Medicine and Health Sciences Commons^™

Quantifying The Heterogeneity Of The Immunoglobulin G N-Glycome In An Ageing Australian Population: The Busselton Healthy Ageing Study, Alyce Russell

Theses: Doctorates and Masters

The use of immunoglobulin G N-glycomics to study chronic non-communicable disorders and other complex phenotypes emerged following the Human Genome Project. The consortium discovered that most phenotypes were too complex to be explained by genetics alone. Thus, the biological importance of epigenetics was recognised; heritable modifications to gene expression rather than the genome itself. Nglycosylation is a form of epigenetic regulation known as a post-translational modification. It stabilises the immunoglobulin G structure and alters downstream responses elicited by the antibody and is extensively studied as a candidate biomarker in the post-genomic era.

The N-glycosylation of immunoglobulin G itself is complex, …

Dna Methylation Of The Clusterin Promoter: Associations With Alzheimer’S Disease Risk And Related Phenotypes, Madeline Peretti

Theses: Doctorates and Masters

Background

In 2017 approximately 50 million people worldwide were living with dementia. With Alzheimer’s disease (AD), accounting for 50-70% of dementia cases making this debilitating disease, with no current effective prevention, treatment or cure, a critical healthcare concern. Genome wide association studies (GWAS) have identified a number of risk genes for late onset AD (LOAD); Apolipoprotein E (APOE), a gene involved in the cholesterol/lipid pathway is considered the gene with the greatest risk. The third most associated AD risk gene is Clusterin (CLU), is also involved in the cholesterol/lipid pathway. CLU has been implicated in both …

Factors Affecting The Survival And Implantation Of Human Blastocysts Following Vitrification, Hamish Barblett

Theses: Doctorates and Masters

The increased cell numbers, presence of the blastocoel and rapid cell re-organisation have required the development of specific survival criteria post warm to effectively select the most viable blastocyst for transfer. Pre-freeze blastocyst expansion and post warm re-expansion have been shown to contribute significantly to the chances of an implantation and subsequent live birth. The aim of this study was to explore factors that influence the outcome of blastocyst transfers after vitrification and warming, and hopefully improve outcomes by further applying improvements in future cycles. Variables from 8 years of vitrified/warmed blastocysts were retrospectively compiled and analysed to determine the …

Chemical Composition And Toxicity Of Emissions From Burning Five Vegetation Types Of Western Australia Under Experimental Combustion Conditions, T T Trang Dong

Theses: Doctorates and Masters

This study investigated the emission factors (EFs) for inorganic gases (CO2, CO, SO2, NO and NO2), carbonyls (formaldehyde, acetaldehyde, acetone, propionaldehyde, butyraldehyde and benzaldehyde), volatile organic compounds (VOCs) and particulate matter (PM2.5 and PM10) from laboratory-based fires of vegetation from five typical vegetation types of Western Australia. Species burnt were three grasslands (Spinifex represented by Triodia basedowii, Kimberley grass represented by Sehima nervosum and Heteropogon contortus, and an invasive grass represented by Ehrharta calycina (Veldt grass)), Banksia woodland and Jarrah forest under different combustion conditions. Chemical composition (water-soluble metals and polycyclic aromatic hydrocarbons – PAHs) and in vitro toxicity …

The Cryopreservation Of Human Semen, And Subsequent Evaluation Of A Commercially-Available Device To Isolate Motile Sperm, Callum Andrew Robinson

Theses: Doctorates and Masters

The cryopreservation of human semen is a vital asset in assisted reproductive technologies (ART). Although advances have been in the freezing of sperm, further refinement is both necessary and ongoing. Computer-assisted semen analysis (CASA) has been increasingly utilised in both research and diagnostic however there are a range of variables that must first be controlled in order to produce reliable measurements. Following thawing, sperm must be isolated from both the original seminal plasma and the cryoprotectants; the two most used isolation methods include density gradient centrifugation (DGC) and the swim-up method.

