University of Otago

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    Characterising the role of peroxidasin in breast cancer

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    The ability of cancer cells to migrate and invade into surrounding tissues is one of the fundamental hallmarks of cancer progression. The process of cancer cell invasion is not well understood leaving a gap in knowledge of potential cancer therapies. Peroxidasin, a peroxidase enzyme secreted to the extracellular matrix, has been found to be upregulated in numerous types of cancers. High expression of peroxidasin has been linked to a more invasive phenotype within melanoma cancer cell lines and our research project aimed to investigate whether this is also the case within breast cancer cell lines. We also investigated whether the modulation of peroxidasin activity and protein expression, using a peroxidasin inhibitor and short interfering RNAs, respectively, affects the ability of breast cancer cells to migrate and invade. Three breast cancer cell lines representing the different genetically distinct hormone receptor subtypes were chosen, namely the triple negative MDA-MB-231, the hormone receptor positive MCF-7 and the HER2 positive SKBR-3 cell line. Data analysis of peroxidasin expression in a breast cancer patient cohort from The Cancer Genome Atlas showed increased levels of peroxidasin in triple negative and human epidermal growth factor 2 amplified breast cancers compared to estrogen receptor positive. We determined peroxidasin protein expression and established that MDA-MB-231 expressed the highest levels of peroxidasin using a peroxidasin specific ELISA assay and Western blotting. These results are in line with the cancer cohort analysis. MDA-MB-231 also showed the highest migratory and invasive ability of the three cells lines in both 2D and 3D migration and invasion assays, corroborating our hypothesis of high expression of peroxidasin being connected to high invasive ability. Inhibition of the catalytic activity of peroxidasin using an inhibitor showed no effect on 2D migration, but showed reduced invasion in the 3D invasion assay in all three of the cell lines. The effect of short interfering RNAs, which resulted in reduced peroxidasin protein expression, was also investigated and showed a trend of reduced invasiveness for MDA-MB-231. Our results confirmed high peroxidasin expression in the breast cancer cell line with the highest invasive potential. Modulation of peroxidasin did show a slight decrease in the invasiveness of the cell lines but this needs to be further explored to determine significance. Our results showed that peroxidasin levels may be indicative of breast cancer invasiveness and may therefore be exploited as a diagnostic, prognostic or therapeutic tool and warrants further investigation

    Every move matters: Residential mobility and health and wellbeing outcomes in New Zealand children

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    Moving to a new house is common in childhood, particularly in New Zealand (NZ) where residential mobility rates are among the highest in the world. However, evidence regarding the prevalence of residential mobility and the implications of moving during early childhood is limited and little is known for NZ children specifically. This thesis addressed research questions about the prevalence of residential mobility and associations with health and wellbeing outcomes among NZ children using data from the Integrated Data Infrastructure (IDI). A systematic literature review and narrative synthesis (thematic analysis) of research on childhood outcomes associated with residential mobility was undertaken. To identify possible differential patterns among findings, five themes were identified: learning and academic achievement; internalising and externalising behaviours; health risk and problem behaviours; mental health, wellbeing, and relationships; and, physical health and access to services. Findings among studies on residential mobility in young children were mixed, although associations between residential mobility and adverse outcomes were mainly reported. A conceptual framework drawn from the literature review and synthesis and developmental and social capital theory was developed, illustrating the hypothesised links between residential mobility and health and wellbeing outcomes. Next, three retrospective cohort studies were conducted using a population-based child cohort drawn from the IDI linked administrative dataset. The main cohort comprised more than 300,000 children born since 2004, who appeared in the Before School Check database, a multi-component health and development screen universally administered to four-year-old NZ children. This includes the Strengths and Difficulties Questionnaire, a measure of children’s socioemotional and behavioural wellbeing. In Study 1, regression analyses showed residential mobility was associated with increased socioemotional and behavioural difficulties at four years of age (adjusted β = 0.16). Importantly, this association was linear, with each additional move associated with an increase in socioemotional and behavioural difficulties. In Study 2, residential mobility at two years of age was associated with increased risks for adverse health outcomes, including all-cause hospitalisations (aRR = 1.09), between two and four years of age. Lastly, in Study 3, residential mobility at four years of age was associated with a greater likelihood of school interventions (aRR = 1.06), adverse health outcomes including all-cause hospitalisations (aRR = 1.05), and grommet/aspiration procedures (aRR = 1.11) at eight years of age, and incomplete immunisation status (aOR = 0.96) at five years of age. Analyses with only Māori children from the cohort revealed a similar pattern of findings, although with slightly lower effect size estimates. Policy and practice implications of these findings are discussed in the context of health equity and housing stability, particularly for children from low-income households and those living in rental housing. Avenues for future research are suggested, emphasising longitudinal studies, residential mobility in the context of other housing characteristics, identifying groups of children for whom residential mobility is likely to have the most impact, and seeking greater understanding of children’s perspectives of residential mobility. Overall, this thesis provides population-level evidence that residential mobility in early childhood is consistently associated with small adverse effects across a range of health and wellbeing outcomes among NZ children

