1,854 results for Thesis, 2011

  • Molecular and bioinformatic analysis of the perA locus in Epichloë : this thesis is presented as a partial fulfilment of the requirements for the degree of Master of Science (M.Sc.) in Genetics at Massey University, Palmerston North, New Zealand

    Berry, Daniel (2011)

    Masters thesis
    Massey University

    Fungal endophytes of the Epichloë genus form largely mutualistic symbioses with coolseason grasses, systemically colonising the intercellular spaces of the host in a strictly regulated fashion. The endophyte receives protection and sustenance from the host, and in return provides benefits such as increased growth, drought resistance and protection against herbivores. Protection against herbivory is mediated through the production of bio-protective fungal secondary metabolites (SM). Examples of these SMs include lolitrem B, the causative agent of ‘ryegrass staggers’ in stock, and the insect feeding deterrent peramine. The genes responsible for the production of each of these SMs are usually found clustered together in the genome, and are often closely associated with a range of transposon relics. SM gene expression occurs only when the endophyte is growing in planta, indicating the presence of plant-fungal signalling. This study investigated the locus structure and organisation of the gene perA that encodes the non-ribosomal peptide synthetase PerA, which is both essential and sufficient for production of peramine. It was found that perA and its flanking intergenic sequences exhibit considerable transposon-mediated variability across Epichloë, and that this transposon activity is likely responsible for the taxonomically discontinuous production of peramine both within and across Epichloë spp. The major facilitator superfamily transporter gene EF102 is divergently transcribed from and co-regulated with perA (EF103). Transcriptome data were used to identify transcription start sites for both genes. Comparative analysis of the intergenic sequence separating EF102/perA from 10 Epichloë isolates covering six different species refined the perA translation start site, and identified conserved regions in the promoters of both genes proposed to be important for regulation. A motif search identified a conserved DNA motif present multiple times in the promoters of both genes. Deletion analysis of EF102 revealed the gene probably does not encode a peramine transporter, as was hypothesised; however the four independent ΔEF102 mutants exhibited a reduction in peramine production relative to wild type, resulting in an alternative hypothesis that EF102 encodes a transporter for a PerA substrate precursor molecule such as glutamate.

    View record details
  • Parent and teacher knowledge of head injuries : a thesis presented in partial fulfilment of the requirements for the degree of Master of Arts in Psychology at Massey University

    McKay, Erin Anne (2011)

    Masters thesis
    Massey University

    This study examined parents and teachers knowledge of aspects of head injury (HI). Part one examined the various sources of information and education parents and teachers have access to that could impact on their knowledge of HI. Part two surveyed 64 parents and 64 teachers of young children (s knowledge of HI. A more complete form of the survey could be used to get a well rounded picture of the current knowledge base of HI.

    View record details
  • 'An education system characterised by equity' : a critical evaluation of educational change in Samoa, 1995-2005 : a thesis presented in partial fulfilment of the requirements for the degree of Doctor of Education at Massey University, Palmerston North, New Zealand

    Male, Alan G R (2011)

    Doctoral thesis
    Massey University

    The problem investigated in this thesis arose from my professional practice as a consultant with regard to educational reforms in a number of countries, including Samoa. This created an initial interest in why different policy options were chosen by different countries in response to similar problems. Observation of the implementation of reforms in various contexts also created questions as to why the implementation of reforms often seemed to lead to new formulations of the original arrangements, resulting in development but little change. A prior review of evaluations of educational reform programmes showed that many educational evaluations are confined to matters of technical advice inputs, resource management and the achievement of milestones. This study however, considers other factors relevant to the successful achievement of an educational reform programme situated within a particular social, political and historical context. In particular, this thesis reports on a critical evaluation of the development, between the mid-1980s and 1994, of a policy aimed at producing an education system “characterised by equity” (Department of Education, 1995) in Samoa and then on the results of the implementation of that policy between 1995-2005. The study focused first on the differences in the performance of student groups based in the national Year 8 secondary school selection examination and in their subsequent access to secondary schooling and to the achievement outcomes in Year 12 over the period between 1994 and 2008. Information was gathered through analysis of national examination results databases. Additional information was gathered through interviews and questionnaires from senior educational system managers and from the principals of a sample of four secondary schools. Questionnaires, aimed at gathering socio-economic data, were administered to 2000 students and their families from Years 9, 11, 12 and 13 at the sample schools. The evidence showed little change in the patterns of achievement between advantaged and disadvantaged groups. The system had expanded but the patterns of inequity remained unchanged. The reasons for the selection of the reform options that resulted in the maintenance of disparities through the 1995-2005 programme were found in the history, culture and political setting of Samoa. Because of the small size and ethnic and cultural homogeneity of the population, the evaluation was based on the theories of Pierre Bourdieu. Bourdieu’s concepts of field practice and habitus showed how the policy options included in the reform programme were influenced by an underlying habitus that generated the desire for change but also constrained the achievement of the stated aim of a “system characterised by equity”. The research showed how the historical background to the patterns of advantage within the system and the structure and patterns of advantage that resulted from the reforms continued beyond the reform.

    View record details
  • Factors affecting cassava adoption in Southern Province of Zambia : a case study of Mazabuka District : a thesis presented in partial fulfilment of the requirements for the degree of Master of Applied Science in Agri-Commerce at Massey University, New Zealand

    Phiri, Tionenji (2011)

    Masters thesis
    Massey University

    Southern Province of Zambia is a drought prone area and the main crop that is grown is maize which requires a high amount of rainfall. As a result maize does not do well in the area and there are frequent food shortages. The Government and Non- Governmental Organisations (NGOs) have been promoting cassava technology which is drought tolerant to improve the food security in the area. However, the adoption of cassava technologies has been low. The findings of this study will inform the development of more effective strategies to improve food security in southern province of Zambia and it has done this by exploring the cassava promotion programme. A single case study was used to investigate the factors that affect cassava adoption in Mazabuka district. Purposive and snowball sampling methods were used to select participants for interviews and observations. 40 farmers who included opinion leaders and 6 key informants were interviewed. The data was analysed using qualitative data methods. The results of the study indicated that although a small number of farmers continue to grow cassava, the cassava promotion programme was a flawed programme because cassava did not meet the needs of the majority of the farmers. There was a mix of complex and interrelated factors that affected the adoption of cassava. These included internal and external factors to the farm and farm household and those related specifically to the characteristics of cassava relative to the farmers’ existing crop of maize. Cassava is a substitute crop to maize. The result of the study indicated that the farmers’ adoption decision was based on the fact that they wanted a crop that would not only meet their food needs but also income. Cassava is a substitute crop and the farmers compared it with maize, an existing crop, which provided them with both food and income. Processing facilities and a market supported by government policy existed for maize and not for cassava. Land tenure was the internal factor, but not as a result of the length of time the lease was held, but because of the conditions imposed on the leasers in terms of crops they were able to grow. The most important factors were external factors and these included government policy and an aspect of extension service delivery. A competitive government policy that supported processing and marketing facilities for maize, undermined cassava, for which there was no processing facilities and only a small local market. Lack of training and knowledge amongst the local government agricultural extension personnel as to how to grow and process cassava impacted also on farmers’ knowledge and hence adoption of cassava. Although the inputs for growing cassava were provided for free, they were supplied at the wrong time and this impacted also on farmers’ willingness to grow the crop. The research highlights the importance of using bottom-up and not top down approaches in food security programmes. The results suggest that it is important for food security policy and development interventions to understand the needs of farmers in terms of food, income and livelihoods.