The present thesis sought to investigate the following areas …

Circulating Tumour Dna: A Non-Invasive Biomarker For Melanoma, Ashleigh Cavell Mcevoy

Theses: Doctorates and Masters

Cutaneous melanoma accounts for 90% of all skin cancer deaths (Balch et al., 2010) and is responsible for 3.6% of deaths from cancer in Australia (Australian Institute of Health and Welfare, 2016). Whilst early detection and successful surgical removal of primary melanomas have improved survival rates (DeSantis et al., 2014), approximately 30% of these patients will have disease recurrence at some point in their lives (Soong et al., 1992; Soong et al., 1998). This is despite being considered disease free following treatment, which may have included surgical removal of the primary and/or its metastasis/es, radiation and/or systemic therapy. Whilst the …

Nurse Staffing, Patient Falls And Medication Errors In Western Australian Hospitals: Is There A Relationship?, Ahmad Mousa

Theses: Doctorates and Masters

Background: According to the Australian Bureau of Statistics (2013) falls and medication errors in hospitals are among the first twenty leading causes of death. Research on the relationship between nurse staffing, patient falls, and medication errors are limited. Even scarcer are studies that examine this relationship on a nursing shift by shift and ward by ward basis, and no research exists on shift overlap periods and adverse patient outcomes.

Objective: This study examined whether there was a relationship between hospital inpatient falls and medication errors and nurse staffing on a shift by shift and ward by ward basis, including an …

Human Oocytes And Embryos Viewed By Time-Lapse Videography, And The Development Of An Embryo Deselection Model, Yanhe Liu

Theses: Doctorates and Masters

Despite its wide application today, in vitro fertilization (IVF) treatment continues to have relatively low efficacy, largely due to inaccuracy in selecting the best quality embryo(s) from the cohort for transfer. Novel methodologies for improved selection are being developed, and time-lapse observation of human embryos is gaining increasing popularity due to the more detailed morphokinetic information obtained plus uninterrupted culture conditions. The morphokinetic information enables the use of quantitative timings in developmental milestones of embryos and qualitative measures of abnormal biological events, to assist embryo selection/deselection. This project aimed to identify current limitations in the use of such measures and …

The Association Between Environmental Cadmium Exposure And All-Cause Mortality And Cardiovascular Disease In A Cohort Of Elderly Western Australian Women, Kane Deering

Theses : Honours

Introduction: Recent research suggests an association between environmental cadmium exposure and increased risk of, and death from, cardiovascular disease, the number one cause of mortality in Australia and worldwide. However, the research to date is neither comprehensive nor have there been any studies conducted on an Australian population. This study identified whether increasing concentrations of urinary cadmium in elderly West Australian women was associated with an increased odds of incidence of, and deaths from CVD, as well as all-cause mortality.

Method: Cadmium excretion was measured in urine samples collected at baseline (1998) from 1359 women from Perth who …

Saying ‘No’: A Biographical Analysis Of The Experiences Of Women With A Genetic Predisposition To Developing Breast/Ovarian Cancer Who Reject Risk Reducing Surgery, Doreen Molloy

Theses: Doctorates and Masters

Background: Genetic technologies have identified some of the genes implicated in cancer susceptibility. Women with mutations in breast/ovarian cancer-susceptibility genes (BRCA1 and 2) have a lifetime combined risk of breast/ovarian cancer of more than 80%. Risk reducing surgery (RRS) reduces cancer risk by as much as 90% in high risk populations. Despite this, some BRCA1/2 mutation-positive women say no to RRS.

Purpose: To illuminate an understanding of why women at high risk of developing breast/ovarian cancer say no to risk reducing surgery (RRS).

Design: Denzin’s (1989) interpretive biography was combined with Dolby-Stahl’s (1985) literary folkloristic methodology to provide a contextualised …

The Clinical Utility Of The Halosperm Assay And The Development Of A Simplified Method Of Human Semen Storage For The Testing Of Sperm Dna Fragmentation, Ashleigh Cavell Mcevoy

Theses: Doctorates and Masters

Male infertility is typically diagnosed upon routine semen analysis following the World Health Organisation’s (WHO) semen analysis manual. Recent editions of the manual have essentially changed the diagnosis of a semen sample, prompting debate between experts as to which edition should be followed. Deoxyribonucleic Acid (DNA) integrity analysis is proving to be a useful adjunct to semen analysis as 15% of infertile men have a normal semen analysis but they have an increased DNA fragmentation level (DFL) which has been associated with increased disease incidence in any resultant offspring. However, such tests are not endorsed by the WHO, possibly due …

Plasma Insulin-Degrading Enzyme: Characterisation And Evaluation As A Potential Biomarker For Alzheimer's Disease, Michelle Tegg

Theses: Doctorates and Masters

Alzheimer’s disease (AD) is increasing in prevalence due to increasing lifespan and altered lifestyle. It is the fourth major cause of death in Western countries, resulting in significant economic and social impact (Von Strauss, et al., 1999; Goate, 1997). There are no blood biomarkers currently accepted for the diagnosis of AD, and the identification of suitable biomarkers would eventually reduce the necessity for invasive, expensive and slow diagnostic procedures, as well as facilitate prognostic studies. An AD blood test would decrease the need for delaying diagnosis due to ambivalent presentation, and allow therapeutic intervention to commence at an earlier …

