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Item Statistical inference for population based measures of risk reduction : a thesis presented in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Statistics at Massey University, Palmerston North, New Zealand(Massey University, 2019) Pirikahu, SarahEpidemiologists and public health practitioners often wish to determine the population impact of an intervention to remove or reduce a risk factor. Population attributable type measures, such as the population attributable risk (PAR) and population attributable fraction (PAF), provide a means of assessing this impact in a way that is accessible for a non-statistical audience. To apply these concepts to real-world data, the calculation of estimates and confidence intervals for these measures should take into account the study design and any sources of uncertainty. We provide a Bayesian approach for estimating the PAR and its credible interval, from cross-sectional data resulting in a 2 × 2 table, and assess its Frequentist properties. With the Bayesian approach proving superior this model is then extended by incorporating uncertainty due to the use of an imperfect diagnostic test for exposure. The resulting model is under-identified which causes convergence problems for common MCMC samplers, such as Gibbs and Metropolis- Hastings. An alternative importance sampling method performs much better for these under- identified models and can be used to explore the limiting posterior distribution. However, this comes at the cost of needing to identify an appropriate transparent parameterisation, which can be difficult. We provide an adaptation of the Metropolis-Hastings random walk sampler which, in comparison to other MCMC samplers, more efficiently explores the posterior ridge of an under-identified model for large sample sizes. Often data used to estimate these population attributable measures may include multiple risk factors in addition to the one being considered for removal. Uncertainty regarding the distribution of these risk factors in the population affects the inference for PAR and PAF. To allow for this uncertainty we propose a methodology where the uncertainty in the joint distribution of the response and the covariate is accommodated.Item An investigation into the link between vitamin D status, erectile dysfunction and cardiovascular risk factors in ageing men in New Zealand : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Nutritional Science at Massey University, Palmerston North, New Zealand(Massey University, 2016) Quilter, Merrin LouiseBackground Cardiovascular disease (CVD) is the leading cause of death worldwide, particularly amongst ageing males. Prevention and/or early identification and effective intervention are essential in the fight against CVD. Erectile Dysfunction (ED) is a prevalent and multi-factorial condition that is now accepted to be an early marker of subclinical CVD: the common denominator is endothelial dysfunction. Both the enzymatic capability for bioactivation of Vitamin D and the vitamin D receptor (VDR) are expressed in endothelial cells and vitamin D may play a role in endothelial function. Vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) concentrations ˂50 nmol/L) is a worldwide pandemic and serum 25(OH)D levels ˂75 nmol/L may result in metabolic and vascular deterioration leading to endothelial dysfunction, ED and CVD. Assessment of erectile function can be used to identify otherwise asymptomatic men at high risk of developing clinical CVD, at a time when effective intervention may prevent, delay or reverse its progression. Vitamin D status may be associated with ED and CVD risk and could help improve erectile function and vascular health. Objectives The aim of this research was to investigate the postulated link between vitamin D status, ED, and CVD risk factors. The objectives were (1) to assess the prevalence of ED (using the 5-item International Index of Erectile Function (IIEF-5)) and its associated sociodemographic, lifestyle, and medical correlates in New Zealand (NZ) men aged 40-70 years; (2) to investigate the relationship between vitamin D status (serum 25(OH)D concentration), ED and other CVD risk factors in men aged 40-70 years living in the Manawatu region of NZ; and (3) to examine the impact of common VDR gene (VDR) polymorphisms on this relationship. Method Two thousand men aged 40-70 years were randomly selected from the NZ Electoral Roll and sent an anonymous postal survey designed to assess the prevalence of ED and its sociodemographic, lifestyle, and medical risk factors. Six hundred men aged 40-70 years living in the Manawatu region were randomly selected from the NZ Electoral Roll and invited to participate in an observational study designed to provide a comprehensive health profile of self-reported healthy men and investigate the relationship between vitamin D status, ED, and a range of CVD risk factors. Eligible participants (n=100) completed a comprehensive health assessment including a medical history, anthropometric and cardiovascular assessment, fasting blood sample, computer-based questionnaire, a submaximal fitness test and a handgrip iv strength test. Blood samples were assessed for four common VDR polymorphisms (rs11568820 (Cdx2), rs10735810 (FokI), rs1544410 (BsmI) and rs731236 (TaqI)) using polymerase chain reaction-high resolution