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    Bayesian methods to address multiple comparisons and misclassification bias in studies of occupational and environmental risks of cancer : a thesis by publications presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Public Health, Massey University, Wellington, New Zealand
    (Massey University, 2013) Corbin, Marine
    In this thesis I explore the application of several Bayesian approaches, implemented with standard statistical software, in environmental and occupational epidemiology. These methods are applied to case-control studies of occupational risks for lung and upper aerodigestive tract cancers conducted in New Zealand and Europe. The findings are of interest in themselves, but the focus of the thesis is on the application of Bayesian methods to produce these findings. It is not intended to represent a comprehensive overview of all Bayesian methods, but rather to explore Bayesian methods which are most appropriate for the studies which are presented here. In the first section, I review the underlying theory involved in such analyses. In the second section, I use Bayesian methods to address the problem of multiple comparisons. In occupational case-control studies, we may collect information on hundreds of occupations/exposures for which there is little or no prior evidence. For those occupations/exposures, we get a false positive finding by chance about 5% of the time. This means that if we repeat the study in a new population, these chance associations are likely to exhibit ‘regression to the mean’ and will not show such extreme risks again. Bayesian methods can be used to ‘shrink’ effect estimates based on how strong the regression to the mean is likely to be. In the third section, I use Bayesian methods for assessing and correcting systematic error. Although the methods I use can be applied to several situations (selection bias, misclassification, residual confounding), I apply them to the specific situation of misclassification of the main exposure. In particular, I apply four different methods for such sensitivity analyses: multiple imputation for measurement error (MIME); imputation based on specifying the sensitivity and specificity (SS), Direct Imputation (DI) of the ‘true’ exposure using a regression model for the predictive values and imputation based on a fully Bayesian analysis. I conclude by summarising the strengths, limitations, and areas of future development for the use of these methods. It is anticipated that, in 5-10 years time, such analyses may become standard supplements to ‘traditional’ forms of analysis, i.e. that Bayesian methods may be routinely used, and may form part of the ‘epidemiological toolkit’ for assessing and correcting for both random and systematic error.
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    Morphological effects of pulsed Doppler diagnostic ultrasound on rat adult lung and fetal tissues : a thesis presented in fulfillment of the requirements for the degree of Master of Science in Physiology and Anatomy at Massey University
    (Massey University, 1999) Dulović, Stanica Milan
    This study investigated morphological effects of diagnostic pulsed Doppler ultrasound on adult and fetal rat lungs from 16 to 22 days gestation. A clinical ultrasound machine with two types of focused transducers (3.5 MHz, 5MHz) was used with an adjustment for an experimental animal as small as a rat. Three levels of exposure were represented by a mechanical index (Ml) of 0.5, 0.6 and 1.0. Subpleural multifocal intra-alveolar haemorrhage was found to a significant degree in exposed adult rat lung and less significantly in fetal lung. The threshold for adult lung haemorrhage was considered to be between Ml 0.5 and 0.6. Fetal lungs were microscopically investigated by sectioning through the whole fetal body, which facilitated the discovery of haemorrhage at other sites. The percentage of exposed fetuses with haemorrhage is significant. A threshold for fetal haemorrhage could not be determined because a significant variation due to age within each exposure group affected the results. The oldest 21 and 22 day old fetuses had no lung haemorrhage or significant non-lung haemorrhage. The risk for haemorrhage at all three exposure levels is more than double that of non exposed fetuses. Fetuses with lung in the canalicular stage of development (18-19 day) showed the greatest degree of lung haemorrhage. Following laparotomy of the dam to achieve a precise and uniform exposure, a small number of fetuses within each exposure group was exposed directly. There was no higher degree of haemorrhage in these fetuses than in others indirectly exposed through the dam's abdominal wall. The fetal age dependency of fetal lung haemorrhage found in this study adds complexity to the issue of adult and fetal lung sensitivity to ultrasound and to the question of the pathophysiological role of cavitation in the presence of air. In addition, our result in 21-22day fetuses does not support the hypothesis that fetal haemorrhage is associated with developing bone. The results in this study were achieved using conditions commonly used in echocardiography and obstetrical ultrasound examinations. Therefore, caution is suggested in the medical use of ultrasound.