1,689 Works

The Horizon 2020 Project SURE: Deliverable 7.2 - Report on Laterals Stability Modelling

John-Paul Latham, Ado Farsi, Jiansheng Xiang & Bin Chen
In this deliverable, the objectives of the Imperial College team are to consider jetted boreholes in the context of conventional borehole wall-rock stability analysis and to utilise an in-house advanced combined finite-discrete element code to examine the wall-rock failure process for jetted holes. The geomechanical modelling of Lateral Stability in D7.2 presented here is in addition to the main focus on modelling the water-jetting breakdown of the rock itself, reported in D7.1.

Structured Assessment of Competency in Polypectomy

Sachin Gupta
Currently, there is no national endoscopic database in England. Information regarding the volume of therapeutic endoscopic procedures such as polypectomy is obtained mainly from small prospective studies. We examined the Hospital Episode Statistics (HES) national database to assess the number of patients who underwent a therapeutic polypectomy for a primary diagnosis of a benign colorectal polyp over a 10 year period, as well as analysing outcomes from the first three years of bowel cancer screening...

Mathematical modelling of cardiovascular disease low dose ionising radiation data analyses

Anna Gola
Cardiovascular disease (CVD) is the major cause of morbidity and mortality in many developing and developed countries. This dissertation proposes a framework for gaining a greater understanding of the inflammatory process that is thought to result in the development of atherosclerosis and effects of radiation on the subsequent cardiovascular disease through statistical analysis and mathematical modelling of this process. The potential effect of low dose radiation in atherosclerotic initiation and progression is assessed utilising data...

Role of Gut Microbiome-Host Metabolic Interactions in Metabolic Diseases

Renaud Mestdagh
The metabolic phenotype of any complex organism is dependent on a complex series of host and gut microbial gene (microbiome) interactions with diet. The microbiome itself can be affected by environmental factors such as stress, exposure to xenobiotics, lifestyle, and alterations in the mammalian-microbial-metabolic axis are associated with changes in disease factors. To understand further the impact of the commensal microbiota on the host metabolism, germ-free (GF) animals, inoculated with individual bacterial strains or complex...

The influence of miRNAs on variation of gene expression during T-cell development

Rory Blevins
MicroRNAs (miRNAs) are small non-coding RNAs which regulate gene expression post-transcriptionally, by binding to specific mRNAs. It has been suggested that miRNAs have a role in "canalising" development and reducing variability in gene expression. Using conditional deletions of the miRNA biogenesis enzyme Dicer in mice, I investigated the effect of miRNA depletion on gene expression during T-cell development. I used flow cytometry to obtain the distribution of proteins on a single cell basis. Proteins encoded...

NMR-based metabonomics of pre-clinical models of isoniazid and gentamicin toxicity

Katharine Cunningham
An individual's response to drug therapy is the result of complex interactions between environmental and genetic factors. The ability to characterise inter-individual variation in response to pharmaceutical intervention is of particular importance in a clinical setting, where variation in response can result in therapeutic failure or adverse effects in individuals or sub-populations of patients. Given the success of NMR-based techniques for metabolic profiling, this thesis focused on characterisation of the systems-wide endogenous metabolic response to...

Brain development in fetal ventriculomegaly

Vanesa Kyriakopoulou
Introduction Fetal ventriculomegaly is the most common detectable central nervous system abnormality affecting 1% of fetuses and is associated with abnormal neurodevelopment in childhood. Neurodevelopmental outcome is partially predictable by the 2D size of the ventricles in the absence of other abnormalities while the aetiology of the dilatation remains unknown. The main aim of this study was to investigate brain development in the presence of isolated ventriculomegaly during fetal and neonatal life. Methods Fetal brain...

Temporal expression of neurochemical markers in primary sensory neurones in traumatic and non-traumatic models of neuropathic pain

Edward Boateng
Introduction: Expression of neurochemical markers in dorsal root ganglion (DRG) has been shown to underlie nerve injury induced neuropathic pain and are usually examined once post injury in rodent models. Here I hypothesize that neurochemical markers are expressed differentially at various time points post nerve injury and that expression of these markers differ between traumatic and non-traumatic models of neuropathic pain, thus reflecting variations in pathophysiology. In two different rat models of neuropathic pain, namely,...

Evaluation of robotic catheter technology in complex endovascular intervention

C.V. Theodoreli-Riga
The past four decades have witnessed tremendous strides in the evolution of endovascular devices and techniques. Catheter-based intervention has revolutionized the management of arterial disease allowing treatment of aortic and peripheral pathologies via a minimally invasive approach. Despite the exponential advances in endovascular equipment, devices and techniques, catheter-based endovascular intervention has certain morphological and technological constraints. Complex patient anatomy, technological impediments and suboptimal fluoroscopic imaging, can make endovascular intervention challenging using traditional endovascular means. Conventional...

