1,689 Works

Using mathematical models to characterize HIV epidemics for the design of HIV prevention strategies

Sharmistha Mishra
Since 2000, we have been trying to characterize and classify HIV epidemics to guide the strategic design of HIV prevention policies and focus HIV programmes and resource allocation by a regions’ epidemic type. We have used arbitrary thresholds of HIV prevalence across different risk-groups in a given population, ‘static’ mathematical models and classical epidemiological measures of the population attributable fraction that do not account for chains of transmission. As a result, these traditional approaches could...

The application of innovative virtual world technologies to enhance healthcare education

Vishal Arun Patel
The World Wide Web has evolved leading to the development of three- dimensional virtual worlds. These are online, accessible environments through which a user may engage, communicate and interact via their digital self, known as their avatar. These virtual worlds offer the opportunity for further content to be generated in order to provide new environments and simulations. This research work explores the potential of virtual worlds in providing an educational platform for healthcare professionals. In...

Dynamics of influenza A in non-human hosts

Amy Pinsent
The emergence of novel influenza A viral lineages to which there is limited or no immunity remains an on-going concern for human and animal public health. At least three of the pandemics reported in human hosts during the 20th and 21st century are believed to have emerged as a result of reassortment between human, avian and swine viruses circulating at the time. The emergence of novel lineages with pandemic potential is frequently believed to occur...

Social network sites as a means to collect health behaviour data for young people; a comparative-descriptive cross sectional study

Fahdah Alshaikh
This thesis is original in the sense that it examines a relatively new method of collecting data using Social Network Sites, and explores the feasibility of this method for survey research providing valuable data regarding health behaviours among young Saudis. Aims: The primary aim of this study is to assess the feasibility of Social Network Sites (SNS) as a mode of collecting data for health behavioural surveys by comparing data collected from an SNS-based questionnaire...

The effects of the quality of primary care on diabetes outcomes

Daniel Chester Gibbons
Background Diabetes mellitus is a chronic condition primarily characterised by elevated levels of plasma glucose due to a lack of insulin. Diabetes is a risk factor for a number of acute and chronic complications and is associated with significant morbidity and mortality, the risks and impact of which may be modifiable through high-quality primary care. This thesis examines the relationship between the quality of primary care and emergency admissions, readmissions and mortality. Methodology Associations between...

Statistical analysis of ‘–omics’ data: developments and applications

Gianluca Campanella
In recent years, increasingly efficient molecular biology techniques created new opportunities to harness large-scale repositories of biological material collected in epidemiological studies; however, methods to manipulate and analyse the wealth of information thus generated have lagged behind. The introductory chapter of this thesis presents the multifaceted field of ‘computational epidemiology’ from the perspectives of molecular biology, measurement theory, and statistical modelling. Focusing on measurement of DNA methylation levels, the author also reviews the state of...

Anthropometric and genetic determinants of cardiac morphology and function

Antonio De Marvao
Background Cardiac structure and function result from complex interactions between genetic and environmental factors. Population-based studies have relied on 2-dimensional cardiovascular magnetic resonance as the gold-standard for phenotyping. However, this technique provides limited global metrics and is insensitive to regional or asymmetric changes in left ventricular (LV) morphology. High-resolution 3-dimensional cardiac magnetic resonance (3D-CMR) with computational quantitative phenotyping, might improve on traditional CMR by enabling the creation of detailed 3D statistical models of the variation...

Total work and health in later life: a life course study

Omobolaji Akinwale
Background and aim: Work is a fundamental activity in all societies. While employment is an essential means of economic growth and improved living standards, it is now widely accepted that appropriate employment also helps to create good health and is among the most important social determinants of health that contribute to health inequalities. Less is known, however about the health effects of other work activity alongside paid employment. The interplay between different forms of work...

Modelling Crebbp loss in BCL2 driven non-Hodgkin’s lymphoma

Joanna Camilla Dawes
Non-Hodgkin’s lymphomas (NHL) are a spectrum of hematopoietic cancer accounting for 4% of new cancer diagnoses each year. Approximately 95% of all NHL are of B-cell origin; diffuse large B-cell lymphomas (DLBCL) and follicular lymphoma (FL) accounting for 30-40% and 20% of B-NHL respectively. Recent human mutation profiling and resequencing studies have shown that CREBBP and BCL2 are frequently mutated, early events in B-NHL that are often are concurrent. This thesis presents a study of...

