplitudes with plane wave states
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
How to Be a God
When it comes to questions concerning the nature of Reality, Philosophers and Theologians have the answers.
Philosophers have the answers that can’t be proven right. Theologians have the answers that can’t be proven wrong.
Today’s designers of Massively-Multiplayer Online Role-Playing Games create realities for a living. They can’t spend centuries mulling over the issues: they have to face them head-on. Their practical experiences can indicate which theoretical proposals actually work in practice.
That’s today’s designers. Tomorrow’s will have a whole new set of questions to answer.
The designers of virtual worlds are the literal gods of those realities. Suppose Artificial Intelligence comes through and allows us to create non-player characters as smart as us. What are our responsibilities as gods? How should we, as gods, conduct ourselves?
How should we be gods
A Cornish palimpsest : Peter Lanyon and the construction of a new landscape, 1938-1964
The thesis examines the emergence of Peter Lanyon as one of the few truly innovative British landscape painters this century. In the Introduction I discuss the problematic nature of landscape art and consider the significance of Lanyon's discovery that direct description and linear perspective can be replaced with allusive representational elements by fusing the emotional and imaginative life of the artist with the physical activity of painting. Chapter One concentrates on the period 1936-8 when Lanyon was taught by Borlase Smart, a key figure in the St Ives art colony between the wars. Chapter Two examines the influence of Adrian Stokes and the links between Lanyon's painting and the theories developed in books such as Colour and Form and The Quattro Cento. Chapter Three analyses the period 1940-45 when Lanyon was directly influenced by the constructivism of Nicholson, Hepworth and Gabo. I look closely at their approaches to abstraction and assess Lanyon's relative position to them. The importance of Neo-Romanticism and the status of St Ives as a perceived avant-garde community is also addressed. In Chapter Four I discuss how Lanyon resolved to achieve a new orientation in his art on his return from wartime service with the RAF by synthesising constructivism, and traditional landscape. The Generation and Surfacing Series demonstrate his preoccupation with a sense of place, a fascination with the relationships between the human body and landscape and his struggle to find a technique and style that was entirely his own. His sense of existential insideness is discussed in Chapter Five through an examination of the work derived from Portreath, St. Just and Porthleven - key places in Lanyon's psychological attachment to the landscape of West Penwith. In Chapter Six I examine Lanyon's attachment to myths and archetypal forms, tracing the influence of Bergson's vitalist philosophy as well as his use of Celtic and classical motifs. Chapter Seven is a discussion of the malaise evident in Lanyon's work by 1955 and the impact of American Abstract Expressionism at the Tate Gallery a year later. In the summer of 1959 Lanyon joined the Cornish Gliding Club and Chapter Eight looks at how this necessitated a dynamic, expanded conception of the landscape and a re-thinking of relations within the picture field. The ability to dissolve boundaries encouraged him to break down distinctions between painting and construction so that abstract sculptural elements were now assembled into independent works of art. Finally, Chapter Nine assesses Lanyon's overall position in relation to his early influences and to St Ives art as a whole, his response to new directions in art coming out of London and NewYork in the early 1960s and the importance of travel as a stimulus for further realignment in his artistic and topographical horizons. His pictorial inventiveness and vitality remained unabated at the time of his death and would undoubtedly have continued to be enriched by travel abroad and contact with new movements in modem art on both sides of the Atlanti
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Privacy-aware Smart Home Interface Framework
Smart home user interfaces are pervasive and shared by multiple users who occupy the space. Therefore, they pose a risk to interpersonal privacy of occupants because an individual’s sensitive information can be leaked to other co-occupants (information privacy), or they can be disturbed by intrusions into their personal space (physical privacy) when the co-occupant interacts with the smart home user interfaces. This thesis hypothesises that interpersonal privacy violations can be mitigated by adapting the user interface layer and presents insights into how to achieve usable user interface adaptation to mitigate or minimise interpersonal privacy violations in smart homes.
The thesis reports two case studies and two user studies. The first case study identifies the key characteristics needed to model the rich context of interpersonal privacy violations scenarios. Then it presents knowledge representation models that are required to represent the identified characteristics and evaluates them for adequacy in modelling the context information of interpersonal privacy violation scenarios. The second case study presents a software architecture and a set of algorithms that can detect interpersonal privacy violations and generate usable user interface adaptations. Then it evaluates the architecture and the algorithms for adequacy in generating usable privacy-aware user interface adaptations. The first user study (N=15) evaluates the usability of the adaptive user interfaces generated from the framework where storyboards were used as the stimulant. Extending the findings from the usability study and expanding the coverage of example scenarios, the second user study (N=23) evaluates the overall user experience of the adaptive user interfaces, using video prototypes as the stimulant.
The research demonstrates that the characteristics identified, and the respective knowledge representation models adequately captured the context of interpersonal privacy violation scenarios. Furthermore, the software architecture and the algorithms could detect possible interpersonal privacy violations and generate usable user interface adaptations to mitigate them. The two user studies demonstrate that the adaptive user interfaces, when used in appropriate situations, were a suitable solution for addressing interpersonal privacy violations while providing high usability and a positive user experience. The thesis concludes by providing recommendations for developing privacy-aware user interface adaptations and suggesting future work that can extend this research
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