Spatial Epidemiology and the Integrated Control of Malaria and Lymphatic Filariasis in Africa

Hannah Claire Slater
Malaria and lymphatic filariasis (LF) cause the largest public health burden of all vector-borne diseases worldwide. Some 350-500 million clinical episodes and 1 million deaths each year are caused by malaria, of which approximately 60% and 80% respectively occur in Africa. More than 50 million people are also thought to be infected with lymphatic filariasis in 39 endemic countries in sub-Saharan Africa, with approximately 14.6 million individuals living in these endemic countries estimated to suffer...

The Role of Acute Care Managers in Quality of Care and Patient Safety

Anam Parand
Healthcare managers have a responsibility for the standard of their services and patient care delivered. Their work is thought to be essential in achieving and improving high quality care and patient safety. However, little is empirically known about their role in this. This thesis investigates acute care managerial work and impact in the context of quality of care and patient safety. It draws upon power and work-activity group theories and literature from other industries to...

A study of the characteristics and dynamics of women at heightened risk of HIV in rural Zimbabwe

Jocelyn Elmes
Among many behaviour changes associated with recent declines in HIV prevalence in Zimbabwe, the number of men reporting buying sex halved between 1999 and 2005 possibly due to economic deterioration reducing disposable income. As the economy recovers, a key question is how this is reflected in sexual behaviour trends. A recent modelling analysis of the modes of transmission of HIV in Zimbabwe suggested diminished role for sex work in driving new infections. A central conclusion...

Design and synthesis of CXCR4-specific tracers for positron emission tomography

Guillaume Pierre Charles George
Molecular imaging is an ideal platform for non-invasive detection and assessment of cancer. In recent years, the targeted imaging of CXCR4, a chemokine receptor that has been associated with tumour metastasis, has become an area of intensive research. CXCR4 is a GPCR whose interaction with its natural ligand SDF-1α is essential for embryo development and haematopoiesis. Over-expression of this receptor is associated with aggressive types of cancer and potentially metastatic tumours. Several classes of CXCR4...

Blood DNA methylation biomarkers for breast cancer risk

Kevin Brennan
Breast cancer is the most common malignancy affecting women worldwide with an average lifetime risk of 12%. Risk is affected by age, family history, genetics, reproductive factors and environmental exposures, however many unknown risk factors may exist. Regular screening, lifestyle advice and preventative therapy may be offered to women at highest risk; however in the absence of high-penetrance mutations, personal breast cancer risk cannot be accurately estimated. Risk biomarkers are therefore required to help improve...

Development of Molecular Probes Responsive to Matrix Metalloproteinases

Sheena Cowell
Matrix metalloproteinases (MMPs) have been identified as biomarkers for cancer, offering prognostic potential. However, they lack non-invasive detection. This thesis highlights the work carried out on the design, synthesis and development of 19F MRI probes for the molecular imaging of MMP activity. The design of these MMP-activated imaging agents was based on the paramagnetic effects of gadolinium(III) on the NMR/MRI signal of a CF3 group in close proximity to the metal cation. 1st generation probes...

Synthesising Nucleoside Analogues For Imaging Proliferation In Cancer And Other Biomedical Applications

Andreas Doepner
Rapidly proliferating cells, such as cancerous cells, show increased reliance on deoxyribonucleic acid (DNA) salvage pathways for producing nucleotides required for DNA synthesis. As such targeting these salvage pathways using radiolabelled nucleosides can provide a means of imaging the extent of proliferation within a tissue using positron emission tomography (PET). This permits the detection of malignant growths. Thiothymidine and 2’-deoxy-2’,2’-difluoro nucleoside analogues are currently being evaluated for theoretically superior properties in comparison to 3’-deoxy-3’-[18F]-fluorothymidine (FLT),...

Drinking water salinity and the risk of (pre)eclampsia and gestational hypertension in coastal Bangladesh: impacts of climate change

Aneire Khan
Hypertensive disorders in pregnancy are among the leading causes of death and disabilities in women of child-bearing age in low-income countries. Despite the high burden, the pathophysiology and aetiology of these disorders are poorly understood, making effective prevention difficult. Excessive dietary salt intake is an established risk factor for hypertension, but much less is known about the health effects of water salinity. This epidemiological study investigated the relationship between high salinity in drinking water and...