amplicon melt (PCR-HRM) analysis. Results The survey showed 38.4% of respondents presented with ED (IIEF-5 ≤21). Older age, non-European ethnicity and current smoking were significant independent predictors of an increased risk of ED, while a high household income and regular vigorous physical activity (PA) were deemed protective. The observational study showed 30 men presented with ED and a further 37 men had <75 nmol/L 25(OH)D. There was a weak positive correlation between IIEF-5 scores and 25(OH)D levels (rs=0.238, p=0.017). Men with <75 nmol/L had lower IIEF-5 scores compared to men with ≥75 nmol/L 25(OH)D (22(7) vs. 24(3), p=0.001). Men with ED had lower 25(OH)D levels compared to men without ED (74.5(34) vs. 84.5(24), p=0.062). Every 1 nmol/L of 25(OH)D predicted a 2% decrease in the age-adjusted risk of ED (age-adjusted OR=0.98 [0.96-1.00], p=0.046). The PCR-HRM analysis showed that the Cdx2, FokI and BsmI polymorphisms were all significantly associated with an adverse cardiovascular risk profile. The Cdx2 G allele was associated with lower IIEF-5 scores compared to the A allele (23(4) vs. 24(2), p=0.008) and the GA and GG genotypes were predictors of an increased age-adjusted risk of ED (age-adjusted OR=18.78 [1.98-178.60], p=0.011 and 8.53 [1.00-72.73], p=0.050 respectively). However, Cdx2 was not found to modify the age-adjusted association between 25(OH)D levels and ED (multi-adjusted OR=0.97 [0.95-1.00], p=0.032). Conclusions These results suggest that over a third of NZ men aged 40-70 years suffer from ED and it is associated with sociodemographic, lifestyle and medical factors similar to CVD. Low serum 25(OH)D is associated with the presence and severity of ED in a self-reported healthy population. Common VDR polymorphisms are also associated with ED; however, they do not modify the association between serum 25(OH)D and ED. A randomised placebo-controlled human intervention trial is warranted to investigate whether improving vitamin D status in men with vitamin D deficiency and ED ameliorates symptoms and reduces the risk of CVD.Item Development of a method for optimal detection of emerging disease incursions : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Philosophy at Massey University, Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North, New Zealand(Massey University, 2016) Wang, ShiyongEmerging and re-emerging infectious diseases (ERID) are capable of generating sizable economic loss, and causing loss of life and social instability. To prevent and mitigate the negative impacts of ERID, it is imperative to have a sensitive surveillance system for early disease detection. Furthermore, from the economic perspective, resources are always scarce and have opportunity cost, so investment in surveillance programs has to demonstrate that it can maximize the utility of available resources. The thesis was focused on development and application of a software toolbox, Human and Animal Disease Response Program (HandiResponse), designed for (i) visualizing the disease risk landscape and representing spatial variation in the expected occurrence of a zoonotic disease both quantitatively and visually; (ii) evaluating economic benefit and costs of a single surveillance activity or a multi-component portfolio; (iii) identifying optimal use of resources for surveillance. It comprises four modules: (i) risk map development – HandiMap; (ii) surveillance portfolio development – HandiSurv; (iii) economic impact assessment – HandiEcon and (iv) surveillance optimization – OptiSurv. The modules developed were tested on a number of data sets from various countries. The experience demonstrated that using satellite-derived data in combination with national statistical data to produce a disease risk map improved spatial prediction of avian influenza H5N1 outbreaks in southern Vietnam. Development of a risk map from satellite data for Crimean Congo Haemorrhagic Fever for Mongolia guided a field surveillance program which provided the first evidence that this disease is present in both animals and people in Mongolia. Finally an invented disease affecting pigs and people was used to investigate the likely consequences of an incursion of such a novel disease into Australia, involving both domestic and feral pigs and transferring to people. Risk-based and classical disease surveillance options were then tested for disease detection, and modelling work confirmed that a portfolio consisting of different options was the most technically and economically appropriate. HandiResponse is a practical tool that could promote the implementation of risk-based surveillance approaches, and improve both technical and economic efficiency of surveillance programs for infectious diseases, particularly those affecting both people and animals.Item Investigation of hygiene aspects of pig processing using the HACCP concept : a dissertation presented in partial fulfilment of the requirements for the degree of Master of Veterinary Studies in Veterinary Public Health at Massey University(Massey University, 1999) Vu, Quynh NContamination of fresh meat by pathogenic and spoilage microorganisms can occur at any stage of the slaughter process. Pathogens which are frequently found in fresh meat and which pose a public health problem include Salmonella spp. Campylobacter spp. and Yersinia spp. Contamination with spoilage bacteria affects the storage stability