The influence of temperature and age-dependent survival on Anopheles gambiae s.s. life-history and population dynamics

Céline Christiansen-Jucht
Malaria transmission depends on the life-history parameters, and population dynamics, of its vectors, and particularly on the survival of adult Anopheles mosquitoes, the main vector of malaria in Africa. These dynamics are sensitive to climatic and environmental factors, and temperature is a particularly important driver, though the exact extent of this sensitivity is not well established. Some data currently exist on the influence of constant and fluctuating environmental temperature on Anopheles gambiae s.s. survival but...

Elucidating Schwann cell reprogramming

Elizabeth Byrne
The peripheral nervous system, unlike the central nervous system, has an exceptional capacity for regeneration following injury. This is due to the remarkable plasticity of the Schwann cells (SC), which are able to reprogramme, following injury, to a progenitor like cell which facilitates peripheral nerve repair. Current knowledge on the molecular basis of this reprogramming is incomplete and we are lacking a global overview of the transcriptional events that occur in SC following nerve injury...

The role and regulation of FOXM1 in breast cancer DNA repair and epirubicin resistance

Lara Jorge Monteiro
Breast cancer is the most common malignancy in women, with 1 in 9 of all British and American women developing this disease in their lifetimes. FOXM1 is implicated in genotoxic drug resistance but its role and mechanism of action remain unclear. This work demonstrates that the inhibition of FOXM1 renders MCF-7 epirubicin resistant cells (MCF-7 EpiR) more susceptible to DNA double-strand breaks (DSBs) induced by epirubicin. Conversely, the ectopic expression of FOXM1 can increase cell...

Application of Bayesian hierarchical models for the analysis of complex clinical trials: an analysis strategy based on two case studies in dental research

Juan Guillermo Gonzalez-Maffe
Aim: To develop a strategy for the analysis of complex experiments using Bayesian hierarchical models, and demonstrate the advantage of the Bayesian formulation when analysing complex experiments. Methods: There is increased popularity in designing complex experiments; such experiments help amplify the efficiency of clinical research. The Bayesian approach is a natural candidate to tackle complex problems in a straightforward manner as it handles efficiently large amounts of missing data and multivariate responses data. Joint models...

Harmonised ambient air pollution and road traffic noise exposures linked to cardiovascular outcomes in European cohorts

Yutong Cai
Ambient air pollution and traffic-related noise are the two leading environmental risk factors for health in Europe. Associations between long-term exposure to air pollution or noise and cardiovascular diseases (CVD) were not entirely consistent across previous studies in adults. Moreover, noise may confound the relationship between air pollution and CVD, and vice versa. This PhD project was conducted to study the separate and joint effects of both air pollution and noise on 1) CVD blood...

Interactions of microRNA27a and prohibitin in the androgen signalling pathway

Claire E. Fletcher
Prohibitin (PHB) is a highly conserved, multi-functional protein that acts as a tumour suppressor and androgen receptor (AR) corepressor. We found that downregulation of PHB by androgens is required to drive androgen-dependent prostate cancer cell growth. This effect can be mimicked through the use of PHB siRNA, whereby reduction in PHB protein levels enhances cancer cell and xenograft tumour growth. Conversely, PHB overexpression results in rapid accumulation of prostate cancer cells in G0/G1. The potential...

The role of the co-chaperone p23 in Androgen signalling and prostate cancer

Laia Querol I Cano
The binding of ligand by cytoplasmic Androgen Receptor (AR) is a critical step in androgen signalling. In the cytoplasm, unliganded AR requires the recruitment and activity of several factors and chaperones that stabilise the receptor preventing its degradation and maintaining it in a ligand-binding competent state. Heat shock protein 90 (HSP90) and p23 are essential components of this apo-receptor complex for the AR as well as several other steriod receptors. p23 is a highly conserved...

The potential of fetal cell therapy for osteogenesis imperfecta using placenta derived stem cells

Gemma NIcole Jones
Human mesenchymal stromal/stem cells (MSC) isolated from aborted first trimester fetal bone marrow (BM) hold promise for use in tissue engineering applications and cell-based therapies due to their advantageous characteristics compared to their adult BM-MSC counterparts; faster growth kinetics, active telomerase, smaller size and higher differentiation potency. However, their isolation is restricted ethically and technically and therefore there is a need to identify a cell source with high therapeutic potential that is easily accessible in...