    View record details
  • Factors affecting sustainability of agricultural cooperatives : lessons from Malawi : a thesis presented in partial fulfillment of the requirements for the degree of Master of AgriCommerce at Massey University, New Zealand, March, 2011

    Nkhoma, Agnes Towera (2011)

    Masters thesis
    Massey University

    Incorporation of small-scale farmers into agricultural commercialization has led rural communities to form cooperatives for better access to markets. However, sustainability of these cooperatives has been a great challenge. This thesis explores the sustainability problems affecting agricultural cooperatives in Malawi, and develops testable proposition for use on a larger sample. A multiple case study was used to investigate factors that contribute to the unsuccessful performance of agricultural cooperatives. Four cooperatives were selected by a combination of market failure and a-priori sustainability criteria. Basing on the market failure assumptions two cooperatives, from a district close to the major city of Lilongwe and two from a district far away from the city, were selected. In each district one sustainable and one less sustainable cooperative were selected based on the ranking prepared by Ministry of Agriculture and Food Security. The sample was further validated by the experts from local NGOs. Sixteen face to face interviews were conducted on location. Members of cooperatives, board members, the management of cooperatives and key informants were interviewed. It was found that most farmers joined cooperatives to improve their livelihood, through better access to capital and product markets, and for family food security. The farmers have managed to obtain input loans at small scale, despite their dissatisfaction with their cooperatives failure to access product markets. The general consensus for the participants in all the four cooperatives was that in their current state these cooperatives are not sustainable. Although, all the members interviewed were satisfied with the idea of having a cooperative and perceived it to be a good idea for addressing their needs, they were skeptical of their survival. The participants highlighted lack of market access, poor governance and a lack of managerial skills as the main problems affecting their cooperatives. These problems are aggravated by the complexity of the market environment in which these cooperatives are operating, that underscores the significance of the managerial capabilities and the cooperatives capacities. The study indicated that Malawian agricultural cooperatives are essential but still need a lot more support in the area of produce marketing. These findings draws propositions in relation to factors which led to Malawian agricultural cooperatives sustainability problems that can later be tested on a large sample in the other parts of the country or region. From such experiences and lessons, it is recommended to establish an apex organisation or secondary level cooperative at district level to address governance, management and market access problems, in order to improve the performance of cooperatives. Further, community sensitization is needed to increase memberships. In addition, policy interventions such as provision of the infrastructure necessary for accessing market information and supportive regulatory framework that would allow competitive market environment.

    View record details
  • A field investigation into the relationship between LA90 and LAeq wind turbine sound level descriptors in New Zealand : a thesis presented in part fulfilment of the requirements for the degree of Master of Philosophy (Science) majoring in Environmental Acoustics at Massey University, Wellington, New Zealand

    Hannah, Lindsay John (2011)

    Masters thesis
    Massey University

    Wind turbine generator acoustics is an issue for communities as it is people within these communities that occupy dwellings. The current New Zealand wind turbine standard NZS6808:2010 Acoustics – Wind Farm Noise, places priority on received sound pressure levels at dwellings remote from the wind turbine rather than from sound emission at the wind turbine generator itself. As part of assessment under NZS6808:2010, background noise levels are required to be measured [as LA90] at selected relevant receiving locations off site before a wind farm site can be developed. Allowable wind turbine design sound limits are then derived [as LAeq] from a comparison of the predicted wind turbine sound pressure levels and the actual measured average background noise at the nominated off site receiving location[s]. A disparity arises with the use of two different sound level descriptors used for assessment under the standard, namely the statistical LA90 versus the LAeq energy average sound level descriptors. In order to account for the possible variation between the LA90 and LAeq sound level descriptors NZS6808:2010 requires LAeq predicted sound pressure levels to be ‘converted’ to received LA90 sound pressure levels as part of the acoustic prediction process and hence NZS6808:2010 states the predicted LAeq sound pressure levels at any receiver location are to be treated as equivalent to the LA90 value. At the time of commencing this study the [then] current New Zealand wind turbine standard NZS6808:1998 Acoustics – The Assessment and Measurement of Sound from Wind Turbine Generators stated that background noise levels were ‘typically 1.5 dB to 2.5 dB’ lower than the predicted LAeq sound pressure levels for wind turbine generator sound. Unlike the current standard, NZS6808:1998 did not provide any means to account for the disparity between the background noise levels and predicted wind farm sound levels as part of the wind farm assessment process. A key implication being that under NZS6808:1998 wind turbine sound could potentially exceed the allowable 40 dBA design sound limit [or average background noise level + 5 dB] by up to a further 2.5 dB and still remain in compliance with the limits recommended under the NZS6808:1998. The impetus and motivation behind this study has consequently been to endeavour to quantify the variability between wind turbine generator sound descriptors [LAeq and LA90] both on the wind farm site and at a remote receiver dwelling location where people actually reside. The research outcome is relevant as at the time of commencing this thesis NZS6808:1998 was being reviewed by experts and practitioners in the area of wind turbine acoustics. This review included assessing any differences in sound level descriptors. This review provided the incentive for the thesis being particularly valuable, unique and practical so far as any actual measured field results were relative to wind turbine generators in New Zealand and the New Zealand Standards operating environment. In order to carry out the evaluation between LAeq and LA90 sound level descriptors an assessment based around a semi-empirical field study of objective field measurements and subjective observations was conducted at two wind farms in the lower North Island of New Zealand. The study assessed present day, commercial class, horizontal, three bladed wind turbine generators located over heterogeneous terrain. The principal implication of the study related to the collection of uncontaminated wind turbine sound level samples. A raw data set of 11,150 [10 minute LAeq/LA90 sound level samples] were collected over a 12 month period. From the total sample, merely 39 [or less than 2% of the total raw sample] were actual uncontaminated wind turbine sound samples only. The conclusion here is that due to the high number of intervening variables it is a challenge to collect a large sample set of uncontaminated wind turbine sound data. Based on the data collected, it could potentially take several years to collect a suitable uncontaminated sample of say 1,500 [10 minute samples] from wind turbine sound only at remote locations off the wind farm site using such methods. Data collection and analysis was not an issue on the wind farm site itself due to the measurement location and wind turbine being in close proximity. The results of the field study illustrated that based on the final data set of 10 minutes sound level sampling [n=39] the overall mean sound level difference [LAeq - LA90] for wind turbine sound was 2.4 dB at a remote residential location some 1200m from the wind farm site. The overall mean sound level difference for wind turbine sound levels based on the wind farm was 1.4 dB [at the nominated Ro location]. As a result of the study’s findings it is concluded that although the field data indicated a quantifiable level difference between the two sound level descriptors the current wind turbine noise standard [NZS6808:2010] rightly removes any uncertainties by stating that LAeq = LA90 when carrying out the assessment process. Therefore the removal of any uncertainty is chiefly due to the fact that although a quantifiable level difference between the two sound level descriptors was achieved for this study the sound level difference is prone to change and any precise or exact level difference is therefore a factor of the wind turbine generator models tested site conditions and related intervening variables.

