3,899 results for Thesis, ResearchSpace@Auckland

  • Evaluation of utilisation of the Prevention of Mother-to-Child Transmission of HIV Programme in Central province, Kenya

    Ngugi, Catherine Njeri (2013)

    Masters thesis
    The University of Auckland Library

    Background: The PMTCT HIV programme has been one of the most successful HIV preventive interventions towards HIV-free future generations. However, even though the programme is virtually effective in developed countries, many developing countries are reporting child HIV infections due to the MTCT. The programme has existed in Kenya for more than a decade, yet in 2011, 12,894children were HIV infected due to MTCT Objective: To evaluate the PMTCT programme, especially the HIV testing from the antenatal period to the postnatal period among expectant parents attending Nyeri Provincial General Hospital in Central Province, Kenya. Design: Retrospective analysis of the hospital registers. Methods: Three hospital registers were analysed for the period from July 2009 to September 2012. The registers were for antenatal, intrapartum and postnatal care respectively. Each register documented the utilisation of PMTCT services by the expectant parents. Descriptive and inferential statistics were produced to analyse data from the registers. Results: The PMTCT services utilisation was sub-optimal. Of the 504 expectant mothers who attended the antenatal clinic, 59.9% came once, 80.4% had their first visit in the third trimester (between weeks 28 and 40) and only 6.9% were accompanied by their partners. All the women were HIV tested in their first visit but only 12.1% were rescreened after three months, and only 3.8% had been tested prior to the current pregnancy (p=0.000). No expectant mother was tested for HIV intrapartum or postpartum. The children of the 504 mothers who were HIV tested were those whose parent/s were known to be HIV positive or who had presented to a child welfare clinic with recurring symptoms suggestive of a failing immune system. Conclusion: Public health programs need to strengthen the PMTCT and HIV prevention programmes to ensure that HIV testing preconception and in pregnancy is fully implemented and strengthened, alongside continued education of the public through community programmes and the media. To avert further horizontal and vertical transmission of HIV, there is a need to address urgently the identified missed opportunities in the PMTCT program. These programmatic challenges require health system redesign and strengthening, resource allocation, addressing research gaps and reassessing the current PMTCT policies.

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  • Studies on the Oxidation of Aromatic Steroids

    Manning, Terence David Ross (1968)

    Doctoral thesis
    The University of Auckland Library

    This thesis is concerned primarily with a study of the oxidation of aromatic steroids employing either chromium trioxide-aqueous acetic acid or chromium trioxide-aqueous sulphuric acid-acetone mixtures. The nature of the chromic acid oxidation of various functional groups is discussed first and this is followed by an outline of the two methods used for the synthesis of the aromatic steroids which were oxidised in this study. The second part of the discussion deals with the oxidation of these aromatic steroids. It was found that chromic acid oxidation of ring-A aromatic steroids containing a strong electron-donating C3-substituent, such as methoxyl, gave the corresponding 9-hydroxy-11-oxo derivative (ketol). However, a ketol was not formed if a C3-methoxyl substituted ring-A aromatic steroid also contained a substituent at C1. When a C3-methoxyl substituent was present, the 6-oxo-ring-A aromatic steroid was a minor oxidation product but such compounds were the major products from the chromic acid oxidation of ring-A aromatic steroids containing a weak C3-electron-donating group, such as acetoxyl. The oxidation of a ring-A aromatic steroid containing a C2-methoxyl substituent gave an almost quantitative yield of the corresponding 6-oxo compound. Suzuki103 has claimed that the major oxidation product of 17β-acetoxy-3-methoxyestra-1,3,5(10)-triene (34b) is 17 β-acetoxy-9α- hydroxy-3-methoxyestra-1,3,5(10)-trien-11-one (123). Physical and chemical evidence are presented to show that this product is in fact the 9β-hydroxy epimer and a reaction pathway for its formation is proposed. An examination of the oxidation products of a ring-B aromatic steroid and a ring-C aromatic steroid shows that no ketols were formed.

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  • Development of conducting polymer-based antioxidant packaging materials

    Hsu, Chyong Fang (2009)

    Doctoral thesis
    The University of Auckland Library

    Antioxidants are commonly used as preservatives for protecting foodstuffs from oxidation. Packaging is believed not only to increase the economic value of products but also improve their qualities. Conducting polymers (CPs), such as soluble polyaniline and soluble polypyrrole, have been reported to exhibit antioxidant activity. Development of conducting polymer containing packaging materials, with antioxidant properties, is therefore the focus of this project. Polypyrrole (PPy), polyaniline (PANI) and poly (3,4-ethylenedioxythiophene) (PEDOT) powders were prepared using various amounts of the oxidant ammonium persulfate (APS). Spectroscopic methods, including IR and Raman, were used to identify the structures of the CP powders synthesized at various APS levels. It was found that a high level of APS led to overoxidation of the CP powders. The conductivity and doping level of the CP powders formed using higher concentrations of the APS oxidant were found to be lower than those prepared using low concentrations of APS, which might be due to overoxidation, damaging the CP structures during the preparation processes. The antioxidant activity of PPy, PANI and PEDOT powders were evaluated using the DPPH and ABTS assays. The results showed that CP powders synthesized at a high concentration of APS presented lower free radical quenching effects, likely also due to overoxidation. The optimum initial ratio of APS to monomer for the synthesis of CP powders with a superior DPPH free radical scavenging was found to be around 0.5 for PPy, 1.5 for PANI and 1.0 for PEDOT, and the antioxidant ranking of the CP powders was as follows: PANI1.5 > PPy0.5 > PEDOT1.0. The reduced forms of PPy, PANI and PEDOT exhibited better radical scavenging abilities than the as-prepared powders. PANI nanotubes, synthesized at high pH, was also found to exhibit stronger free radical scavenging activity than the regular granular PANI formed under acidic conditions. Structural changes of PANI powders after reaction with free radicals were observed in IR and XPS spectra, showing an increase in the ratio of imine (C=N) to amine (C-N) units. PANI EC films were prepared using a solution method and the antioxidant capacity of the PANI EC films are examined using the ORAC assay. The results showed efficient peroxyl free radical scavenging activity of the PANI EC films. A very good correlation between the ORAC response and the area of tested film was also observed, indicating a homogenous dispersion of active PANI powder across the film. Similar to the results obtained from the DPPH and ABTS assays, reduced PANI presented greater peroxyl radical scavenging activity than the as-prepared powders. The influence of the PANI EC films on the oxidation of Ropufa oil was determined by peroxide value (PV) measurement. After incubation at 60oC for several days, the oil stored in the presence of the PANI EC film was found to exhibit a lower PV than in the absence of a CP film, indicating that the conducting polymer is effective in inhibiting oxidation of fish oil.