Influence of the intestinal microbiota on the immune response to oral poliovirus and rotavirus vaccines in a low-income community in south India

Edward Parker
Oral vaccines have consistently underperformed in the low-income countries where they are needed most. This has formed a potent obstacle to several public health initiatives that rely on such vaccines, including the polio eradication endgame. This thesis examines the hypothesis that the composition of the intestinal microbiota – including both pathogenic and commensal microbes – contributes to the impaired performance of oral vaccines in low-income countries. Based on a systematic review and meta-analysis, we observed...

Access to primary health care in England: policy, theory, and evidence

Thomas Edward Cowling
Background: The U.K. Government plans to improve access to general practice services in England, partly by extending the opening hours of these services. The Government expects this to enhance patient experience and reduce use of emergency hospital services. The thesis aims to provide empirical evidence relevant to these policy expectations. Methods: Three observational studies of a cross-sectional questionnaire-based survey—the GP Patient Survey—from 2011-12 to 2013-14 (2,912,535 respondents aged ≥18 years old and registered to 8,289...

Statistical implications of centralised care for estimating neonatal unit mortality rates

Shalini Santhakumaran
Monitoring clinical outcomes across healthcare providers is increasingly important in the UK National Health Service. Neonatal care is no exception, but care is centralised, so is delivered via co-ordinated networks of neonatal units (NNUs), with sicker infants treated in larger centres. This results in frequent transfers, but it is unclear how to attribute outcomes of transferred infants. Hierarchical regression is recommended for assessing performance of healthcare providers, but existing studies have either excluded transferred patients...

Collagen & aortopathy gene abnormalities in ehlers danlos syndrome (EDS) & sporadic thoracic aortic aneurysm & dissection (TAAD)

Ruwan Weerakkody
Introduction: Ehlers Danlos Syndrome(EDS) and Thoracic Aortic Aneurysm & Dissection(TAAD) comprise rare Mendelian vascular phenotypes associated with significant premature morbidity and mortality. New sequencing technologies may allow the better characterisation of their genetic basis, thereby informing clinical management and identifying novel molecular pathways. Methods: A combined strategy of targeted high-throughput sequencing to identify the mutational spectrum in known collagen and aortopathy-susceptibility genes and whole-exome sequencing to identify novel candidate genes was used in large cohorts...

Exploring interstitial mediators in burn injury

Dominic Friston
Burn injury remains a major clinical challenge to both survival and to quality of life. Its progressive, aberrant inflammation underlies the lethal dysfunction of various organs and the pain it induces is excruciating and notoriously difficult to manage. While it is known that burn injury’s complex local and disseminating pathology is orchestrated from the burned tissue, few studies have sought to characterise the local signalling environment. An enhanced understanding of the local and acutely temporally-dynamic...

Metabolic Profiling of Chronic Venous Disease

Sarah Onida
Introduction Chronic venous disease is a common condition with a diverse range of clinical presentations, including spider veins, varicose veins and venous ulceration. Despite its high prevalence, and varicose vein surgery being one of the most commonly performed procedures on the U.K. National Health Service, much is still unknown about this disease. The prevalence of disease, although described by a number of epidemiological studies, is poorly characterized, particularly due to diverse methodology employed in the...

Assessing the impact of mass deworming: changes in soil-transmitted helminth burden and characteristics, co-infections and the gut microbiome

Alice Van Antwerp Easton
Approximately two billion people worldwide are infected with a soil-transmitted helminth (STH) and could benefit from anthelmintic treatment. Evaluating the impact of mass drug administration (MDA) for STH infection, however, is highly challenging, due in part to the absence of a gold-standard diagnostic. This thesis examines the impact of MDA using both standard parasitological and novel molecular methods. Kato Katz (KK) provides false negative results in approximately 68% of Necator americanus infections detectable by quantitative...

Aldehyde metabolic reprogramming in oesophageal adenocarcinoma

Stefan Antonowicz
Oesophageal adenocarcinoma (OAC) has unmet clinical needs as the UK five-year survival is 14%. Efforts to enhance early diagnosis uncovered enriched volatile aldehydes in OAC patients’ breath, although their origins and fate are unknown. Following comprehensive bioinformatics analyses, it was hypothesised that detoxification loss enriches aldehydes in the transforming lower oesophagus. Pursuing this biology could help refine OAC breath testing, deepen understanding of oncogenesis and uncover therapeutic susceptibilities. This PhD aimed to describe OAC aldehyde...

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  • 2020
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