    View record details
  • Offsite manufacturing as a means of improving productivity in New Zealand construction industry : key barriers to adoption and improvement measures : a research thesis submitted in fulfilment of the requirements for the degree of Masters of Construction Management at Massey University, Albany, New Zealand

    Shahzad, Wajiha Mohsin (2011)

    Masters thesis
    Massey University

    Off-site manufacturing (OSM) of building components could be leveraged to improve the reported low productivity trend in the New Zealand (NZ) construction industry. Despite the numerous known benefits of OSM, the uptake of the technology in the industry has been discouragingly low. Previous studies offer little help in terms of prioritising identified barriers to the uptake of OSM. As a result, improvement efforts have been daunted by numerous barriers in the face of limited resources. This study aims to contribute to bridging the gap in the extant literature by identifying and prioritising the key constraints to the industry-wide uptake of prefabrication and the improvement measures. Through a nation-wide survey of consultants, contractors, employers and manufacturers, feedback was received and analysed using the multiattribute analytical technique. Results show that the broad categories of constraints to the adoption of prefabrication in NZ are (in order of decreasing impact and relative contributions): industry and market culture (16.2%), skills and knowledge (15.5%), logistics and site operations (14.8%), cost/value/productivity (14%), supply chain and procurement (13.7%), process and programme (13.6%), and regulatory (12.2%). The subcomponents of the broad constraint categories and their relative levels of impact on the uptake of the technology were reported. In addition to addressing the key barriers identified in the study, further measures for improving the uptake of the technology in New Zealand include promotion by client through specifying OSM in the design briefs, improved education and training on the use of OSM, more marketing/ awareness campaign on the benefits of the technology and better supply chain management and transportation logistics. To enable a methodical evaluation of the marginal value achievable by the use of a variant of OSM over and above that of the traditional stick-built system at the design and life-cycle phases of the procurement process, a decision support model was developed. The model incorporates the key performance indicators (KP1s) underlying clients’ value system at the development and operational phases and compares the extent to which each variant of OSM delivers each value criterion relative to the conventional system. The sum of the marginal values at each phase of the procurement iii | P a g e system provides the rationale basis for choosing either the OSM variant or the conventional system based on the approach that delivers the highest marginal value. The model application to real life project was demonstrated using the modular variant of the OSM compared to the conventional stick-built system. Results of the model application at the development phase shows that the OSM was more beneficial to the client than the conventional system with an overall marginal value of 34% relative to the conventional construction approach. Individual results showed 22% improvement in the completion time for the project, 9% improvement in quality and 3% reduction in the carbon footprint at the development phase. However, the technology was found to be 2.4% more expensive than the traditional stick-built system. Results of the model application at the operation and life-cycle phases also show that the technology achieved superior value compared to the conventional stick-built system. The overall marginal value achieved by the modular OSM application at the operation phase was 49% compared to the traditional stick-built system; this comprised 23% reduction in the running and maintenance costs, 18% reduction in the maintenance frequency of the structure and fabric, and an annual 8% reduction in the carbon footprint. Overall, the use of modular variant of the OSM was found to deliver superior value to clients compared to the conventional system at the development, operational and lifecycle phases of the procurement process.

    View record details
  • An integrated literature review of the role of the nurse practitioner in the emergency department

    Eden, Sheryl M (2011)

    Masters thesis
    University of Otago

    A dissertation in partial fulfilment of Master [of] Health Sciences (Clinical) through [the] University of Otago, [Dunedin, New Zealand]. Description: v, 115 leaves : forms ; 30 cm. Notes: "January 2011." Thesis (MHealSc)--University of Otago, 2011. Includes bibliographical references.

    View record details
  • An Exploration into Sponsor Relations: How Value is Perceived by Businesses in Art Sponsorship Relationships

    Tyrie, Anna (2011)

    Masters thesis
    University of Otago

    While a vast number of studies have explored exchange dimensions between two entities as a means of value extraction, little attention has been paid to the value which an organisation can receive from a sponsorship relationship. Current literature provides relatively little insight into the sponsorship exchange relationship, particularly that within the arts sector. Reports suggest that the art sponsorship sector will grow a further 40% between 2008 and 2012, prompting that further information is required (Key Note, 2007). The purpose of this research is to gain insight into whether the relationship influences and affects value derived from a sponsorship, as perceived by the sponsoring business. The Literature review provides a comprehensive overview of the literature pertaining to sponsorship and social exchange theory. The review explains the relevance of exchange and social exchange theory, as means of understanding how the relationship influences upon and effects relations between two exchanging parties. Through this process, a gap in knowledge was identified which guided the primary research. The research applied a qualitative, exploratory manner, in order to explore business perceptions of their art sponsorship relationship(s). The research involved interviewing seven businesses, from a range of industries and sizes, on their perceptions and experiences with art sponsorship. The interviews were transcribed and coded, after which a thematic analysis was applied in order to generate meaningful patterns. This process identified five categories which reflected the data and the research objectives. The findings suggest that the perceived value within a firm’s art sponsorship is heavily reliant upon the relationship, where value is derived through the culmination of various areas such as a firm’s motivations, expectations, practices, experiences and perceptions. The thesis provides several models which explain how value is derived and how value derivation alludes to greater ideas, like the lifecycle of a sponsorship relationship.