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  • Cerebral blood flow velocity variability in very low birthweight infants

    Coughtrey, Heather (2002)

    Doctoral thesis
    The University of Auckland Library

    Short-term variability in cerebral blood flow velocity (CBFV) in the VLBW infant largely relates to respiratory influence. Extreme variability may be a poor prognostic indicator. Few have studied cohorts of babies in this regard. I sequentially studied a consecutive cohort of unselected VLBW infants, to determine the frequency of respiratory influence on CBFVV and to identify factors associated with its occurrence. Doppler CBFV, arterial BP and respiratory signals were recorded simultaneously and spectral analysis was applied to identify a respiratory signal in BP and CBFV traces. Respiratory associated variability was present in the cerebral circulation at some time in more than half of the infants studied and was most likely in those of lowest gestational age who were hypotensive. Mortality, and cerebral morbidity as assessed by cerebral ultrasound were more common in those demonstrating a respiratory influence in CBFV. There was a strong correlation between the coefficient of variation(CV%) of BP and that of CBFV. Babies demonstrating hypotension had higher CV%s in CBFV; those who did not survive showed higher variability than survivors, but there was a wide spread of values in both groups. where the variability in CBFV was high, correlation between CBFV and BP was greater. However, no significant association was found between CV% of CBFV and brain injury, ductal patency, or sedation. Although exaggerated beat-to-beat variability in CBFV was an adverse prognostic indicator, absence of variability carried the worst prognosis. Slow variations of cerebral blood flow velocity at a frequency of 1-5 cycles per minute, previously described as a normal phenomenon, were also examined. Evolution of this variability was studied amongst those present for a month or more. Slow variations diminished with both increasing postnatal and postconceptional age, perhaps representing maturation of the balance between the two components of the autonomic nervous system. The cycle length of the slow variations was variable suggesting the presence of several low frequency components; longer recordings would be needed to resolve these. Addition of serial Doppler measurements of CBFV performed in the first week of life, did not improve prediction of an 18-month outcome obtained from ultrasound imaging alone.

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  • A framework for annotating and visualizing cellML models

    Wimalaratne, Sarala M. (2009)

    Doctoral thesis
    The University of Auckland Library

    The Physiome Project was established to develop tools for international collaboration and sharing physiological knowledge in the form of biological models and experimental data. The CellML language was developed in response to the need for a high-level language to represent and exchange mathematical models of biological processes. The language provides a flexible framework for describing the dynamics of biological processes but does not explicitly lend itself to capturing the underlying biological concepts such as the entities and processes that these models represent. The relationship between the biological process and the mathematical model describing the biological process is also often complex. This makes it difficult to see the biological concepts which the CellML structures represent. A framework which supports visualizing the biological concepts and its relationship to the underlying CellML model would provide a very useful toolset for understanding the biological concepts modeled in CellML. The CellML models need to be annotated with biological concepts in order to provide the machine interpretable data for generating a visual representation. We have developed an ontological framework which can be used to explicitly annotate CellML models with physical and biological concepts, a method to derive a simplified biological view from the annotations, a visual language for representing all biophysical processes captured in the CellML models, and a method to map the visual language to the ontological framework in order to automate the generation of visual representations of a model. The proposed method of model visualization produces a result that is dependent on the structure of the CellML models which requires modelers to structure the model in a way that best describes the biophysical concepts and abstractions they wish to demonstrate. Our argument is that this leads to a best practice approach to building and organizing models. As a part of this research, a software tool for visualizing CellML models was developed. This tool combines the visual language and the ontologies to generate visualizations that depict the physical and biological concepts captured in CellML models and enables different communities in diverse disciplines to more easily understand CellML models within the biological domain they represent. As research continues, with further improvement to the framework it would be possible to visually construct composite CellML models by selecting high level biological concepts.

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  • Does Māori Representation Matter?: an analysis of the relationship between Māori descriptive and substantive political representation in parliament and local government

    Summersby, Kim Margaret (2009)

    Doctoral thesis
    The University of Auckland Library

    This thesis investigates the relationship between Māori descriptive and substantive political representation in New Zealand’s parliament and local government. The 1993 parliamentary electoral reforms and optional changes to the structure of local body elections in 2001-02 aimed, in part, to help increase Māori descriptive representation. The overall number of elected Māori representatives in parliament has grown, and the proportion of Māori representatives in local government could increase should electoral reforms be implemented. Consequently, arguments based on democratic justice and equality for ensuring an adequate Māori political presence are being superseded by questions of who Māori MPs and Māori local councillors represent, and whether these representatives are making a difference in politics. This study examines the extent to which elected Māori representatives feel a specific responsibility to represent Māori and the ways Māori substantive representation is manifested. It also considers how institutional arrangements and attitudinal factors constrain or facilitate the promotion of Māori interests. This thesis presents case study analyses of Māori substantive representation based on in-depth interviews with elected Māori representatives. It is supported by an examination of three specific issues relevant to parliament, to help demonstrate how Māori MPs react and respond to issues of importance to Māori. The evidence suggests elected Māori representatives generally feel a specific responsibility to act for Māori interests within and outside their electorate’s geographic boundaries. The data demonstrates that whakapapa influences the perceptions elected Māori representatives have of their role in terms of substantive activities and style of politics. However, electoral system influences, political party practices, the type of representation provided by Māori, the proportion of Māori actually elected to a governing body and non-Māori attitudes to Māori issues, are salient to Māori substantive representation because they mediate the role of the representative. While the relationship between ‘standing for’ Māori and ‘acting for’ Māori interests is not directly correlated, this thesis suggests elected Māori representatives largely do promote Māori interests. Māori ethnicity influences the role of Māori MPs and councillors. Thus, Māori representation matters. This research adds to current understandings of the nature of Māori political representation and of New Zealand’s representative democracy.

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  • Studies of malnutrition in patients with inflammatory bowel disease

    Christie, Peter Michael (1990)

    Doctoral thesis
    The University of Auckland Library

    Patients suffering from Inflammatory Bowel Disease (IBD) as a group uniformly suffer from nutritional problems. Nevertheless the extent, severity and clinical significance of Protein Energy Malnutrition (PEM) in the various clinical presentations of these diseases remains unclear. In particular little is known of the nutritional status of the ambulatory patient with IBD. Confusion still exists over the long term nutritional changes following colectomy for colitis. Whether intravenous nutrition (IVN) should be prescribed in patients admitted to hospital for acute exacerbations of IBD still remains contentious. Recent work suggests that the significance of PEM relates to the associated impairments seen in various organ systems eg., impaired respiratory muscle function. Furthermore, there is other data to suggest that nutritional therapy may result in improvement in some of these physiological functions long before there is any measured change in the patient’s nutritional status. Through direct measurements of Body Composition (by neutron activation analysis in conjunction with tritium dilution) together with tests of physiological function (hepatosecretory proteins, skeletal muscle function, respiratory muscle function, wound healing and psychological function) work has been directed to clarify the following clinical questions:- 1. How extensive is the problem of protein depletion in the various clinical presentations of IBD? 2. What are the long term changes in body composition following surgery for colitis? and what is the nature of this restorative process. Is there a return to normal body composition? and if so, What is the duration of this recovery process? 3. What are the effects of a short course of IVN in patients suffering severe exacerbations of IBD? The results of these clinical studies have reaffirmed the high incidence of PEM in patients suffering from acute exacerbations of IBD, furthermore this work has established the existence of persisting protein deficits in the ambulatory patient with IBD who is in clinical remission. Contrary to previous reports, fully convalescent patients following surgery for colitis, were found to have normal body stores of protein and water. The timing of this restorative process was found however to take many months. A 2 week course of IVN was found not only to prevent further loss of body protein in a group of patients presenting with severe exacerbations of IBD, but also within a few days (4 days) lead to a significant improvement in hepatosecretory function, respiratory muscle function, skeletal muscle function, wound healing and psychological function. The magnitudes of these improvements although not complete was probably significant clinically. Following these early improvements, subsequent improvement was slow over many months and was dependent on an increase in body stores of protein.