    The Coloniality of Whiteness: Countering Narratives of Oppression within 'Wai262 Ko Aotearoa Tēneiʼ

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    In 2010, in what has been described as "one of the most complex and far-reaching claims ever to come before the New Zealand Waitangi Tribunal”, a report concerning the theft of cultural and intellectual property rights relating to tangata whenua Māori (indigenous peoples of the land) by the Crown was released. ʻKo Aotearoa Tēneiʼ: (This is Aotearoa or This is New Zealand) or Wai262 as it is known, arose from findings of claims lodged in 1991 by claimants representative of six different iwi. Claimants sought to address the ʻownership and control of Māori culture and identity; the relationships that culture and identity derive from; and the role of the Crown in exercising ownership and control ". Examining the work and policy areas of more than twenty Government departments and State-Owned Enterprises as agents of the Crown, Wai262 provides an unsurpassed document to gain insight into how institutionalised State power establishes itself in order to retain authority, identity and control. Moreover, how that power is then enacted as a structure, as a language, and is therefore identifiable within narratives and text as a system of strategic, racialised domination and oppression synonymous with critiques of Critical Whiteness Theory. This Masters Research study examines how theoretical frameworks of Whiteness studies underpinned by Content Analysis methodology, can enable critical interpretations of Wai262 to further question the systematisation of politicized ʻpartnershipʼ, ownership and control; the relationship between Settler Colonial power and State domination in the role of the loss of mātauranga Māori; and counter oppressive colonial narratives that are embedded throughout the report. Keywords: Settler Colonialism, Colonial Violence, Whiteness, Colonial Enunciation, Historic Intergenerational Trauma, Counter Narrative, Content Analysi

    Inter-annual and inter-colony variation in the foraging environments and behaviour of tawaki from Milford Sound

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    As climate change intensifies, warming ocean temperatures, extreme weather events, and perturbations to the marine biome are becoming increasingly prevalent. A consequence of these changes are shifts in prey availability which can offset marine food webs and alter the foraging behaviours of marine predators. Seabirds are especially affected by alterations to the marine environment during the breeding season, when they are spatially constrained by the need to return to their colony and provision chicks. Thus, it is essential that their foraging habitats are productive and provide suitable conditions and prey stocks for successful foraging while minimising the energy expenditure required to locate and consume prey. To conserve seabirds in the face of significant changes to their ecosystem, it is necessary to develop a strong knowledge base of their habitat use and the degree of plasticity in their foraging behaviours. The Fiordland crested penguin (Eudyptes pachyrhynchus), also known by the Maori name of tawaki, are distributed throughout New Zealand’s southwestern coast and southern islands. However, little is known about the marine ecology of tawaki breeding within fiords even though fiordic systems cover a significant proportion of their range. Recent research has suggested that Milford Sound is able to buffer fiord-based tawaki from the usually detrimental effects of an El Niño year and provide them with favourable foraging conditions during their breeding season. This study presents the first comparison of guard stage foraging behaviour between two tawaki colonies from different locations within Milford Sound. Through the attachment of GPS/dive data loggers, dive parameters and spatial use were examined to determine differences in the foraging strategies of the inner-fiord colony (Harrison Cove) and the outer-fiord colony (Moraine) over the years of 2019 and 2020. Outer-fiord birds from Moraine foraged almost exclusively outside the fiord in both years while inner-fiord birds from Harrison Cove primarily foraged within the fiord in 2020 but not in 2019. Tawaki from Harrison Cove and Moraine also displayed contrasting dive behaviour across years, either adopting a strategy of deeper, longer dives with fast velocities or shallower, shorter dives with slower velocities. Foraging efficiencies for both colonies appeared to be greater in the year 2020 than 2019 although birds foraged differently to achieve this - Harrison Cove birds dived primarily to depths of 0-20m while Moraine birds switched between shallower dives at this depth and longer dives in the deeper 60-120m of the water column. Moraine birds adopted alternative foraging strategies across the years, with 2019 birds expending more energy on longer trips but diving shallowly while 2020 birds made shorter trips closer to their colony but exhibited higher foraging effort by diving deeply. Changes in dive behaviour across years were likely due to contrasting oceanographic factors affecting prey availability while differences between colonies reflect their differential foraging habitats. Environmental models revealed that ocean-foraging tawaki engaged in higher foraging activity and made deeper dives with faster descent velocities over warmer water and their dive behaviour was also influenced by salinity, concentrations of chlorophyll-a and seafloor bathymetry. Although the Oceanic Niño Index proved too coarse of a measure to assess changes in foraging patterns across years, local conditions in the fiord such as the interactive effects of salinity, rainfall and wind speed, were found to impact the dive behaviour of fiord-foraging tawaki. Rainfall, salinity and wind speed are all factors that contribute to the thickness and degree of mixing in the low salinity layer (LSL). A thicker LSL, as indicated by low salinity in the upper fiord waters, increased foraging activity and caused tawaki to dive deeper, exhibiting how the lower light environment caused by a thicker LSL does not necessarily compromise the foraging of tawaki. These findings highlight the considerable plasticity that tawaki possess in their foraging behaviours – they can forage in a range of environments and adapt their dive behaviour to fit the conditions. This bodes well for their future survival in an uncertain climate. Furthermore, this study emphasises the importance of not assuming that the foraging strategy of one colony is consistent with that of another nearby colony. Being situated in the inner fiord and within a marine reserve, has clearly influenced the foraging preferences of the Harrison Cove colony and it remains to be seen whether birds from the Moraine colony are capable of modifying their behaviour to make use of the fiord foraging habitat in years of harsh oceanic conditions and low productivity. The behaviour of tawaki across the rest of New Zealand’s fiord systems should be investigated in future to further understand the foraging opportunities fiords can provide and the significance of fiords in the conservation of this species