Homebirth In Wa: Why Women Make This Choice, Colleen Ball

Theses: Doctorates and Masters

Background: Homebirths in Western Australia (WA) account for approximately 0.8% of all births. Two consecutive reports from the Perinatal and Infant Mortality Monitoring Committee found increased rates of perinatal mortality in homebirths and recommended a prospective cohort study to assess mortality and morbidity outcomes for women with planned home births in WA. The Homebirth in WA Study, of which this thesis is a component, has been funded by a directed research grant.

Aim: The aim of this study was to explore the specific reasons why women in WA choose homebirth. Research on homebirths is focused on perinatal outcomes and …

The Impact Of Implementing A Sudden Infant Death Syndrome Education Package In Jordan, Shereen Hamadneh

Theses: Doctorates and Masters

Background: Sudden Infant Death Syndrome (SIDS) is a problem worldwide. In North Jordan, SIDS rate was high as 1.32 per 1,000 live births and contributed 6% to the infant mortality rate (Bataineh, Shawagfeh, & Twalbeh, 2008). However, SIDS risk factors are preventable and can be reduced by improving knowledge and changing relevant behaviours of parents and healthcare providers (American Academy of Pediatrics, 2013; American SIDS Institute, 2011; Bataineh, Hussein Shawagfeh, & Twalbeh, 2008; Bredemeyer, 2004; Grazel, Phalen, & Polomano, 2010b; Moon, Oden, & Grady, 2004; NICHD, 2010). Still educating Jordanians about SIDS has not been a national health policy priority. …

Impact Of Nutrition On Cognition And Its Association With Blood And Brain Alzheimer Disease Related Biomarkers, Samantha Gardener

Theses: Doctorates and Masters

Alzheimer’s disease (AD), the most common form of senile dementia, currently affects over 35 million people worldwide. While there is no cure or effective treatment, early intervention programs hold considerable promise. Following particular dietary patterns represents one potential intervention strategy accessible to all.

Results from previous studies investigating the association of diet, cognition and biomarkers of AD are inconsistent: Positive results have been reported (1-7), whilst others have shown no associations. Prior to this thesis, no study has assessed the relationship of four dietary patterns to cognition, blood-based and neuroimaging biomarkers of AD in a large highly-characterised ageing cohort. Participants …

Biomarkers Of Disease : Concentrations In The Serum Of Women During Natural And Stimulated Ovarian Cycles And During Early Pregnancy, Melissa Stemp

Theses: Doctorates and Masters

Molecular biomarkers are chemical signatures that all cell types possess. They are used in medicine to evaluate both normal biological events and pathogenic processes. A series of biomarkers associated with cancer of the breast, ovaries and other parts of the female reproductive tract and the monitoring of pregnancy were measured in disease‐free women. The biomarkers measured were prostate specific antigen (PSA), CA125, CA15‐3, CA72‐4, and pregnancy associated plasma protein‐a (PAPP‐A). The patterns of change during natural and stimulated ovarian cycles and early pregnancy were investigated to determine if these biomarkers could reflect normal events relating to ovulation and implantation/placentation. In …

Pax3 Expression, Protein Modifications And Downstream Target Gene Profiling In Melanocytes And Melanoma Cells, Danielle Bartlett

Theses: Doctorates and Masters

PAX3 is a transcription factor. It plays a major role in the development of melanocytes in the embryo. As a result of alternative splicing, the gene gives rise to eight different transcripts which encode proteins that have differing structures and are therefore likely to activate different downstream target genes. The presence of post-translational modifications has also been shown to alter the functions of the proteins.