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  • Pharmacology of morphine and the active metabolite morphine 6-glucuronide : a comparison of pharmacological and clinical effects

    Thompson, Paul Ivan (1991)

    Doctoral thesis
    The University of Auckland Library

    Morphine is an effective potent analgesic. However the side effects of nausea, constipation and sedation are seen frequently. Respiratory depression is not such a common problem clinically but is the most potentially dangerous toxicity. An analgesic inducing equivalent analgesic potency without these toxicities would be particularly valuable. Morphine 6-glucuronide (M6G), one of the major metabolites of morphine, has analgesic activity in animals and animal studies have suggested an improved therapeutic index. The initial study in this thesis confirms the analgesic activity of M6G in man and the pharmacokinetic profile after intravenous and oral administration has been determined. The elimination half life is approximately 1.6 hours with the rate of clearance closely correlating with creatinine clearance. Oral bioavailability at approximately 5%, however, is poor due to its hydrophilic nature. In an effort to more critically examine the comparative emetic potency of M6G and morphine, both compounds were administered to the ferret, a known emetic model for man. Surprisingly M6G had a greater emetic potency in this model. A pilot pharmacokinetic study performed on the ferret revealed that M6G is only a very minor metabolite accounting for approximately only 1% of the metabolic product of morphine compared to 10% in man. It is possible that other aspects of opiate handling are also different, and reminds us of the importance in studying the drug handling of any animal model used for the testing of any drug, particularly when metabolites are thought to play a role in clinical effect. No patients or volunteers in the initial open studies in man experienced any nausea or sedation. This observation prompted a double-blind randomized study comparing the analgesic potency, respiratory depression, nausea and sedation induced by morphine and M6G in normal volunteers. This study confirmed that M6G has an increased analgesic potency in man when compared to morphine and causes significanctly less respiratory depression, nausea and sedation. It has been previously hypothesized that the µ opioid receptor with lower affinity for morphine, the µ2 receptor, is responsible for the majority of morphine toxic side-effects, including respiratory depression. The last study presented in this thesis utilises radioligand binding studies to determine the opioid receptor binding affinities of morphine and M6G at the µ1, µ2, total µ and delta opioid receptors. This reveals that M6G has a 5-fold lower binding affinity to the putative µ2 opioid receptor and hence provides a possible explanation for the decreased toxicity seen compared to morphine. In light of the findings in man above, further investigation of this active morphine metabolite is therefore indicated as M6G could prove particularly beneficial to those patients with severe underlying pulmonary disease and for obstetric use.

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  • Epidemiology of asthma and bronchial hyperresponsiveness in Auckland children

    Pattemore, Philip Keith (1991)

    Doctoral thesis
    The University of Auckland Library

    Restricted Item. Print thesis available in the University of Auckland Library or available through Inter-Library Loan. In New Zealand (NZ) asthma mortality rates are higher than in any other developed country studied, and hospital admission rates for asthma are among the highest. Within NZ, both mortality and hospital admission rates for asthma are higher among Polynesians than among Europeans. To investigate the possibility that these differences were due to differences in asthma prevalence, a study was initiated to measure the prevalence and severity of asthma among both Europeans and Polynesians in Auckland using methods identical to those used in an overseas study. From all primary schools in the Auckland Urban Area, classes were sampled by two-stage, random, stratified sampling. In the winter of 1985, the children in the sampled classes were studied employing a questionnaire and a rapid, portable method of bronchial challenge testing with histamine which had been used to study schoolchildren aged 8 to 10 years in two areas in New South Wales (NSW), Australia. Participation was 83%, the participants comprising 1084 European, 509 Maori, and 460 Pacific Island children, who were closely matched in gender and age to the NSW children. Prevalence of various items was compared including asthma symptoms, diagnosed asthma, and bronchial hyperresponsiveness (BHR), defined as a 20% fall in the one-second forced expiratory volume (FEV1), on or before the administration of a cumulative dose of 7.8 µmol histamine. The prevalence rates of respiratory symptoms, BHR, severe BHR and BHR combined with symptoms were similar among the 1084 Auckland European children and 769 inland NSW children, but lower among 718 coastal NSW children than the other two sites. In Auckland, the prevalence of respiratory symptoms was higher in Maoris than among Europeans or Pacific Islanders, whereas prevalence of diagnosed asthma was similar in all three groups. Europeans had the highest rate of BHR and severe BHR followed by Maoris then Pacific Islanders. Maori and Pacific Island children reporting symptoms were less likely to receive prophylactic medication than European children. The study design also enabled assessment of the epidemiological correlates of BHR, which had been little studied in random populations before 1985. Among the Auckland children, bronchial responsiveness was found to be unimodally distributed, with no clear separation between children with a diagnosis or symptoms of asthma and those without. The presence or absence of BHR did not accurately identify children with a diagnosis or symptoms of asthma. A l4-variable multiple logistic regression model was developed which explained 27% of the variability in BHR rates. The main variables independently increasing BHR risk were: low baseline FEV1, a history of wheeze, diagnosed asthma, atopic conditions, or bronchodilator treatment, and European (as opposed to Polynesian) ethnicity. Climatic conditions at the time of the test were less strongly associated. In summary, neither the international nor the inter-ethnic differences in asthma mortality and asthma admission rates were adequately explained by differences in the prevalence of asthma symptoms, diagnosed asthma or BHR; however, differences in asthma severity and in the management of asthma may be contributory. In this large population-based study of children, BHR was associated independently with a number of different variables but did not precisely identify children reporting asthma symptoms or a diagnosis of asthma. Thus a single bronchial challenge test is not an ideal tool on its own for diagnosing asthma or measuring asthma prevalence.

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  • Use of analgesic agents in scoliosis surgery : the implications for spinal cord monitoring

    Loughnan, Bernadette Ann (1993)

    Doctoral thesis
    The University of Auckland Library

    Restricted Item. Print thesis available in the University of Auckland Library or may be available through Inter-Library Loan. The thesis examines the use of local analgesics as part of the anaesthetic technique for scoliosis surgery. Any agents used must have minimal interference with monitoring of spinal cord integrity. The literature on the anaesthetic requirements for scoliosis surgery is reviewed and the various methods of monitoring spinal cord function are discussed. The historical background and experimental rationale for the use of the somatosensory evoked potential (SEP) in scoliosis surgery is examined. The advantages of the epidural SEP over the scalp-recorded SEP are demonstrated. Spinal cord monitoring at many UK centres consists of measuring the SEP recorded from the C7 – T1 epidural space to stimulation of the posterior tibial nerve (PTN) at the popliteal fossa. The effects of a lumbar epidural injection of different local analgesic solutions on the SEP to posterior tibial nerve stimulation were investigated. In the initial study, epidural lignocaine 2% l0 ml was evaluated. The next two experiments assessed the changes after epidural diamorphine 0.1 mg kg-1 and epidural etidocaine 1% 10 ml respectively on the SEP. The final study compared the effects of epidural bupivacaine 0.25%, 0.5% and 0.75% l0 ml on the SEP. These studies showed that l0 ml of lignocaine 2%, bupivacaine 0.5% or bupivacaine 0.75% depressed significantly the epidural SEP. Diamorphine 0.1 mg kg-1 had no measurable effect. Etidocaine 1% caused a profound decrease, and in some cases an obliteration of the SEP. There was a clear concentration-dependent effect of increasing concentrations bupivacaine on the SEP. The effects of the different local analgesic agents on the neurophysiological variables are considered in the light of their known physicochemical properties. The literature on the neural generators of the epidural SEP is reviewed. My studies are compared to similar experiments on the scalp-recorded SEP and the SEP to dermatomal stimulation. Possible differences in the epidural SEP between scoliosis and non-scoliosis patients are noted. The possible relevance of the changes in mean arterial pressure when assessing alterations in SEP is examined. Etidocaine, and local anaesthetics of high lipid solubility, have no place in anaesthesia for scoliosis surgery. Furthermore, lignocaine 2%, bupivacaine 0.75% or bupivacaine 0.5% cannot be recommended because they interfere with monitoring of the SEP in the perioperative period. However, lower concentrations of bupivacaine such as 0.25%, together with diamorphine 0.1 mg kg-1, may be appropriate, since they have minimal effects on the SEP.

