PhD theses


Current/recent theses

The relationship between non-alcoholic fatty liver disease (NAFLD) and diabetes  
Retinal functional hyperaemia in humans with and without type 1 diabetes  
The art of oncology: communicating survival expectancy to patients with cancer 
Costs and effectiveness of anticancer treatments
Quality of life and arm symptoms following axillary surgery for breast cancer
Exploring barriers to radiotherapy utilisation
Studies of cardiovascular disease and its treatment
Costs of premature mortality in Australia
Statistical methods addressing biases and inefficiencies in the design and analysis of clinical trials
Additive variance regression methods with application to measurement error models in clinical biomarker studies 
Efficacy of pre-hospital management of severe head injury by physician teams rather than paramedics 
The contribution of obesity, inflammation and autonomic function to the vascular health of adolescents with diabetes
Identifying molecular signatures that define insulin-producing cells
RNA-based Analysis for the Prediction of Islet Death: The RAPID Study
Non-invasive detection of subclinical atherosclerosis in high risk groups
The significance of internal mammary node metastasis in breast cancer
Advanced glycation end products and oxidative stress in diabetes and novel diabetes therapeutics

 

Current/recent theses details

Thesis title: The relationship between non-alcoholic fatty liver disease (NAFLD) and diabetes

PhD candidate: Kathryn Williams

Supervisor: Professor Stephen Twigg

Associate supervisors: Prof Anthony Keech, Dr Nick Shackel and A/Prof Mark Gorrell

Summary: Kathryn's reasearch aims to determine the frequency and implications of abnormal liver enzymes and non-invasive measures of liver fibrosis in populations with diabetes. In particular I would like to determine whether these abnormal measures in NAFLD may lead to increased rates and severity of diabetes complications. She also aims to examine novel blood markers that may indicate NAFLD severity.

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Thesis title: Retinal functional hyperaemia in humans with and without type 1 diabetes

PhD candidate: Jonathan E. Noonan

Supervisor: A/Prof Ecosse L. Lamoureux

Associate supervisors: A/Prof Alicia Jenkins, Prof Jie Jin Wang, Prof Gregory J. Dusting, A/Prof Glenn M. Ward

Summary:  Jon's research aims to explore the mechanisms of retinal vasodilation during flicker light stimulation and the potential causes of dysfunction in type 1 diabetes.

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Thesis title: The art of oncology: communicating survival expectancy to patients with cancer

PhD candidate: Belinda Kiely

Supervisor: Martin Stockler

Summary: Belinda's goal is improving communication of life expectancy to patients in a way that is realistic but maintains hope. Median survival is the measure that most cancer professionals are familiar with, but for patients the median is unnecessarily discouraging and frequently misinterpreted. Many interpret the median as a limit and do not realise that 50% of individuals live longer. Belinda and her colleagues have suggested framing information in terms of the chance of surviving rather than the chance of dying, as a way of conveying hope. They also suggest using multiples and fractions of the median to present typical, best-case and worst-case scenarios to patients rather than just a single estimate of the median.

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Thesis title: The costs and effectiveness of anticancer treatments

PhD candidate: Deme Karikios

Supervisor: Martin Stockler

Summary: The aims of these projects are to assess the cost-effectiveness of new anticancer drugs and identify their determinants. Specific objectives include: to systematically review recent evidence about the costs and cost-effectiveness of anticancer drugs; and to survey medical oncologists to determine their views on how treatment costs affect decision making, and how problems associated with the increasing costs of treatment may be resolved. Another key objective is to perform cost-effectiveness analyses of expensive anticancer treatments, on the basis of individual patient data from randomised trials conducted by the CTC. This includes the MAX trial of bevacizumab plus capecitabine in advanced colorectal cancer, and the ANZ0001 trial of capecitabine versus CMF in advanced breast cancer.

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Thesis title: Quality of life and arm symptoms following axillary surgery for breast cancer

PhD candidate: Michaella Smith

Supervisor: Martin Stockler

Summary: The aims of this project are to determine how best to measure, express, analyse and compare the effects of different operations on how women feel and progress after surgery for early breast cancer. This will be achieved by analysing longitudinal data on arm symptoms, functions, disabilities, body image and other aspects of quality of life, collected on 1088 women who participated in the RACS SNAC trial. The data also include arm measurements completed by doctors or nurses. Exploration, analysis and synthesis of these measures will provide important information about the effects of axillary clearance and sentinel node biopsy in early breast cancer. It will also generate new knowledge on how to design future studies comparing operations; especially how best to measure, express and compare their effects on patient-rated outcomes.