    View record details
  • The effects of digestion resistant carbohydrates on the colon microbiota and colon tissue transcriptome of weanling rats

    Young, Wayne (2011)

    Doctoral thesis
    University of Otago

    Digestion-resistant carbohydrates (DRC) in the diet pass to the terminal ileum and large bowel where they may be fermented by resident bacteria. The bacterial communities in the bowel of young animals undergo dramatic shifts in composition following weaning. These compositional and associated biochemical changes may have long-lasting impacts on the host. However, the mechanisms by which diet induced changes in the microbiota influence host physiology requires further investigation. This study examined whether bacterial community compositions could be engineered by supplementing the diet of newly-weaned rats with different forms of DRC and the subsequent effects these altered microbial communities had on host physiology. Newly weaned conventionally raised or germ-free male 21-28 day old Sprague-Dawley rats were fed a basal diet or basal diets supplemented with DRC at concentrations up to 5% for 14 or 28 days. Colonic digesta was collected from each rat for analyses to determine short chain fatty acid (SCFA) concentrations and to compare bacterial community structure by temperature gradient gel electrophoresis (TTGE) and 454 pyrosequencing analysis of the V3 hypervariable region of the 16S rRNA gene. DRC induced alterations in the host transcriptome were assessed by microarray analysis of RNA extracted from colon tissue. Feeding DRC significantly increased concentrations of SCFA in the colon digesta of young rats. The DRC induced changes in SCFA concentrations were also accompanied by alterations in the colonic microbiota structure. Each type of DRC altered the microbiota in a distinctive manner, which could be clearly differentiated from those of rats fed the basal diet. Feeding DRC also resulted in more uniform microbiota compositions compared to the basal diet. The alterations in microbiota composition were associated with changes in host colon gene expression profiles. Each form of DRC altered colonic gene expression in a distinct manner with profiles from rats fed the same diet showing greater similarity than those fed different diets. Differentially expressed genes in the colon were involved in a number of biological functions including energy metabolism, immune function, and cellular growth and differentiation. Comparisons of the effects of DRC on host gene expression between conventionally raised and germ-free rats showed that the resident microbiota was a determining factor of the host response to DRC. Feeding DRC to conventionally raised rats resulted in the differential expression of different sets of genes compared with feeding DRC to germ-free rats. The results of this study show that the bacterial communities in the colon of newly-weaned rats can be engineered by supplementing the diet with DRC. Using this approach, unique bacterial communities with enhanced fermentative capacity, increased uniformity, and distinct effects on host gene expression were selected. The findings from this study provide support and future scope for the development of different dietary supplements that target different parameters of large bowel function.

    View record details
  • The effect of intermittent and continuous hypoxia on cerebral vascular function in humans

    Peebles, Karen Clendon (2011)

    Doctoral thesis
    University of Otago

    The extent to which systemic hypoxia may compromise cerebrovascular function is likely to depend on the intensity and duration of the hypoxic insult. This thesis presents four studies that used a range of intermittent and continuous hypoxic paradigms that examined i) whether hypoxia alters cerebrovascular reactivity during acute alterations in the partial pressure of end-tidal CO2 (PETCO2) and end-tidal O2 (PETO2); and ii) whether reductions in cerebrovascular reactivity were mediated by changes in nitric oxide (NO). As a secondary goal, the impact of alterations in peripheral chemoreceptor (PCR) activity on cerebrovascular function, and on ventilatory (VE) sensitivity were also explored. Blood flow velocity in the middle cerebral artery (MCAv) and cerebral oxygenation, provided indices of cerebrovascular function. Study one demonstrated that acute hypercapnia was associated with the net release of NO from the brain. Therefore, in subsequent studies, cerebrovascular reactivity to hypercapnia, along with complementary NO metabolites (plasma nitrite and NOx [nitrite + nitrate]), was used as a surrogate index of NO bioavailability. Study two examined the effects of chronic (years) intermittent hypoxia (CIH) on cerebrovascular function in patients with severe obstructive sleep apnoea (OSA, apnoea-hypopnoea index > 30 events/h). When compared to a group of appropriate controls, hypercapnic cerebrovascular reactivity was reduced in OSA patients. Since plasma NOx was also reduced, it would seem feasible that this compromise in reactivity was due to a reduction in NO bioavailability. Nevertheless, correlative analysis revealed that the presence of OSA was not the only factor associated with a reduction in hypercapnic cerebrovascular reactivity; a novel finding was that increased age and body mass index were linked as well. Alleviating CIH with 5-6 weeks of continuous positive airway pressure (CPAP) caused no alterations in hypercapnic cerebrovascular reactivity or NO metabolites, but caused a small (4 mmHg) reduction in mean arterial blood pressure (MABP). Study three examined the effects of short-duration intermittent hypoxia [SDIH] and short-duration continuous hypoxia [SDCH]) on cerebrovascular function in healthy participants. For SDIH, participants performed 2 h of repetitive hypoxic apnoeas to mimic OSA (20 s apnoeas; nadir peripheral oxygen saturation [SpO2] ~84%; 30 times/h). For SDCH, participants were exposed to a single hypoxic episode matched in duration (i.e., 20 min) and intensity (i.e., SpO2) to SDIH. Cerebrovascular reactivity and ventilatory sensitivity were assessed during acute PETCO2 alterations under hyperoxic and hypoxic rebreathing in order to provide insight into PCR activity. SDIH (but not SDCH) led to a selective reduction in frontal cerebral oxygenation during hypoxic rebreathing; no concomitant alterations in MCAv or in NO metabolites were observed. One interpretation of these findings is that oxygenation of the frontal lobe was compromised to ensure perfusion of more vital regions of the brain (e.g., brainstem) after SDIH. SDCH (but not SDIH) led to elevations in MABP at rest and MABP reactivity during hypoxic but not hyperoxic rebreathing, likely mediated via PCR activation. No concomitant alterations in VE sensitivity during hypoxic rebreathing were observed possibly due to different rates of recovery for MABP and VE post SDCH; there were no alterations in VE sensitivity during hyperoxic rebreathing. Lastly, in study four, the effect of ~3 weeks of continuous hypoxia on cerebrovascular function and ventilatory sensitivity was examined in healthy sea-level participants following ascent to 5050 m. The main findings were that ascent to 5050 m led to an increase in resting MCAv, and enhanced MCAv reactivity during hypoxic and hyperoxic rebreathing. Alongside a high-altitude induced increase in resting VE , these cerebrovascular responses might serve to maintain oxygen delivery to the brain in the face of hypoxia until other adaptive mechanisms (e.g., an increase in capillary density) that aid oxygen extraction become manifest. Collectively, these findings indicate that the precise effect of systemic hypoxia on cerebrovascular function was contingent on the hypoxic paradigm. Shorter durations of hypoxia (i.e., 2 h intermittent hypoxia and ~3 weeks continuous hypoxia) evoke cerebrovascular responses that may serve to preserve oxygen delivery to vital regions of the brain whereas longer durations of intermittent hypoxia (i.e., CIH, in patients with OSA), is associated with a reduction in cerebrovascular function that may compromise brain function. Furthermore, the findings of this thesis suggest that: i) a reduction in NO bioavailability may contribute to a reduction in hypercapnic cerebrovascular reactivity in patients with OSA; and ii) that alteration in PCR activity may contribute to the elevated MABP after 2 h of continuous hypoxia. Irrespective of the hypoxic paradigm, the cerebrovascular, cardiovascular and ventilatory responses to acute alterations in PETCO2 and PETO2 are complex and inter-related.