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  • Epidemiology of motor neuron disease in Scotland, 1989-90 : a prospective study of incidence, clinical features and prognosis, and incorporating a case control study of antecedent environmental factors

    Chancellor, Andrew Martin (1992)

    Doctoral thesis
    The University of Auckland Library

    Chapter 1 The part that 19th century Edinburgh medicine played in formulating the early concepts of motor neuron disease as a nosological entity is described, including some hitherto unrecognized descriptions by graduates of Edinburgh Medical School, including the first description of progressive bulbar palsy. Credit is given to the great European neurologists, especially charcot’s landmark contribution of the definitive clinico-pathological correlations. Terminology relating to MND is discussed and the problems which have arisen over the nosology relating to diseases of motor neurons. The requirement for a clearly defined classification system and the importance of measuring incidence in this disease are outlined. Chapter 2 A comprehensive review of previous studies of incidence, mortality and distribution is presented. It is suggested that the value of previous clinical descriptions and epidemiological studies of motor neuron disease (MND) have been limited by methodological problems. There appears to have been a real increase in mortality from MND over recent decades. Comparison of incidence in different places is complicated by non standardised methods of case-ascertainment and diagnosis but evidence is presented which challenges the traditional concept that the distribution of MND in developed countries is uniform and static. It remains uncertain, from the evidence available, if age specific incidence continues to rise into old age and the apparent “peak” in late-middle life is due to ascertainment bias. This is an important consideration on which to base aetiological hypotheses. In the northern hemisphere there is a weak positive correlation between standardised, age specific incidence and distance from the equator. There is a high prevalence focus of an atypical MND/ALS on Guam, and while an environmental factor is probably responsible, its nature is uncertain. The relevance of other reported clusters of MND is discussed and the requirements for the ideal study of MND incidence are outlined, which acted as the impetus for the Scottish Motor Neuron Disease Register (SMNDR). Chapter 3 The methodology of the SMNDR is described. This is the first collaborative, population based, prospective, epidemiological study of MND and illustrates the feasibility of such a study and the way in which Scotland is suited (in terms of size and National Health service structure) to such a project. Diagnostic criteria are outlined for application to this and other large scale studies. Of 257 patients registered with the SMNDR as possible MND diagnosed in 1989 and 1990 in Scotland, 229 with proven (by autopsy), clinically definite or probable, sporadic or familial MND, form the basis of the description of incidence, distribution, clinical features and natural history contained in this chapter. The crude incidence was 2.24/100,000/year and age specific incidence continued to rise steeply with age into the very elderly age bands. No evidence for clustering on the basis of Scottish regions was found. 5% of patients had a family history of MND; the clinical pattern varied according to sex and age, with elderly women most likely to present with, or develop, progressive bulbar palsy. Chapter 4 The utility of the 1989-90 Scottish Hospital In-patient statistics (SHIPS) and 1989-90 death certificate coding (Registrar General for Scotland) by International classification of Diseases (ICD)-9, 335 (MND) are analysed as a tool for epidemiological studies and heath care planning. Coded hospital discharge data were an inaccurate record of a diagnosis of MND with a positive predictive value of a diagnosis of MND as determined by SHIPS of 70%. Such data cannot, in their present form, be used as a reliable measure of incidence in Scotland. Greater care is required in the preparation of summaries and coding if these data are to be useful care planning and epidemiological research. However, as an important source of case notification for the SMNDR to achieve a complete sample of patients. There was also a problematic false positive rate (10%) for mortality data but this source more closely approximated true incidence. Chapter 5 A review of previous case control studies of environmental risks for MND is presented. In order to test the hypothesis that certain environmental factors may play a role in the aetiology of MND, a case control study of 103 incident patients (diagnosis date May 1990-october 1991; 57 from the above cohort (as described in chapter 3) and 46 diagnosed in 1991, age and sex matched with community controls was conducted and is described. Measures were taken to minimise potential sources of bias and these are discussed. Fractures were more common in patients than controls especially in the in the five years prior to symptom onset (odds ratio = 15 (95% CI, 2.3-654). Manual workers were over represented and a number of environmental exposures of potential toxicity including exposure to lead (OR = 5.3, 95% CI, 1.5-11) and solvents or chemicals (OR = 3.8, 95% CI 1.5-11) were found. The limited extent of these associations favours a multifactorial aetiology for MND. No relationship to social class, poliovirus infection or to factors which might increase the risk of enteroviral infection in childhood (home space and domestic amenities) was found. Chapter 6 A comprehensive review of previous prognostic studies in MND is presented. An actuarial analysis of the survival of the cohort of 229 incident patients (57 seen in person) in Scotland in 1989-90, with complete follow up for a mean of two years from diagnosis, is calculated on the basis of the SMNDR clinical classification system. The overall 50% survival from diagnosis was 1.2 years (95% CI, 1.0-1.4) and from symptom onset, 2.5 years (95% CI, 2.2-3.0 years). There were significant differences in survival with a poorer prognosis for: progressive bulbar palsy (PBP), female sex and age > 65 years. The presence of PBP and old age were the strongest predictors of outcome, the difference in survival between the sexes was due to the higher frequency of PBP in females. The overall five year survival from symptom onset was 27.7% (95% CI, 19.9-36.0%) but for patients with PBP as the presenting feature was only 3.5% (95% CI, 0.0-15%). These results suggest that, in well defined cohorts, survival can be predicted with some confidence and are useful for the planning of treatment trials. Chapter 7 In this concluding chapter I consider the work contained in this thesis.