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Thesis title: Exploring barriers to radiotherapy utilisation

PhD candidate: Puma Sunderasan

Supervisor: Martin Stockler

Summary: The objectives of Puma's thesis projects are to: determine current radiotherapy utilisation rates in NSW; explore barriers to radiotherapy utilisation from the perspective of consumers (patients and carers) and their referring physicians; define the components of radiotherapy-related 'service inconvenienced'; and begin the development of a valid and reliable health-related quality of life tool that can accurately quantify radiotherapy-related inconvenience.

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Thesis title: Studies of cardiovascular disease and its treatment

PhD candidate: Jordan Fulcher

Supervisor: Anthony Keech

Summary: The NHMRC Clinical Trials Centre has gathered individual patient data on more than 169 000 patients participating in randomised trials of statin treatment. Jordan is currently undertaking systematic reviews of the large data sets to explore the effects of lipid-lowering treatment by sex, age and long-term follow-up, with a view to further investigating biological mechanisms for statin efficacy and safety in various populations.

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Thesis title: Costs of premature mortality in Australia

PhD candidate: Hannah Carter

Supervisor: Deborah Schofield

Summary: Decisions to publicly fund effective health interventions in Australia are generally based on costs that occur in the health sector alone. But premature mortality also reduces household income, savings and superannuation, tax revenue and economic productivity. Hannah's research will highlight the costs of premature mortality to individuals and society as a whole, which may have significant implications for how decision makers choose to allocate scarce resources. Hannah hopes her work will provide a valid method of incorporating societal costs into economic evaluations of health interventions and also that it will highlight the economic benefits of disease prevention.

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Thesis title: Statistical methods addressing biases and inefficiencies in the design and analysis of clinical trials

PhD candidate: Manjula Schou

Supervisor: Ian Marschner

Associate supervisor: Prof John Simes

Summary: Manjula's research project is studying a suite of problems concerning statistical methodology that can be used to address common biases and inefficiencies in the design and analysis of randomised studies, particularly clinical trials. Clinical trials methodology is one of the most important applications of statistics, and although it has been a widely studied area, many clinical trials are designed and analysed in either suboptimal or biased ways. The proposed research is seeking to address this in the following areas: adaptive methods involving analysis or modification of ongoing studies; subgroup analysis with particular reference to interpretation of heterogeneity in multinational studies; efficient study design in multi-arm trials; and study design methods that anticipate dropouts.

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Thesis title: Additive variance regression methods with application to measurement error models in clinical biomarker studies 

PhD candidate: Kristy Mann

Supervisor: Val Gebski

Summary: Kristy is developing new statistical methods for modelling the effects of covariates on measurement error in biomarker studies of cardiovascular disease, neonatal medicine and HIV. These models assess whether biomarker changes in response to new treatments are beyond what can be expected by chance, and whether they are related to patient-specific characteristics. Methodological complexities being considered include censoring, which arises when the biomarker measurement is outside the limits of detection of a laboratory assay, and truncation, when individuals are only enrolled in a study if their biomarker value is within a particular range, which leads to a biased distribution. As censoring and truncation are both aspects of missing data, an extension of the conditional expectation maximization (CEM) algorithm should be an ideal method for dealing with these complexities.

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Thesis title: Efficacy of pre-hospital management of severe head injury by physician teams rather than paramedics 

PhD candidate: Alan Garner

Supervisor: Val Gebski

Associate supervisor: Danny Cass

Summary: The Head Injury Retrieval Trial is a randomised controlled trial comparing the outcomes of patients with severe blunt head injury treated by physician prehospital teams compared with paramedic teams in the greater Sydney area.  The study will determine whether the advanced interventions that can be provided by the physician team are associated with lower mortality and disability at 6 months.   Patients included in the trial are adults (age greater than 15 years) likely to have a significant head injury identified from the emergency call information received by the NSW Ambulance computed assisted dispatch system.   A number of processes were developed specifically for the trial such as the case identification system and the physician dispatch and treatment models.  These will be the subject of additional evaluations in terms of effect on the prehospital trauma system in Sydney and the efficiency of operations.