    View record details
  • Are we learning from past practice: The potential for follow-up as an environmental management tool in New Zealand

    Rendall, Chris (2011)

    Masters thesis
    University of Otago

    All development has the potential to cause adverse effects to the environment. Worldwide, environmental concern regarding these effects has significantly increased over the past forty years. This has led to the implementation of environmental legislation and associated requirements for Impact Assessment (IA). The effectiveness of this legislation and other aspects of the effects management framework in protecting the environment have, however, been questioned. The current research firstly examined IA, to identify whether this process was capable of achieving desired environmental outcomes. It found that a primary factor in determining if IA could be an environmental management tool depends on whether follow-up is included in this process. Namely, this includes the use of monitoring, auditing, management and communication of the actual effects of a development. This research highlighted that the IA process can achieve desired environmental outcomes but that it relies on legislation, policy and political support to be effective. In New Zealand, the environmental effects of development are managed, primarily through the Resource Management Act 1991 (RMA). This process was examined and it was identified that while the RMA provides requirements for environmental management, through the use of monitoring and management provisions, these are seldom used by local authorities. Therefore, the environmental effects of development are not currently being effectively managed. This conclusion was supported by key informants’ comments. However, the literature on planning documents and the effectiveness of Assessments of Effects on the Environment (AEEs) indicated that the quality of both have improved since the implementation of the RMA. In New Zealand, the primary means of identifying ways to mitigate environmental effects is through an AEEs, which provide IA in New Zealand. As noted above, follow-up is a key element of an effective IA process. The only component of follow-up that is commonly used in New Zealand is monitoring, which is not used to assess the actual effects of the development but rather, to ensure compliance with consent conditions. A number of key informants identified that currently, the environmental effects of development are not effectively managed and many considered that the application of follow-up would assist in improving such management. Questions on how and in what contexts follow-up should be implemented elicited a broad range of responses from key informants, and these responses appeared to link to their areas of work. Those involved in urban development stated that the overall effects (i.e. plan effectiveness, and general detractions from environmental quality) were key areas to be followed-up. However, key informants involved in large scale developments considered that follow-up should occur as part of the project development/implementation process thus allowing ongoing management. The range of opinions highlights that further research would need to be undertaken before any modifications are made to Schedule 4 or plan monitoring requirements of the RMA. This research outlines that while individuals at local authorities know their job well, they may not understand the complexities and wide ranging effects of large developments. This is further impacted by the siloed nature of planning departments. The research suggests that the use of a more integrated approach to effects management may be required. Oversight committees consisting of representatives of stakeholder groups, like that established for the BHPB Etaki Mine, may be the solution to these management issues.

    View record details
  • Controls on slope-to-channel sediment coupling in a small, largely deglacierized alpine catchment, Southern Alps, New Zealand.

    Beel, Casey Robert (2011)

    Masters thesis
    University of Otago

    Channel sediment transfer patterns in alpine environments are an integrated signal that reflects both channel sediment sources and sediment input from extra-channel slopes. The degree of slope-to-channel sediment connectivity is controlled by several factors, amongst them differences in the magnitude and frequency of rainfall events, particle size, sediment availability and surface maturity. However, there has been limited work on the development of slope-to-channel coupling in deglaciated alpine environments over time. Characterising the controls on slope-to-channel connectivity in this environment may result in a better understanding of how landscapes ‘relax’ from perturbation. Channel turbidity was measured using custom built iHOBS turbidimeters at two gauging stations, one above a hydrologically connected slope and one below it in the c. 10 km2 Hoophorn Valley, a largely deglacierised basin in the Southern Alps, New Zealand. On this hydrologically connected slope an array of 30 erosion pins was used to measure surface lowering rates on the slope and eight custom built Gerlach troughs were installed in ephemeral slope channels to trap surficial material mobilized during rainfall events. Discharge-suspended sediment concentration hysteresis patterns at the two gauging stations in the main stream channel were used to indirectly infer sediment coupling between the hydrologically connected slope and the main stream. During the study period, a total of 948 t of suspended sediment was transported through the channel at the upstream site and 715 t through the channel at the downstream site. During rainfall events, episodes of high discharge resulted in transfer of 75% of the total suspended sediment load through the upstream site and 50% through the downstream site. The total mass of sediment eroded from the dissected slope was estimated to be c. 3 t for the study period. Sediment mobilisation was confined to rainfall events with increasing particle sizes trapped with increasing event magnitude. Less than 1% of the particle size distribution of all samples collected during these events was classed as fine sediment, suggesting these sediment sources on the slope were exhausted. Channel suspended sediment transfer patterns during rainfall events were dominated by clockwise hysteresis where sediment concentration peaked before discharge. This pattern was interpreted as representing short distance remobilisation of fine sediment from within the channel, supporting the likelihood of limited input of fines from slopes. The data suggests, therefore, that slope-to-channel connectivity in this environment is dominated by coarse sediment, where there is active coupling. The lack of fine sediment sources on slopes within the basin suggest that since deglaciation there has been a relative decline in fine sediment slope-to-channel connectivity due to source exhaustion and a shift to episodic coarse sediment connectivity. This shift is likely associated with a contemporaneous change from a glacial control on fine sediment production and runoff to a rainfall controlled system, where mechanical weathering of bedrock continues to produce coarse material for transport from slopes to channels.