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  • EGF and PDGF receptors in endometrial cancer

    Davis, Gregory Keith (1993)

    Doctoral thesis
    The University of Auckland Library

    Despite its relatively good long term survival compared to other cancers in the female, endometrial carcinoma still kills 20% of those women who develop the disease worldwide. Abnormalities in growth factor receptors have been shown to be important in both the prognosis and probably the malignant transformation of the two other oestrogen-dependent cancers, breast and ovary, which suggests that similar defects may occur in endometrial cancer. In this thesis, two of these growth factor receptors, those for the epidermal and platelet-derived growth factors, are studied in endometrial cancer at the levels of the gene and expression of the proteins on the cell surface, in an attempt to detect abnormalities which might be implicated in carcinogenesis. No amplification or rearrangement of the EGFR gene was detected on 13 tumour samples initially, or of the EGF, PDGF α- and β-subunit receptor genes subsequently on a mixture of tumour samples and cell from endometrial cancer cell lines. The size of the EGF and PDGF receptor proteins and the activation of their tyrosine kinase domains was assessed in an oestrogen responsive (Ishikawa) and an oestrogen independent (HEC-1-A) endometrial cancer cell line. Functioning receptors for EGF were demonstrated in both cell lines but no PDGF receptors were detected. EGF-binding studies were carried out and appropriate affinity constants and receptor numbers obtained in both cell lines. The growth of Ishikawa and HEC-1-A cells in culture was studied but because of the rapid growth of both lines in the absence of serum no meaningful mitogenic effects were shown by any growth factor or steroid. Phorbol ester and TGF-β inhibited the growth of HEC-1-A and Ishikawa cells, respectively. Of particular interest was that, despite the reported sensitivity of Ishikawa cells to oestrogen, no consistent stimulation was observed. The growth of both cell lines in the absence of serum suggested that the cells might be secreting growth factors and conditioned medium was obtained from long term, large scale cultures. The medium was concentrated and passed through a size exclusion column and the fractions assayed for DNA synthesis and competition for EGF-binding to Swiss 3T3 cells. No consistent effect on either of these assays was shown and no further investigation was undertaken.

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  • Fetal origins hypothesis in twin children : a metabolic evaluation

    Jefferies, Craig Alan (2007)

    Doctoral thesis
    The University of Auckland Library

    Whole document restricted, but available by request, use the feedback form to request access. This thesis explores whether low birth weight affects glucose homeostasis and other aspects of the metabolic syndrome in twin children. The key parameter studied is insulin resistance, and whether insulin resistance is also associated with abnormalities in blood pressure or other aspects of the metabolic syndrome. This thesis is a comparison of twins to singletons, rather than being a study of these traits within twin pairs. The fetal origins hypothesis suggests that low birth weight ultimately is associated with adult onset diseases namely coronary heart disease, glucose intolerance and hypertension. All twins to a degree are born prematurely and with low birth weight. It is unclear whether their metabolism in later life reflects this, or alternatively reflects their uniqueness as twins irrespective of birth weight. This thesis reviews how adaptation for their unique fetal life has affected in particular, glucose homeostasis in twins. Insulin resistance has been consistently identified prior to the onset of both type 2 diabetes mellitus and hypertension and is also the primary metabolic abnormality persisting from programming of the undernourished fetus. Both small-for-gestational-age and prematurely born infants are insulin resistant when examined in mid-childhood. It has been postulated that this represents an attempt of the fetus to salvage itself from a state of inadequate nutrition. Twins when examined in this thesis are also shown to be insulin resistant, or to have a reduction in insulin sensitivity. This insulin resistance was independent of low birth weight and prematurity, and reflected a unique twin effect. Examing blood pressure precisely revealed that twins had increased night-time blood pressure, a feature also seen in a variety of pre-hypertensive states. However, there was no association between low birth weight and any 24 hour blood pressure monitoring parameter in twins. Twins also had elevated leptin levels but reduced TNF-alpha levels in twins irrespective of birth weight or prematurity. Twins have unique metabolic profiles which are not correlated with low birth weight, and twins should be considered an exception to the fetal origins hypothesis.

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  • Doppler studies in small for gestational age pregnancies and the influence of perinatal variables on postnatal outcomes

    McCowan, Lesley Margaret Elizabeth (1999)

    Doctoral thesis
    The University of Auckland Library

    Background, hypotheses and aims Poor fetal growth is associated with increased perinatal morbidity and mortality. Recently the topic of poor fetal growth has generated considerable research interest, as numerous epidemiological studies have demonstrated that small size at birth is also associated with increased risks of adult cardiovascular diseases and non-insulin dependent diabetes Antenatal treatment aimed at improving fetal growth might therefore reduce perinatal morbidity, as well as later complications of being born small for gestational age (SGA). SGA fetuses with abnormal umbilical artery Doppler studies have placental vascular pathology. Low dose aspirin, which inhibits the production of the powerful vasoconstrictor thromboxane, might therefore increase placental blood flow and fetal growth. The hypothesis in the first antenatal study was that treatment of SGA pregnancies, with abnormal umbilical artery Doppler studies, with aspirin (100 mg) for ≥14 days, would increase fetal weight. As perinatal morbidity and mortality are increased in SGA pregnancies most obstetricians advocate a programme of regular fetal surveillance. Outpatient management with twice weekly fetal surveillance has been usual practice in our hospital in uncomplicated SGA pregnancies. These frequent checks may be unnecessary when umbilical artery Doppler studies are normal as the risk of serious perinatal morbidity is low. More conservative management in SGA pregnancies with normal umbilical artery Doppler studies has been suggested by several authors but has only been evaluated in one previous trial, where hospitalisation was usual practice. In the second antenatal study we therefore wished to test the hypothesis that the frequency of fetal surveillance could be reduced from twice weekly to fortnightly, in SGA pregnancies with normal umbilical artery Doppler studies, without increasing maternal or perinatal morbidity. Abnormal umbilical artery Doppler studies have been shown in a number of reports to be associated with increased perinatal mortality and morbidity, in SGA pregnancies. Previous investigators have not considered the potential confounding effects of both gestational age at delivery and birthweight in relation to umbilical artery Doppler status. SGA babies with normal umbilical artery Doppler studies, have a low risk of complications and have been called ‘small normal babies’ although there is little data to support this claim. In the third antenatal study the following hypotheses were tested: that abnormal umbilical artery Doppler studies would predict newborn morbidity in SGA babies, independent of birthweight and gestational age; that compared with SGA babies with abnormal umbilical artery Doppler studies, SGA babies with normal umbilical artery Doppler studies would have low rates of newborn morbidity and malnutrition; and that their mothers would be smaller, have different ethnic distribution, and have lower rates of vascular problems in pregnancy than mothers of SGA babies with abnormal umbilical artery Doppler studies. After birth approximately 20% of SGA babies fail to show catchup growth and remain short at two years of age. Persisting short stature has been associated with later psychological difficulties, abnormal neurodevelopmental testing in childhood, poor school performance and hypertension in childhood and adult life. Most catchup growth occurs in the first six months after birth and most children who are small at six months will not show further catchup growth. Early identification of children who will remain small may enable interventions aimed at improving later outcomes. There are no previous reports of the influence of perinatal variables on size at six months. In the first postnatal study in this thesis we therefore chose to investigate the perinatal factors associated with small size at six months of age. We tested the hypotheses that children who were small at six months would: have been diagnosed SGA earlier in pregnancy; be more likely to have abnormal umbilical artery Doppler studies; have smaller body proportions at birth; and be more likely to have normal ponderal indices at birth. Previous studies, mostly of children born in the 1960s and 1970s, have reported more abnormal neurodevelopmental test results in children who were SGA at birth compared with appropriate weight for gestational age children. There are very few published studies of neurodevelopmental outcome in SGA children born in the 1990s, who have had the advantage of recent advances in antenatal and especially newborn care. The aims of the second postnatal study were therefore to: assess neurodevelopmental outcome in a cohort of SGA children at 18 months and compare results to a reference population; determine whether one or more of the following perinatal variables might be predictive of abnormal neurodevelopmental test results: early recognition of SGA antenatally, abnormal antenatal Doppler results, lack of participation in the antenatal studies in SGA pregnancies, gestation at delivery, head size at birth, head growth from birth to six months, and ponderal index at birth.