PAX3 regulates the maintenance of undifferentiated melanoblasts and mediates pathways involved in proliferation, migration and survival. It has been shown to be expressed in melanoblasts, adult melanocytes, naevi and in most melanoma cells. This implies …

Discovery Of New Biomarkers Of Mild Cognitive Impairment And Alzheimer's Disease Risk In Buccal Cells Using Laser Scanning Cytometry, Maxime Francois

Theses: Doctorates and Masters

Previous studies have shown that mild cognitive impairment (MCI) may reflect the early stages of more pronounced neurodegenerative disorders such as Alzheimer’s disease (AD). In clinical practice, patients with AD are not usually identified until the disease has progressed to a stage when primary prevention is no longer possible. Therefore there is a need for a minimally invasive and inexpensive diagnostic to identify those who exhibit cellular pathology indicative of MCI and AD risk so that they can be prioritised for primary prevention. Human buccal cells are accessible in a minimally invasive manner, and exhibit cytological and nuclear morphologies that …

Investigating The Impact Of Cd147 And Its Expression On Neurodegenaration And Alzheimer's Disease (Ad), Limbikani J. Kanyenda

Theses: Doctorates and Masters

CD147, also known as basigin, extracellular matrix metalloproteinase inducer, neurothelin, tumour cell-derived collagenase stimulatory factor, M6, HT7, OX47 or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues with high expression in the hippocampus, pre-frontal cortex, thyroid, heart, early erythroid, amygdala and placenta. This protein is involved in various cellular and biological functions such as lymphocyte migration and maturation, tissue repair, cancer progression, T and B lymphocyte activation and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with with cyclophilin A, cyclophilin B, sterol carrier protein, caveolin-1 and integrins, and …

Internet Use And Its Impact On Secondary School Students In Chiang Mai, Thailand, Kesaraporn Wanajak

Theses: Doctorates and Masters

Internet addiction (IA) is a relatively new field of academic inquiry. Empirical studies suggest that IA, like other well researched addictive behaviours, has an effect on many aspects of a person‟s life, including academic/work performance, relationships, and physical and mental health (Goldberg, 1996; Young, 1996, 1998). Evidence of IA has been suggested by the findings that some Internet users spend increasingly longer periods of time online and experience withdrawal symptoms when offline. Those preoccupied with Internet-related activities may neglect exercise, family and social activities (Kim et al., 2010; Nalwa & Anand, 2003; Seo, Kang, & Yom, 2009; S. Yang & …

Yeast As A Model For Studying Aβ Aggregation, Toxicity And Clearance, Prashant R. Bharadwaj

Theses: Doctorates and Masters

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder of the central nervous system, characterised by acute memory loss and behavioural symptoms. The AD brain is characterized by the presence of senile amyloid plaques associated with degenerating neurites and inflammatory processes. The major protein component of these amyloid deposits is the amyloid beta (Aβ) protein. The Aβ protein is a 40 or 42 amino acid cleavage product of APP (Amyloid Precursor Protein) which is produced in low levels in the normal ageing brain. Although senile amyloid plaques is the major pathological hallmark of AD brains, accumulating evidence has been presented to …

Impact Of Static Stretch And Muscular Contractions On Force Production Within The Human Triceps Surae Muscle-Tendon Complex, Anthony D. Kay

Theses: Doctorates and Masters

Pre-performance routines commonly include stretching and intense muscular contractions in an attempt to optimise muscular performance and reduce injury risk. However, the isolated and combined effects of stretching and muscle contractions on neuromuscular performance are not well described. The aims of this research were to examine the effects of acute static stretch and intense muscular contractions on force production of the human plantarflexors and to examine possible mechanical and neuromuscular mechanisms underpinning any changes. Techniques including isokinetic dynamometry, electromyography (EMG), sonography and motion analysis were used in three studies on recreationally active human volunteers (n=20). In the first study, three …

Metabolomic Investigation Of A New Rat Model Of Autosomal Recessive Polycystic Kidney Disease, Hayley White

Theses : Honours

Metabolomics is complementary to genomics, transcriptomics and proteomics; however, it has the capacity to reflect the activities of the organism at a functional level. Metabolomics can therefore be used as a diagnostic tool by identifying the up- or down-regulation of metabolites in the cell, tissue, plasma, serum or urine. Specifically, these are, but are not limited to, identifying biomarkers of disease, monitoring drug treatments, and monitoring surgical procedures such as organ transplant. Autosomal recessive polycystic kidney disease (ARPKD) makes up 5-8% of patients requiring kidney dialysis and/or transplantation and of these, an estimated 50% of patients progress to end-stage renal …

The Evaluation Of Midazolam On Head Injured Patients In The Prehospital Setting, Dragana Klinac

Theses: Doctorates and Masters

Midazolam (Hypnovel ®) is the only sedating agent used by paramedics at St John Ambulance Service W.A. in the management of many conditions including seizure activities, antisocial or uncontrollable behaviours, back pain incidents and head injuries. Midazolam, with a rapid absorption, fast onset of action and short duration on neurological activity, has been accepted as a safe and effective agent in prehospital treatment since the late-1990s. Often, if a patient is not complying with treatment or is uncontrollable or aggressive, paramedics are required to sedate the individual. This study primarily examines the use of midazolam for the sedation of unmanageable …