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Thesis title: The contribution of obesity, inflammation and autonomic function to the vascular health of adolescents with diabetes

PhD candidate: Yoon Hi Cho

Supervisor: Prof Alicia Jenkins

Associate supervisors: Prof Kim Donaghue, A/Prof Maria Craig, A/Professor Hiran Selvadurai

Summary:   The aim of this project is to examine the role of subclinical autonomic dysfunction, obesity and inflammation/oxidative stress and in the early pathogenesis of vascular complications in adolescents with diabetes. This project will utilise novel technology and biomarkers, as well as established methods of assessing early markers of vascular complications in three distinct groups of diabetes in adolescents: primarily type 1 diabetes, but also type 2 and cystic fibrosis-related diabetes. Examining these earliest markers may identify a subpopulation at higher risk of vascular complications and elucidate potential pathways for early intervention, to optimise the clinical outcomes for young adults living with diabetes.

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Thesis title: Identifying molecular signatures that define insulin-producing cells

PhD candidate: Wilson Wong

Supervisor: Anand Hardikar

Summary: Insulin producing cells are not restricted to the pancreas, but are also found naturally occurring in the gallbladder as well as the brain.  Wilson is focussing on understanding the similarities and differences in insulin-producing cells from these 3 diverse tissues (pancreas, gallbladder and brain) by assessing the transcriptome, epigenome and protein expression of key pancreatic genes in these tissues.

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Thesis title: RNA-based Analysis for the Prediction of Islet Death: The RAPID Study

PhD candidate: Ryan Farr

Supervisor: Anand Hardikar

Summary: Ryan's work involves understanding the role of microRNAs as biomarkers of diabetes and complications.  His project involves profiling key microRNAs and other non-coding RNAs in several thousand patient samples. 

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Thesis title: Non-invasive detection of subclinical atherosclerosis in high risk groups

PhD candidate: Jason Harmer

Supervisor: David Celermajer

Associate Supervisor: Anthony Keech 

Summary: Jason's PhD studies focused on the detection of subclinical atherosclerosis and associations with risk factors for cardiovascular disease in a number of populations, using non-invasive methods such as vascular ultrasound. Studies were conducted in a cohort of young children, migrant S.E Asian Indians in Australia compared with rural Indians in Andhra Pradesh, and adults with diabetes mellitus. In the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, vascular substudies to understand the mechanisms for increased risk of cardiovascular disease in diabetes mellitus were included, and much of this thesis describes the results of these vascular substudies.  

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Thesis title: The significance of internal mammary node metastasis in breast cancer

PhD candidate: Farnoush Noushi

Supervisor: Andrew Spillane

Associate supervisor:Val Gebski

Summary: Farnoush aims to review the available evidence on the impact of internal mammary node (IMN) metastasis in breast cancer. Then will create predictive models/nomograms on the frequency IMN metastasis and their impact on survival from large epidemiological databases. Farnoush will assess the current trends in the evaluation and treatment of IMN nodes by oncologists and determine the need for improved methodologies for the evaluation of IMNs. Assess the false negativity in IM and axillary sentinel node biopsy and explore other methodologies and to model the survival impact of false negative sentinel lymph node biopsies.

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Thesis title: Advanced glycation end products and oxidative stress in diabetes and novel diabetes therapeutics

PhD candidate: Ben Ma

Supervisor: A/Prof Alicia Jenkins

Associate supervisor: Prof Darren Kelly, Dr Andrzej Januszewski

Summary: Advanced Glycation End-Products (AGEs) can promote diabetic complications and it is hypothesised that drugs with anti-AGE, anti-oxidant, anti-inflammatory or anti-fibrotic effects can reduce AGE levels and diabetic vascular complications. This project is specifically aimed at:
1. determining if six novel potentially anti-AGE drugs can reduce:
a) AGE formation in a glucose and methyl-glyoxal (MGO) incubated human albumin model
b) intracellular production of reactive oxygen species (ROS) from human aortic endothelial cells in the presence and absence of AGEs
c) vascular cell outgrowth from adult human arteries in the presence and absence of AGEs
2. characterisation of a novel mouse model with mitochondrial dysfunction, which could be utilized for future studies on AGEs and diabetic complications

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