and shelf life of meats. Factors that contribute to meat spoilage include physical damage, biochemical changes in the meat tissues and the activity of microorganisms, of which bacteria are undoubtedly the most important. Fresh meats present a rich medium for the support of microbial growth and will ultimately be rendered unacceptable to consumers as a consequence of spoilage due to such growth. The source of spoilage bacteria can be the slaughter animals themselves, the environment, water and personnel working in the processing plants. This study was conducted to determine the effect of some processing operations on the level of contamination of the pig carcass with aerobic bacteria and to establish microbial quality control points based on the Hazards Analysis Critical Control Point (HACCP) principles. As a component of the HACCP system and a step in the setting up of an HACCP plan for microbial quality control of fresh carcass meat, this study aims at identifying hazards at various stages of processing, evaluating preventive measures and establishing critical control points. Where appropriate, corrective measures to ensure that bacterial contamination is within an acceptable level are recommended. The study was carried out at a processing plant in the North Island of New Zealand during the period April to July 1998. Based on observations at the plant, a flow chart of pig processing was drawn up. A number of processing stages were selected as points where potential risks of bacterial contamination were most likely to occur. These points initially included dehairing, polishing and scraping, evisceration, and inspection. Eight visits to the abattoir were made and a total of 32 paired swab samples from carcasses at each process stage were collected. With four process stages selected for sampling, the total number of samples was 128. In addition, 12 scalding tank water samples were collected for analysis. All samples were processed in the Microbiology Laboratory at Massey University. The aerobic plate count (APC) technique employing incubation at 30°C for 3 days was used for enumeration of aerobic bacteria. A matrix table was designed for entering APC data after each count. The mean of colony forming units per square cm (CFU/cm2) for pig carcass surfaces and CFU/ml for scalding water were calculated and log10 transformation was performed. The highest mean APC was found after the carcasses had passed the dehairing machine (5.1 log10/cm2, ST.D. = 0.57) and the lowest number before the dehairing step (4.31 log10/cm2, ST.D. = 0.61). A rapid increase in APC at the dehairing stage indicated a heavy recontamination of the pig carcass with bacteria from the equipment and from detritus accumulated during the operation. After the operation, the count gradually decreased to 4.4 log10/cm2, ST.D. = 0.38 at the post-evisceration point but then slightly rose again to 4.5 log10/cm2, ST.D. = 0.4 at the post-inspection step. The increase in the APC at the dehairing stage by 0.8 log10/cm2 (p = 0.0002, n = 16) is significant. There was little change in the APC at the polishing and scraping and evisceration stages. There was an insignificant difference of 0.2 log10/cm2 in the APC between samples taken at the start and at the end of the shift. The scalding water temperature fluctuated between 60°C and 67.5 °C (mean = 63.2, n = 12). Bacterial contamination of the scalding water remained almost unchanged with time (2.55 log10/ml at the beginning and 2.62 log10/ml at the end of the shift). An expected inverse correlation between scalding water counts and water temperature could not be verified. Although this study is confined to the microbiological assessment of only a few operational stages that can contribute to the storage quality of fresh pork, the results showed that recontamination of the pig carcass at the dehairing stage is serious and may pose potential safety and quality hazards. Control of bacterial contamination at this step is likely to have a beneficial effect on the microbial quality and safety of the final products. A quality Critical Control Point should be established at the dehairing step which can be considered as a safety CCP as well. However, some technological modification at this step such as installation of hot water showers to make the operation "specifically designed", may be needed to meet the criteria for establishing a CCP. At the polishing and scraping step the results of the study indicated a slight decline in bacterial numbers, provided that brushing and washing of the carcasses was done properly. Any deviation from the normal procedure e.g. inadequate water supply to the brush and scraping table, reduced frequency of hand and knife washing, or increased frequency of touching the carcass by the worker's hands, is likely to result in an increased level of bacterial contamination. Monitoring measures and corrective actions at this stage could be crucial for maintaining an effective CCP. At the evisceration step, preventive measures such as plugging or tying the anus should be considered. This step could be an important CCP for both quality and safety. Further investigations are required to assess the effect of meat inspection procedures on the spread of bacteria from multiple incisions of lymph nodes, internal organs and tonsils. If this step were to be considered a CCP, it would mainly have safety implications.