Cohesin dynamics during meiotic prophase

Sarah Testori
For faithful segregation during meiosis, chromosomes must be physically linked by both sister chromatid cohesion (SCC), provided by cohesin, and at least one crossover (CO). In mitosis, cohesin is dynamically associated with chromatin and this has been shown to be crucial for the repair of DSBs. Although DSBs are purposely made to start meiotic recombination, it is unknown if meiotic cohesin is dynamically associated with chromatin. However, cohesin loss or degradation is thought to be...

The clinical burden of respiratory syncytial virus (RSV) bronchiolitis among infants in the United Kingdom (UK)

Joanna Catherine Murray
Background and Aim: Studies of the epidemiology of respiratory syncytial virus (RSV) bronchiolitis to date have been small; focused only on the hospital setting and selective groups of high-risk infants such as those born preterm; lacked long-term follow-up and few have been based on data from the United Kingdom (UK). Hence, the existing evidence base was likely to underestimate the scale and impact of RSV on health in UK infants. The aim of this thesis...

Investigating the role and regulation of the AMPK-related kinase NUAK1

Duncan Bull
AMP-activated protein kinase (AMPK) is a well characterised central regulator of energy homeostasis with many downstream substrates and potential therapeutic targets. Recently several kinases related to AMPK have been identified which are activated by the same upstream kinase, LKB1, and share significant sequence homology with the catalytic α subunit of AMPK. Previous studies have implicated NUAK1, one of these related kinases, in cell cycle regulation and other studies have identified various partner proteins but as...

Functional characterisation of the genomes of rat models of human diseases

Santosh Atanur
Large numbers of inbred laboratory rat strains have been developed in the past 100 years by phenotype-driven selective breeding for the study of a range of disease phenotypes. The spontaneously hypertensive rat (SHR) is the most widely studied animal model of hypertension. The SHR Genome was sequenced with 10.7X coverage, and ~4 million genomic variants between SHR and the BN reference genome were identified. Analysis of the SHR genome revealed that cis expression quantitative trait...

Development of a new, minimally invasive, full thickness excision technique for early colonic neoplasia

Adela Brigic
Introduction of bowel cancer screening programmes internationally has resulted in a significant shift in diagnosis towards early stage disease. In addition, the number of patients diagnosed with complex benign colorectal polyps is increasing. Advanced endoscopic techniques including endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) as well as transanal endoscopic microsurgery (TEMS) are being increasingly utilised for excision of early rectal neoplasia. An equivalent surgical technique is currently not available for colonic lesions, and...

Investigating the role of heme oxygenase and oxidative stress in oesophagogastric cancer

Oliver Priest
Background: Molecular mechanisms underlying gastric and oesophageal cancer include alterations in growth factors, cytokines and cell adhesion molecules. Heme oxygenase (HO) enzyme catalyses the degradation of heme and generates bilirubin and carbon monoxide that have antioxidant, anti-inflammatory and anti-apoptotic activities. HO enzyme is implicated in the biology of cancer by its effects on cell growth and resistance to apoptosis. The roles of HO-1 and HO-2 enzymes in cancer cell growth are poorly understood, with reports...

CXCR4 as a target for preclinical Positron Emission Tomography of cancer

Elizabeth Stevens
The chemoattractive interactions of the chemokine stromal derived factor-1 (SDF1) and its receptor CXCR4 play a key role in tumour metastasis, with CXCR4 expression found to be significantly higher in cancers with aggressive phenotypes. There is therefore an impetus for non-invasive means to sensitively identify tumours prone to progression. As such, the aim of this work was to develop a number of novel CXCR4 antagonists to assess their suitability as imaging radiotracers for positron emission...

Patient and public involvement in the benefit-risk assessment of medicines and regulatory decision-making

Kimberley Hockley
Currently, regulators make marketing authorisation decisions based on the benefit-risk balance of a treatment with little input from patients and the public. The aims of this thesis are to apply systematic methods of benefit-risk assessment proposed for use in regulatory decision-making, and examine how they can incorporate patient and public involvement. These aims were met through the investigation of three case studies: efalizumab, rimonabant, and natalizumab. Efalizumab (indication: plaque psoriasis) was withdrawn from the market...

Registration Year

  • 2020
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Resource Types

  • Text
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Affiliations

  • Imperial College London
    1,689
  • University of Strathclyde
    2
  • University of North Carolina at Chapel Hill
    1
  • University of Warwick
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  • University of Edinburgh
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  • University of East Anglia
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  • University of Manchester
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  • University College London
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  • Chatham House
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  • University of Sydney
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