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  • Synthetic studies towards polyketide derived biologically active natural products

    Heapy, Amanda (2010)

    Doctoral thesis
    The University of Auckland Library

    The first part of this thesis describes the successful synthesis of the FG ring fragment 178 of the structurally complex marine toxins, the pectenotoxins. The synthesis hinges on functional group manipulations of the advanced olefin-(Z) 179 to install the tetrahydrofuran and tetrahydropyran ring systems. Olefin-(Z) 179 is itself obtained by the cis selective Wittig olefination of aldehyde 180 and the phosphorus ylide derived from phosphonium salt 181. Key stereocentres of these two fragments are installed using a Katsuki-Sharpless asymmetric epoxidation and a Sharpless asymmetric dihydroxylation reaction, respectively. The second part of this research presents synthetic attempts to access the fungal metabolites cephalosporolides E and F (290). These compounds contain the small but interesting β,γ-fused-[4.4]-spiroacetal-γ-lactone moiety which is a functional group found in seven known natural products, and has until recently eluded the synthetic chemist. A Fukuyama coupling reaction was initially proposed to prepare advanced precursor ketone 474 but proved to be unsuccessful in our hands. A variant of the original Fukuyama reaction was successfully employed to obtain the same advanced ketone 474 but low yielding reactions combined with the delicate nature of this structure posed an insurmountable bottleneck in the planned synthetic strategy. Based on results of the research presented herein, the synthetic strategy towards this family of natural products was revised.

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  • Electroencephalographic effects of general anaesthetics : a suite of clinical studies and theoretical models

    Sleigh, James Wallace (2000)

    Doctoral thesis
    The University of Auckland Library

    The primary object of this thesis was to investigate aspects of empirically-measured, anaesthesia-induced electroencephalographic (EEG) changes that could be explained by network models of cortical interactions. The thesis consists of a collection of various theoretical and clinical papers in three sections: (a) A background section summarizing previous relevant published works on the molecular actions of anaesthetic agents, and the origin and problems with the acquisition of the EEG. (b) A second section dealing with the development of various theoretical / computer models of general anaesthetic action. (c) A third section of various clinical and EEG studies of anaesthesia and sleep. These were done to confirm and clarify some of the theoretical results from the models. However there are many different ways of numerically capturing the information contained within the EEG. Because this problem needed to be overcome before the primary aim of the thesis could be accurately handled; the clinical studies tended to be diverted into this secondary "signal-acquisition" aspect of the EEG analysis in anaesthesia and sleep. Because the thesis has a constellation of different interlocking threads of investigation, I have summarized the various themes in the following table. (A) Background Section The relevant conclusions from the background section were: 1) The transition from aesthesia to anaesthesia involved the whole animal, and thus may not be entirely measurable by the EEG. In contrast the transitions from consciousness to coma - and even more specifically - from mnesis to amnesis were predominantly observable by changes in the activity of the cortex and in the resultant EEG signal. 2) The EEG signal arose largely from the summation of coherent post-synaptic potentials in the cortical pyramidal cells. These were, in turn, mainly controlled by cortical layer-l modulation - which was subject to ascending neuromodulatory systems. 3) The main artifacts in the EEG signal were eye-movements, blinks, and frontalis EMG. 4) The Bispectral index (BIS) consisted of three subcomponents. The first two (BetaRatio and SynchFastSlow) probably reflected the loss of high-frequency activity that is associated with the transition from consciousness to unconsciousness. 5) The state of the midbrain reticular formation projecting via the non-specific thalamocortical connections can profoundly alter the oscillatory state of the cortex and thence the EEG. Direct or indirect actions of general anaesthetic agents on these structures may be a major cause of the observed EEG changes. These changes are qualitatively similar to the changes observed during natural sleep. 6) Although there was variation between different agents, the most consistent action of commonly-used general anaesthetic agents was to prolong the fast inhibitory postsynaptic potential> 50% by GABAergic potentiation. This action was consonant with the observed EEG effects of anaesthesia - which are (1) an increase in EEG spectral power and frequency followed by, (2) a decrease in dominant frequency and overall power with increasing concentrations: the so-called "biphasic response" There were also a number of more specific features: namely loss of alpha band activity, an initial increase in relative beta activity, followed by a shift to lower frequencies, spindles - and in deep anaesthesia - burst suppression patterns. Other contributions to anaesthetic action may include: (1) inhibition of NMDA receptor function, (2) reduction of nicotinic acetylcholine modulation, and (3) a direct hyperpolarizing action by opening potassium channels. Anaesthetic agents disrupted cortical function at lower doses than those required for inhibition of brain stem function. (B) Theoretical Models The fact that the cerebral cortex consisted of, effectively, a two-dimensional interconnecting neural network was of overriding importance. All the theoretical models were constrained by this topological fact, and showed a remarkable degree of similarity. Regardless of whether the model was continuous (appendix 2) or discrete (cellular automata), some robust and consistent features emerged: 1) Some form of abrupt decrease in information flow within the network occurred when the interaction between the network elements was interrupted greater than certain critical threshold amount - the order/disorder phase transition. 2) This critical point was manifest as (i) a large change in the simulated mean soma potential (the order parameter), (ii) divergence of the spectral power of the simulated pseudoEEG signal, and (iii) decrease in frequency content (in the cellular automaton models). Unfortunately the order parameter for the EEG is probably unmeasurable in clinical practice. The first derivative is measurable, but not completely reliable as a proxy order parameter. 3) All models required some form of noisy external (subcortical) input to drive them. Variations in this input could explain some of the anomalies observed in the clinical section of the thesis. (C) Clinical Papers The clinical papers were a series of papers recording the clinical data, which then influenced the development of the theoretical models. The single most popular clinical measure of anaesthetic depth in present practice is the Bispectral Index (BIS). Many of these studies explore the strengths and weaknesses of this index in various clinical situations. The main disadvantage of the BIS was that crucial aspects of its formulation are not in the public domain for commercial reasons. We attempted to separate out the changes in the various subcomponents of the BIS in patients under general anaesthesia, and natural sleep. 1) In the first paper we described how the EEG changed during induction and recovery from general anaesthesia with propofol and isoflurane. We compared EEG vs heart rate variability changes as monitors of anaesthetic depth. This study served to evaluate a clinically accepted measure of anaesthetic depth, as well as gaining practical EEG experience in collecting experimental data, both using the ASPECT EEG monitor, and in devising the best clinical methods of quantifying levels of consciousness. The main results were that the BIS was relatively reliable in steady-state conditions, and better than the raw 95% spectral edge frequency, and the approximate entropy of the EEG. 2) Auditory recall and response-to-command during recovery from propofol anaesthesia. In this paper we were able to collect data in a very controlled situation, somewhat different from that pertaining to clinical practice. From this we were able to identify separate components of consciousness and mnesis and how they correlated with EEG changes. We were also able to compare frontal and parietal EEG data. We established that there is a clear divergence of spectral power around the time of loss-of-consciousness when the propofol was administered as a slow infusion. This is good evidence supporting the basis of the theoretical models. This experiment also established that it is possible for a patient to be conscious, not paralyzed, but not responding to verbal command. 3) Electroencephalographic measures of depth of anaesthesia: the importance of the gamma band and the electromyogram signal. This study was concerned with different technical aspects of EEG signal acquisition and processing. It suggested that usually the EMG is not a significant problem, and that the gamma (40-60Hz) frequency band is important in distinguishing the awake from the anaesthetized state. 4) The Bispectral Index: A Measure of Depth of Sleep? Because the EEG changes of general anaesthesia are very similar to those of sleep, this study was a simple observational study collecting some information about changes in the BIS with natural sleep. 5) The Bispectral Index and Sleep Stage: A Polysomnographic study. In this study we formally compared the BIS with a full polysomnogramnographic sleep staging. It confirmed the results of the previous study, and demonstrated that the subcomponents of the BIS (the BetaRatio and the SynchFastSlow) changed in a manner very similar to those observed under general anaesthetic. Conclusions The observed changes in the EEG on induction of anaesthesia can be explained by changes in relatively simple theoretical network models. These changes can be reliably reduced to univariate Parameters