    View record details
  • Training and detraining effects on familial insulin resistance, muscle fibre type, and performance

    Schofield, Katherine L (2011)

    Masters thesis
    University of Otago

    Introduction: Chronic hyperinsulinemia affects muscle, and may advantage speed and power athletes. Hyperinsulinaemia is associated with shifts in expression of myosin heavy chain isoforms, and muscle fibre type resulting in a faster contractile profile (I→IIa→IIb). Insulin sensitivity increases with endurance training, however, there are limited studies on insulin sensitivity with resistance training and detraining. The aims of the present study were to examine insulin sensitivity, skeletal muscle transitions and strength in offspring of Type 2 diabetics, in comparison with normal control subjects, after resistance training and detraining. Method: Six (1 male, 5 female; 21.3 ± 1.8 yr, 164.7 ± 4.6 cm, 62.2 ± 7.1 kg, body mass index (BMI) 22.3 ± 2.5, mean ± SD) familial insulin resistant (FIR) and 10 (4 male, 6 female; 23.0 ± 2.9 yr, 170.1 ± 10.4 cm, 70.0 ± 13.2 kg, BMI 23.8 ± 2.6, mean ± SD) controls (C) completed 9 wk of resistance training (squat, leg press, leg extension, leg curl and box jump exercises) and 9 wk detraining. Measures at baseline (T1), after training (T2) and after detraining (T3) included an oral glucose tolerance test, muscle biopsy and performance tests (3RM; standing squat jump [SSJ], Wingate test, and a force-velocity curve [FVC]). Mixed model and correlation analyses were conducted. Results: There was a significant increase in 3RM values in all exercises, vertical jump (SSJ) and peak power output (PPO) from T1 to T2 (p < 0.05). FVC moved up and right with training (p < 0.05). No significant fibre type changes occurred with training in either C or FIR. FIR reduced insulin area under the curve (AUC) to a greater extent than C with training (65.7 ± 43.4 to 43.4 ± 15.1 vs. 32.7 ± 13.3 to 32.9 ± 14.0 pmol.ml.min-1, resp., p = 0.05). There were reductions in 3RM in all exercises, with detraining (p < 0.001), and decreases in peak moment of force in FVC (p < 0.001), but no change in SSJ and PPO (p = 0.097, p = 0.439, resp.). Detraining decreased percentage type I and increased percentage type II fibres (p = 0.005, p = 0.031, resp.), although no differences in fibre type adaptations or performance were observed between groups. Detraining increased percentage MHC IIx (p = 0.026) and insulin AUC (p = 0.031), with a larger insulin AUC in FIR than in C (p = 0.018). Conclusions: Resistance training produces similar increases in strength in both FIR and C, and decreases in strength with detraining. However, FIR exhibit a greater training effect to reduce insulin AUC and, in contrast to controls, an increase with detraining. While this population did not show clinical signs of diabetes, resistance training can increase insulin sensitivity and may reduce future risk of Type 2 diabetes amongst individuals with mild familial insulin resistance.

    View record details
  • Niche partitioning in the Fiordland wrasse guild

    Davis, Jean (2011)

    Masters thesis
    University of Otago

    Investigating the parameters of niche space for marine organisms is useful for identifying their place in the food web and understanding community dynamics. The range of biological and physical gradients found along the fiord axis in Fiordland, NZ offer a unique setting that is well suited for defining aspects of niche space. The purpose of this thesis was to define the characteristics of niche space of four common species of wrasse found in Fiordland, including spotties (Notolabrus celidotus), scarlet wrasse (Pseudolabrus miles), banded wrasse (Notolabrus fucicola) and girdled wrasse (Notolabrus cinctus). Fish were sampled from three paired inner and outer fiord sites in Doubtful Sound, Thompson/Bradshaw Sound and Dusky Sound. Gut contents analysis, stable isotope analysis and morphological analysis of facial features associated with foraging strategy were applied in an effort to characterize diet as an indicator of biological niche space. Fiordland-wide SCUBA surveys of abundance and distribution were correlated with both physical and biological gradients to observe evidence of habitat partitioning. Finally, age and growth analysis was evaluated to assess evidence of trade-offs in life history strategy. Based on these indicators, spotties were found to occupy a significantly different niche space than scarlet wrasse, banded wrasse and girdled wrasse. High niche overlap was found among these other species, with some differences in prey field and microhabitat partitioning. This pattern is mainly attributed to the fact that spotties were observed to be a highly plastic species (generalist), exploiting a wide range of resources over the length of the fiord axis. Conversely, other wrasse species exploited a relatively narrow range of resources (specialists), preferring highly productive kelp forest habitat near the outer coast. Spotties were found to partition niche space between inner and outer fiord environments, consuming a less nutritious diet in the inner fiord by exploiting both terrestrial sources of carbon and alternate trophic levels. In conclusion, the role of wrasse species as pervasive, abundant invertebrate predators in the Fiordland ecosystem indicates they likely play an important role in maintaining ecosystem structure. Though niche partitioning occurred among species and over spatial gradients, outer coast areas appeared to support the most valuable, high quality habitat for Fiordland wrasse species.

    View record details
  • Measurement and perceptions: Physical activity in people with low back pain

    Perry, Meredith Amy Claire (2011)

    Doctoral thesis
    University of Otago

    Physical activity (PA) is recommended for the management of low back pain (LBP). This research was undertaken to: establish the use of accelerometers as an outcome measure in studies investigating the free-living PA of people with LBP; explore the free-living PA of people receiving physiotherapy for LBP; and compare patterns of PA between people with acute low back pain (ALBP) and people with chronic low back pain (CLBP). PA was measured with the RT3 accelerometer (Stayhealthy Inc., Monrovia, California, USA) which is an objective measure of PA. In addition, perceptions of being physically active with LBP and the coherence between the lived experience of LBP and physiotherapy management were explored. A review of PA and LBP literature found that while ‘advice to stay active’ is recommended, there is a paucity of research exploring the free-living PA of people with LBP with an objective measure, such as an accelerometer. It is unknown if free-living PA is altered in people with LBP compared to healthy individuals. Likewise, the psychometric properties of many accelerometers are also unknown and this may account for some discrepancies in results. A pilot study was undertaken in healthy volunteers (N = 21) to determine the minimum number of days per week of valid RT3 data required to reliably estimate PA, and the validity and utility of the RT3. The RT3 was found to have acceptable utility and good validity, and a minimum of four days of RT3 data are required to reliably assess PA. A mixed methods (MM) study explored: the responsiveness of the RT3 to measure change in PA, compare patterns of PA between people with ALBP or CLBP (N = 111); and semi-structured interviews were conducted with a sub-group of the LBP participants to explore perceptions of PA (N = 13). The RT3 demonstrated limited responsiveness to perceived change in PA, measured with the Global Rating of Change (GROC), at week six only; perceived PA and measured PA appear to be different constructs. A significant interaction between LBP and week of PA measurement was found. Neither LBP group met the recommendation for sustained bouts of moderate intensity PA per day. Interviewees knew that PA was an important aspect in the management of their LBP. However, being active was dependent on perceived control and this was unrelated to LBP classification. The use of “trial and error” strategies when increasing PA resulted in a flare of LBP, the reinforcement of negative PA beliefs and behaviours, and poor treatment coherence. Further research into the design and psychometric properties of accelerometers is warranted. People with ALBP have different PA patterns to people with CLBP; yet both groups demonstrate an inability to endure sustained and repetitive bouts of moderate intensity PA. People with LBP are unsure how to return to habitual PA. Physiotherapists may need to consider treatment coherence, and provide more time and support for changing unhelpful perceptions and PA behaviours. To conclude, perceptions of PA are not the same construct as objectively measured PA, but both constructs are important.