The Effect Of Antioxidant Supplementation On Human Sperm Cryopreservation, Katrina E. Taylor

Theses : Honours

Semen cryopreservation has an important role in assisted reproductive technology however, the cooling, freezing and thawing processes often result in a significant loss of sperm motility, viability and nuclear integrity. The destructive effects of cryopreservation are significantly exacerbated in samples exhibiting low sperm number and poor morphological characteristics. Recent research into infertility has focused on the correlation between excessive oxidation and subfertility, in particular radical induced lipid peroxidation within the phospholipid bilayer of the spermatozoon plasma membrane and the promotion of cellular damage as a result of antioxidant insufficiency. The aim of this study was to evaluate the effect of …

Analysis Of Expression Patterns Of Scl And Pax7 In The Mouse Brain For Potential Concomitant Function Within The Mesencephalon, Julie Stampalia

Theses : Honours

Investigation of the cascade of events that leads to brain formation during embryogenesis allows an understanding of the processes involved that may well be applicable to future neurodegenerative therapies. Two genes at work during embryonic neurogenesis in a brain region called the superior colliculus are Scl, a member of the basic helix-loop-helix factor transcription factor family and Pax7, a paired box transcription factor containing a homeobox dornain. The superior coiliculus forms part of the visual system in mammals and in sepmate studies both the Scl and Pax7 genes have been shown to be present in this region of the mouse …

Molecular Genetic Investigation Of Autosomal Dominant Hemifacial Microsomia, Rebecca Watt

Theses: Doctorates and Masters

The overall purpose of this project was to explore the underlying pathogenesis of Hemifacial microsomia (HFM), investigate treatment and management options identify likely candidate genes and screen candidate genes for mutation(s) causing the form of HFM segregating on chromosome 11 in a West Australian family. Hemifacial microsomia is a congenital malformation arising from the derivatives of the first and second branchial arches. It is both clinically and genetically heterogeneous and can occur sporadically or segregate within families in an autosomal fashion. HFM is characterised by significant undergrowth to one side of the face and is a common birth defect with …

Target Selection For Antisense Oligonucleotide Induced Exon Skipping In The Dystrophin Gene, Stephen J. Errington

Theses: Doctorates and Masters

Duchene Muscular Dystrophy (DMD), and the milder allelic Becker muscular dystrophy (EMD), are X-linked recessive muscle wasting disorders characterised by mutations in the dystrophin gene. DMD occurs at a frequency of approximately 1 in 3500 male newborns and life expectancy is typically less than 30 years. Due to progressive muscle wasting, affected boys are restricted to a wheelchair by the age of 12 years. The most common cause of death is pneumonia, compounded by cardiac involvement. Mutations that disrupt the dystrophin reading frame, or prevent the synthesis of either terminus, preclude the synthesis of a fully functional dystrophin. The subsequent …

Good Life In The Balance: A Cross-National Study Of Dutch And Australian Disability Perspectives On Euthanasia And Physician-Assisted Suicide, Erik A. Leipoldt

Theses: Doctorates and Masters

This is a cross-national qualitative study with the purpose of obtaining perspectives held by people with quadriplegia and leading figures in disability movements in the Netherlands and Australia on the issues of euthanasia and physician-assisted suicide (EPAS). A disability voice is not prominent in public debate on EPAS in Australia or the Netherlands, even though people with disabilities are often thought to be vulnerable in relation to EPAS policies. Disability perspectives are potentially valuable in illuminating issues in relation to euthanasia and physician-assisted suicide, because issues of dependence, independence, and individual autonomy play important roles in relation to both EPAS …

Molecular Genetic Investigation Of Autosomal Dominant Muscular Dystrophy, Christopher Meredith

Theses: Doctorates and Masters

This thesis contributes to the Human Genome Project by adding detail to the physical and genetic maps of the human genome, and by identifying a strong candidate gene for a form of distal myopathy. Genomic clones for the human skeletal muscle genes slow troponin (TNN/1), alpha actin (ACTA1), and (3-tropomyosin (TPM2) were isolated for use in the fluorescent in situ hybridisation localisation of these genes on the cytogenetic map of the human genome. The localisation of these genes made them potential candidates for inherited skeletal muscle diseases, including the muscular dystrophies investigated here. Microsatellite, VNTR and RFLP markers were used …