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  • Lipiodol fertility enhancement in unexplained and endometriosis-related infertility

    Johnson, Neil Philip (2007)

    Doctoral thesis
    The University of Auckland Library

    Objectives This thesis had the following objectives: 1) To assess the existing evidence base for the effectiveness of tubal flushing as a treatment for infertility (Section II, Chapters 4 and 5). 2) To assess current practice and prior beliefs amongst Australasian fertility specialists concerning the role of tubal flushing as a treatment for infertility (Section III, Chapter 6). 3) To investigate the possible mechanism of the fertility enhancing effect of the oil soluble contrast medium lipiodol, and specifically whether there is an effect on the endometrium (Section IV, Chapter 7). 4) To generate definitive evidence from a randomised controlled trial for the effectiveness of lipiodol flushing as a treatment for infertility (Section V, Chapters 8 and 9). 5) To evaluate the adoption of lipiodol flushing as an innovative treatment into clinical practice (Section VI, Chapter 10). Methods The work undertaken in this thesis was based on prospective study protocols using the following research methodologies: Systematic reviews and meta-analyses of treatment efficacy to meet objective 1. Two types of structured survey questionnaires with a Bayesian analysis to meet objective 2. A randomised animal study involving 60 Swiss white mice, combined with genital flushing procedures under anaesthesia, some of which involved microsurgical techniques, followed by genital tissue harvesting, tissue preparation and immunohistochemistry studies to meet objective 3. An open, parallel group, single centre, randomised controlled trial involving 158 women with unexplained and endometriosis-related infertility to meet objective 4. A survival analysis of women in the lipiodol flushing randomised trial to meet objectives 4 and 5. A prospective observational study of the first 100 women to undergo lipiodol flushing in clinical practice to meet objective 5. A clinical hysterosalpingogram procedure to meet objective 4 and 5. Results 1) Eight randomised controlled trials involving 1,971 women were identified and included in the systematic review. Tubal flushing with oil soluble contrast media versus no intervention was associated with a significant increase in the odds of pregnancy (Peto odds ratio [OR] 3.57, 95% confidence interval [CI] 1.76 to 7.23) but there were no data for live birth. There were no data from RCTs to assess tubal flushing with water-soluble media versus no intervention. Tubal flushing with oil soluble contrast media was associated with a significant increase in the odds of live birth versus tubal flushing with water soluble contrast media (OR 1.49, 95% CI 1.05 to 2.11) but the odds of pregnancy showed no significant difference (OR 1.24, 95% CI 0.97 to 1.57) and there was evidence of statistical heterogeneity for these two outcomes. The addition of oil soluble contrast media to flushing with water soluble contrast media (water plus oil soluble contrast media versus water soluble contrast media alone) showed no significant difference in the odds of live birth (OR 1.06, 95% CI 0.64 to 1.77) or pregnancy (OR 1.16, 95% CI 0.78 to 1.70). 2) Nineteen Australasian fertility specialists returned survey questionnaires. Eighteen of the 19 specialists believed that lipiodol flushing was more likely to be beneficial than harmful. The most widely held prior belief, reflected in both textual and numerical responses, was that lipiodol was likely to produce a small beneficial response. The credible limits of this belief were compatible with a reasonable fertility benefit, as more than 50% believed that a 1.5-fold increase in pregnancy rate was plausible. The two surveys found that a 1.2-fold or 1.4-fold increase in pregnancy rate was the median expected level of benefit at which clinicians would have been inclined to recommend lipiodol flushing to their patients (combined range 1.1 to 2.3-fold). Individual and collective equipoise was justification to proceed with a definitive randomised controlled trial. 3) The mean number of cluster determinant (CD) 205+ uterine dendritic cells decreased significantly in mice following lipiodol treatment compared to sham treated and saline treated mice, particularly in endometrial and subendometrial tissues. The mean number of CD1+ uterine dendritic cells increased significantly following lipiodol treatment compared to shamtreatment. No significant differences were found in the mean number of total leukocytes or macrophages in the murine uterus between the three treatment groups. 4) Six month follow up of the randomised trial of 158 women showed that lipiodol flushing resulted in a significant increase in pregnancy (48.0% versus 10.8%, RR 4.44, 95% CI 1.61-12.21) and live birth (40.0% versus 10.8%, RR 3.70,.95% CI 1.30-10.50) rates versus no intervention for women with endometriosis (n=62), although there was no significant difference in pregnancy (33.3% versus 20.8%, RR 1.60, 95% CI 0.81-3.16) or live birth (27.1% versus 14.6%, RR 1.86, 95% CI 0.81-4.25) rates for women with unexplained infertility without confirmed endometriosis (n=96). Survival analysis up to 24 months showed a significant benefit in overall pregnancy rate following lipiodol treatment (hazard ratio 2.0, 95% confidence interval [CI] 1.3 to 3.2) for the combined endometriosis and unexplained infertility populations. Amongst women with endometriosis, the benefit in pregnancy rate seen in the first 6 months following lipiodol (hazard ratio 5.4, 95% CI 2.1 to 14.2) was not present at 6 to 24 months following lipiodol (hazard ratio 0.6, 95% CI 0.2 to 2.1). There was a more consistent effect of lipiodol on fertility throughout the 24 month follow up amongst women with unexplained infertility (hazard ratio 2.0, 95% CI 1.1 to 3.5). 5) Six month follow up in the observational study of 100 women undergoing lipiodol flushing as an innovative treatment in clinical practice showed an overall pregnancy rate 30% and live birth or ongoing pregnancy rate 27% six months after the procedure. For women under 40 years old, a 32% pregnancy rate and 25% live birth or ongoing pregnancy rate was seen in women with unexplained infertility; a 50% pregnancy rate and 47% live birth or ongoing pregnancy rate was seen in women with endometriosis. Of women aged 40 years and older, the pregnancy rate was 13% and the live birth or ongoing pregnancy rate was 13%. The pregnancy rates included those occurring after additional interventions, such as intrauterine insemination and in-vitro fertilisation, accounting for 12 of the 30 pregnancies. There were no treatment complications. Conclusions The conclusions of this thesis are as follows. Lipiodol flushing is a simple, inexpensive, effective fertility treatment, which carries a very low chance of complications and no increased chance of multiple pregnancy. Lipiodol treatment is particularly effective in the short term for women with endometriosis who have normal patent fallopian tubes. The fertility benefit from lipiodol treatment lasts longer for women with pure unexplained infertility than for women with endometriosis. The level of benefit from lipiodol treatment for women with unexplained and endometriosis-related infertility is of sufficient magnitude to convince most fertility specialists surveyed that it is a worthwhile treatment to offer routinely in clinical practice; however complex factors govern the implementation of an innovative fertility treatment. Observational study of the first 100 women to undergo lipiodol treatment in clinical practice has provided further evidence of the efficacy and safety of this approach. Uterine dendritic cell changes following lipiodol flushing in mice suggest that the mechanism of the fertility enhancing effect might be an immunobiologic effect on the endometrium that could improve the receptivity of the endometrium (rather than a mechanical tubal flushing effect), although this hypothesis requires further exploration in women.