    View record details
  • Epidemiological validation of a Malay version of the Child Perceptions Questionnaire (CPQ11-14) in Brunei

    Haji Mohamed, Haji Amirul Rizan (2011)

    Masters thesis
    University of Otago

    Background: Oral health-related quality of life (OHRQoL) instruments are being used with increasing frequency in oral health surveys. One such instrument is the Child Perceptions Questionnaire (CPQ11-14), developed in Toronto as a measure of OHRQoL specifically for 11-to-14-year-old children (Jokovic et al, 2002). It aims to improve the description of children's oral health, while taking into consideration the importance of psychological aspects in the concept of health. As the original version of this questionnaire was considered long (37 items), shorter forms were developed with 8 and 16 items to facilitate its use in the clinical settings and population-based oral health surveys (Jokovic et al, 2006). The developers of the CPQ¬11-14 have determined the psychometric properties of the long-form and the short-forms CPQ¬11-14 to be satisfactory, but state that these measures must be validated and employed in other cultures, involving clinical and population-based samples of children and adolescents in different countries. The short-form measure has been tested and validated in a representative population sample of schoolchildren in New Zealand (Foster Page et al, 2008). On the other hand, the long-form CPQ11-14 has been shown to be valid and reliable in a number of different countries including Canada, the United Kingdom, New Zealand, Uganda, Saudi Arabia, Australia, Brazil, Hong Kong and Denmark. However, neither the long-form nor the short-form CPQ11-14 has been translated into a Malay (Bahasa Melayu) version and tested in the South-East Asian region. Schoolchildren are the main target group for public oral health services in Brunei. Until now, data on the Brunei population’s oral health included only the clinical status of oral diseases. Although the focus of the Brunei Ministry of Health has shifted from being disease-oriented to emphasising wellness and the maintenance of the quality of life of the population, a measure of OHRQoL appropriate for use in Brunei has not been available. Therefore, the aims of the current study were: 1. to produce a Malay version of the short-form CPQ11-14; 2. to determine the construct validity of the CPQ11-14 in Brunei; and 3. to determine the discriminative validity of the CPQ11-14 by assessing its ability to distinguish between schoolchildren with and without dental caries and malocclusion. Method: Ethical approval was granted by the Medical and Health Research and Ethics Committee, Brunei Ministry of Health. Five hundred and sixty-nine 11-14-year-old (Year 6) children in nine government primary schools were asked to participate. Parents and caregivers of the children in the study sample were then mailed (through their class teachers) an information sheet about the study, together with an enclosed consent form. A Malay version of the short-form CPQ11-14 was derived through a forward-backward translation process. The questionnaire was then piloted on 20 schoolchildren and refined for ease of use. Prior to clinical examination, all participants completed a copy of the Malay short-form CPQ11-14. The children were examined for dental caries experience (using the DMFS) and for malocclusion (using the Dental Aesthetic Index) by a single examiner (ARM). Both clinical data and data from CPQ11-14 were entered into a Microsoft Excel spreadsheet, and subsequently imported into SPSS. The psychometric properties of the Malay short-form CPQ11-14 were evaluated in terms of internal consistency, construct validity and discriminant validity. Test-retest reliability was assessed in a subgroup of these children (n = 48). Results: A total of 457 children (mean age of 11.1 years, range = 10 to 14 years) were examined, giving an effective participation rate of 80.3%. The prevalence of dental caries in the permanent dentition was 44.4%. The mean dmfs and DMFS of deciduous and permanent dentitions were 1.51 (sd, 3.31) and 1.96 (sd, 3.74) respectively. About one-fifth had 4 decayed surfaces in either dentition. The DAI scores ranged from 17 to 91, with a mean of 31.4 (sd, 8.7). The distribution of participants across the four treatment need categories was: minor/none, 24.1%; definite, 37.0%; and severe/handicapping, 38.9%. The overall CPQ11-14-ISF16 score ranged from 0 to 43, with a mean of 16.8 (sd, 8.7). The number with the minimum score was minimal, with only 1.1% having a score of zero and there were no children with the maximum score. Construct validity was satisfactory, demonstrating significant associations between the mean CPQ11-14-ISF16 scores and the global ratings of oral health and overall well-being. The CPQ11-14-ISF16 was able to discriminate between different caries status, and there was a significant association between impact prevalence and the number of untreated decayed tooth surfaces in either dentition. Interestingly, the gradient of the scale scores across categories of orthodontic treatment need was in the opposite direction, whereby those in the ‘minor/none’ category had the highest and those in the ‘severe/handicapping’ category had the lowest mean CPQ11-14-ISF16 score and impact prevalence. The Malay short-form CPQ11-14-ISF16 had excellent internal consistency with a Cronbach’s alpha of 0.97 and test-retest reliability ICC of 0.94. Conclusion: The outcome of this study suggests that the Malay short-form CPQ11-14 is a valid, reliable and practical instrument for measuring OHRQoL in 11-14-year-old Bruneian children, although its ability to discriminate among children across the malocclusion treatment need categories seems to be limited. This provides further evidence of the instrument’s psychometric properties and its cross-cultural use. However, these are preliminary findings based on a convenience sample, and further testing in replicated studies involving clinical and population samples of children in various settings is necessary to establish the measurement sensitivity and discriminative properties of the Malay short-form CPQ11-14.

    View record details
  • The Effect of Active Living and Physical Activity on Post-prandial IL-6 and CRP

    Bone, Julia Lizet (2011)