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  • Analysis of eye banking and corneal transplantation in New Zealand

    Patel, Hussain Y (2007)

    Doctoral thesis
    The University of Auckland Library

    The series of studies comprising this thesis was developed to answer a number of key inter-related questions in regard to eye banking and corneal transplantation in New Zealand. The source and management of donor tissue procured by the New Zealand National Eye Bank (NZNEB) was analysed. Significant trends were identified with respect to donor demographics, donor procurement source, improved donor tissue processing and storage, decreased biological contamination, and increased utilization of corneal tissue. Current trends and ethnicity differences in indications for penetrating keratoplasty (PKP) were investigated. Keratoconus was identified as the most common indication for PKP in New Zealand, accounting for a significantly higher proportion of PKPs than other published reports. Keratoconus was the most common indication for PKP throughout all ethnicity groups and was particularly common in the Maori and Polynesian populations. Significant trends were identified including an increase in the number of PKPs for regraft and Fuchs’ endothelial dystrophy and a decrease for aphakic or pseudophakic bullous keratopathy and viral keratitis. Survival and visual outcome following PKP in New Zealand was investigated using univariate and multivariate analysis. Several independent risk factors were identified that influenced outcome of PKP. Active inflammation at PKP, pre-existing vascularisation, pre-operative glaucoma, small or large graft size, intra-operative complications, episodes of reversible rejection and a pre-operative diagnosis of regraft, trauma or infection resulted in a significantly decreased survival rate. Advancing recipient age, active inflammation at the time of PKP, pre-existing vascularisation, pre-operative glaucoma, episodes of reversible rejection, bullous keratopathy, trauma and non-infective keratitis were associated with poor visual outcome. Patient characteristics, indications, surgical details, and outcome of paediatric keratoplasty were analysed. Acquired non-traumatic indications accounted for the majority of paediatric keratoplasties in New Zealand. This study highlighted keratoconus as a particularly common indication for paediatric keratoplasty when compared to other countries. Survival and visual outcome was better for acquired compared to congenital indications. The effects of corneal parameters on the measurement of endothelial cell density (ECD) in the normal eye were analysed. Corneal thickness appears to be negatively correlated to ECD in the normal cornea for all age groups. Corneal diameter is correlated to ECD measurement in children but not in adults. Corneal curvature was not significantly correlated to ECD measurement, but this needs further investigation. Confocal microscopy and slit scanning topography were used to analyze endothelial morphology and function in the short and long term following PKP. The results of this study are in concordance with other published reports that have identified an accelerated loss of endothelial cells and more rapid development of abnormal endothelial cells in transplanted corneas compared to normal corneas.

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  • Understanding the notion of interdependence, and the dynamics of willingness to communicate

    Cao, Yiqian (2009)

    Doctoral thesis
    The University of Auckland Library

    The current individual differences research in the field of second language acquisition (SLA) addresses the issue of the situated nature of individual difference (ID) factors. Willingness to communicate (WTC) is a relatively new ID variable in SLA (Dörnyei, 2005) and it is seen as both a facilitating factor of SLA and a non-linguistic outcome of the second language learning process (MacIntyre, 2007). Previous research into WTC primarily focused on its trait disposition as remaining stable across situations. Only a handful of studies have revealed that the construct might be situation-specific rather than fixed. The present study investigated the dynamic and situated nature of second language (L2) learners’ WTC in class. Framed within a sociocognitive perspective on L2 learning which draws together social, environmental and individual factors, this classroom-based multiple case study involved 18 English as an additional language (EAL) learners in New Zealand over an academic year and was implemented in three phases. Data were collected through classroom observations, stimulated-recall interviews, semi-structured interviews and reflective journals. Evidence from self-report and observational data suggests that the classroom WTC construct is best described as a dynamic situational variable rather than a trait disposition. The findings indicate that situational WTC in class results from the interdependence between individual characteristics, classroom environmental conditions and linguistic factors. These three strands of factors interdependently exert either facilitative or inhibitive effects on an individual student’s WTC in class at any point in time. The effect of the combinations of factors differs between individuals and the interrelationship is too complex to be predicted. This study has attempted to describe and measure the WTC construct as situated in L2 classrooms and it serves as a stepping stone for further research on the role of WTC in L2 learning.

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  • Second chances: youth justice co-ordinators’ perspectives on the youth justice family group conference process.

    Slater, Christine Marie (2010)

    Doctoral thesis
    The University of Auckland Library

    In New Zealand’s system of Youth Justice (YJ) the Family Group Conference (FGC) process plays a pivotal role in addressing the offending behaviour of young people under seventeen. Mandated under the Children, Young Persons, and their Families Act 1989 (the Act), the FGC is a formal meeting in which the persons most affected by a young person’s offending, typically the young person, their family, their victim(s) and associated professionals, collectively decide how the young person should be held accountable. The process is managed by a YJ Co-ordinator, appointed by the Department of Child, Youth and Family (the Department). This dissertation presents the findings of an evaluation of the YJ FGC process from the perspectives of YJ Co-ordinators. The study aimed to understand the process and the development of practice, to identify factors constituting best practice and current areas of weakness in the process. It comprised of semi-structured interviews with (n=19) YJ Co-ordinators with at least twelve years’ practitioner experience (Project One) and four focus groups (n=27) of Co-ordinators with a range of practice (Project Two). Three major themes emerged from the thematic analysis of data: a) The Act as Anchor – philosophical underpinnings of the FGC process, b) Working with the Act – best practice and current issues in YJ FGC service provision, and c) The Office – organisational factors. The results indicated the YJ FGC process was effective for the majority of young people, but generally inadequate for recidivist young offenders with complex additional needs. Aspects of best practice included: aligned professional approaches to FGC philosophy and practice, service delivery by trained YJ Co-ordinators and the quality of FGC preparation. Also considered best practice was the inclusion of victims in the process to assist in the development of a strengths-based personalised plan for the young person. With several areas of weakness identified, recommendations for improving the process included: addressing Co-ordinator training and Departmental leadership, reviewing the process for recidivists, improving process information quality, enhancing professional collaboration and addressing Police training in the Act and the FGC. Limitations of the study and directions for future research are discussed.

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