    Masters thesis
    University of Otago

    Aims: Post-prandial increases in inflammatory markers IL-6 and C-reactive protein (CRP) have been observed following high fat and high carbohydrate meals. Inflammation is associated with increased risk of chronic diseases such as cancer. In addition, sedentary behaviour is also associated with negative health outcomes. Meanwhile, elevated IL-6 and CRP have been associated with a negative mood. The study aim was to compare the effects of continuous physical activity to breaks in sedentary behaviour on post-prandial IL-6 and CRP. The secondary aim was to compare the impact of these patterns (as detailed above) on measures of mood states. Methods: Twenty four healthy sedentary participants (15 female, nine male, mean ± SD, age 25.8 ± 5.8 yr, BMI, 23.6 ± 5.0 kg/m2) completed three, 9 h testing days. These were: sedentary (SE), participants remained seated for 9 h; physical activity (PA), participants performed 30 min of exercise at a speed and incline to elicit 60% VO2max prior to the first meal replacement beverage and were then seated for the remainder of the 9 h; active living (AL), participants walked for 1 min 40s every 30 min throughout the day (this equals 30 min of physical activity spread out over 9 h) at the same speed and incline as the PA condition. For each condition participants received three meal replacement beverages at 1, 4 and 7 h. Each meal provided 0.46 g fat/kg BW, 0.54 g protein/kg BW and 1.12 g CHO/kg BW. Venous blood samples were collected at baseline, 4 and 8 h to measure IL-6 and CRP. Mood was assessed using the Brunel University Mood Scale at 0 and 9 h. Results: In the SE and PA conditions there was a post-prandial increase in IL-6 at 4 and 8 h compared to baseline (SE p<0.05). There was no change in CRP from baseline, nor was there a difference between conditions. No correlation existed between mood and CRP. Increases in IL-6 correlated with a more depressed mood. Both PA and SE conditions decreased tension. There was no effect of AL on mood. Conclusions: Interleukin-6 increased 4 and 8 h post-prandially when sedentary. Thirty min of moderate continuous physical activity following an overnight fast and prior to a meal does not decrease the post-prandial IL-6 response. Breaking sedentary behaviour by as little as 1 min 40 s every 30 min attenuates the post-prandial IL-6 response and thereby, may reduce the risk of chronic diseases. Practical applications from these findings include the use of computer prompts or television advertising to promote standing and walking in individuals with desk jobs or when watching television for long periods of time.

    View record details
  • An Epigenetic Analysis of the Human Placenta

    Macaulay, Erin Cuffe (2011)

    Doctoral thesis
    University of Otago

    The human placenta is a highly specialized organ that is responsible for the survival of pregnancy. During its development, placental trophoblast cells invade into the uterine wall to establish a blood supply for the growing fetus. Previous studies have suggested similarities between the invasive phenotypes of trophoblasts and tumour cells; however, a key difference is that trophoblast invasion is under strict control. Given that epigenetic mechanisms have been linked with the silencing of key regulatory genes in cancer, we hypothesized that the epigenetic regulation of first-trimester placental trophoblasts may provide a mechanistic relationship between placental and cancer growth. Further, although the hypomethylated environment within the pseudo-malignant placenta is unique, its role in facilitating placental function is poorly understood. We sought to document placental-specific epigenetic modifications, taking into account that the origin of the placenta is determined during the earliest stages of embryonic development, when the inner-cell mass is first distinguished from the trophectoderm, and when the inner-cell mass further differentiates into the primitive endoderm and the epiblast. A genome-wide methylation analysis was performed using methylated DNA immunoprecipitation (MeDIP) combined with hybridisation to promoter microarrays to identify differentially methylated gene promoters between first-trimester human placenta and peripheral blood DNA. The promoter methylation of 29 candidate genes was then quantified using Sequenom MassARRAY®. Differential methylation patterns were detected in placental tissues compared to both fetal and adult somatic tissues. The relationship between promoter methylation and gene expression was then assessed using real-time PCR and immunohistochemistry. The promoter methylation of one gene, KCNH5, was found to be lineage-specific: low in all tissues derived from the extra-embryonic lineages (trophectoderm and primitive endoderm) and very high in tissues derived from the embryonic (epiblast) lineage. The dichotomous promoter methylation of KCNH5 was found to regulate the lineage-specific expression of alternative gene transcripts. Interestingly, the KCNH5 promoter that is used in tissues derived from the extra-embryonic lineages, and which shows dichotomous methylation, has recently evolved from a SINE retrotransposon that is present in only humans, old world monkeys and apes. To our knowledge, this the first example of a human transcript derived from the insertion of a SINE element. Finally, the lineage origin of the extra-embryonic mesenchyme has been a topic of longstanding debate. The combined epigenetic and expression profiles of KCNH5 in placental villous stroma provide compelling evidence that the extra-embryonic mesenchyme is derived from the primitive endoderm. Retrotransposons are normally silenced by methylation to prevent genome dysfunction. However, the placenta is becoming increasingly known as a tissue in which retrotransposons are actively transcribed. We observed that the absence of retrotransposon-silencing by methylation permitted the emergence of a placental-specific transcript by allowing the retrotransposon to serve as an alternative promoter for KCNH5. Examination of additional retrotransposon-derived genes in the placenta (INSL4 and ERVWE1) confirmed that dichotomous methylation between embryonic and extra-embryonic lineages is a feature of early development. The finding that the retro-elements in these genes have escaped the normal silencing mechanism suggests that they may have functional roles that are unique to the invasive placentas of humans and recent primates.

    View record details
  • Role of NK cells in DC-based immunotherapy of melanoma

    Bouwer, Anthea Lynne (2011)

    Doctoral thesis
    University of Otago

    Natural killer (NK) cells were first identified by their ability to kill tumour or virally infected cells without prior sensitization. In spite of this, the actual role of NK cells in tumour immunotherapy remains controversial. This study therefore set out to investigate the potential of Streptococcus salivarius K12, a gram-positive bacterium that has a history of commercial application as a probiotic in New Zealand, for use as a NK cell adjuvant, applying the therapy using B16.OVA melanoma as a model. To confirm that S. salivarius K12 was able to induce efficient activation of NK cells, I first screened a number of gram-positive and gram-negative bacteria for their ability to induce IFNγ release from NK cells. Using ELISA and fluorescence activated cell sorting (FACS) I found that gram-positive bacteria stimulated a rapid release ( through interaction with self MHC during development. Therefore having a setting where the addition of S. salivarius K12 activates NK cells, I investigated whether these NK cells were recruited to the draining lymph nodes where they could potentially influence the adaptive immune response. A range of adjuvant-activated and S. salivarius K12-activated DC were injected subcutaneously into the flanks of mice and tested their ability to recruit NK cells to the draining lymph node. The adjuvants differed markedly in their ability to recruit NK cells with S. salivarius K12 being the most effective. To determine if activated NK cells would be of benefit in tumour immunotherapy, I investigated the ability of bacterially activated DCs to elicit anti-tumour responses in a B16.OVA melanoma model. Utilizing a therapeutic tumour model where treatment was started three days following tumour inoculation, I found a significant delay of tumour growth in mice that were immunized with ovalbumin-pulsed DC that had been treated for 4 hours with S. salivarius K12 as opposed to other adjuvants tested. I also determined that in vivo depletion of NK cells completely abolished the benefit of DC immunotherapy. A therapeutic tumour experiment where DC were primed in the presence or absence of tumour antigen showed that while NK cells were critical for the antigen-dependent anti-tumour response they did not appear to exert an effector function. To investigate the role of NK cells in priming the anti-tumour response I next utilized a prophylactic setting, where mice were challenged with tumours sixty days after DC immunization. By depleting CD4+/CD8+ T cells and NK cells before time of priming or challenge, I tentatively showed that all three subsets of cells play a role in the anti-tumour response, although NK cells may play a greater role at time of challenge.

    View record details