    Partner-centered interpretation in Aotearoa New Zealand: A hermeneutic for Paakehaa in partnership with Maaori

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    In recognition of the tino rangatiratanga of Maaori (the indigenous peoples of Aotearoa New Zealand) and the agreement to partnership by Maaori and Paakehaa (colonial settler New Zealanders of European descent) in Te Tiriti o Waitangi (Te Tiriti), this thesis proposes a partner-centred hermeneutical approach for biblical criticism in Aotearoa New Zealand. Since Paakehaa are legitimised in Aotearoa New Zealand through our relationship and partnership with Maaori in Te Tiriti, Paakehaa are relationally obligated to be in partnership and dialogue with tangata whenua (people of the land; indigenous people). This obligation means that to interpret the biblical text in Aotearoa New Zealand, partnership and dialogue with tangata whenua are essential. However, while some such interpretations have been previously attempted, the theory and method of partnership and dialogue with Maaori has not received much attention. This aspect of the discussion is crucial because we live in a context of systemic settler colonisation and racism. If Paakehaa attempt to interpret the biblical text in partnership and dialogue with tangata whenua without a theory that is attentive to this context, Paakehaa will inevitably recolonise the relationship under the guise of dialogue. This thesis builds on the philosophical hermeneutics of Hans-Georg Gadamer, the relational hermeneutics of Rev Prof Upolu Lumā Vaai, and the whakapapa hermeneutics in the Kaupapa Maaori discourse. Through these hermeneutical discussions, I argue that our partnership with Maaori in Te Tiriti is the foundation of our understanding of the biblical text in Aotearoa New Zealand. Paakehaa biblical criticism in Aotearoa New Zealand must arise from our partnered identity under the tino rangatiratanga (sovereignty) of Maaori. However, to do this, we (Paakehaa) must first recommit ourselves to the Tiriti Partnership with Maaori. I argue that this recommitment to Te Tiriti Partnership is characterised by: living relationship; relinquishing sovereignty, power, and resources; validation; responsibility; and support. By recommitting to Te Tiriti partnership, an equitable relationship of partnership becomes a possibility. I argue such an equitable relationship is a fundamental requirement for dialogue and understanding in interpretation. This partner-centred interpretive theory is then applied to 1 Corinthians 11:23–34 as a test case to explore whether a valid, partnership-based interpretation can be formed using this hermeneutic. This involves a three-stage method of interpretation. The first stage is re- perceiving the world through a metaphysical framework with our partner. The second stage analyses the text using the appropriate tools from “mainstream” biblical criticism. The final stage is to re-interpret the text through the co-constructed lens (developed in this first stage), thereby applying new questions and the co-constructed perspective to the text and suggesting a meaning of the text in this place. In analysing 1 Cor 11:23–34 using this hermeneutical approach and these methods, the passage, in which Paul addresses the abuses at the Lord’s Supper in Corinth, becomes laden with meaning for Maaori and Paakehaa in this place. The hermeneutic highlights the imperative for te Apo (the Greedy) in te haahi Koriniti (the Corinthian community) to return to tradition, move from self-interest to communalism, relinquish power, and restore relational equity and equality. Finally, I draw connections to the need of Paakehaa in biblical criticism to return to our partnership in Te Tiriti, stop seeking our own self-interest and, instead, seek the interest of our partner, relinquish the power we stole from tangata whenua through systemic settler colonisation, and ensure equitable funding and space for Maaori studentship and academics in biblical criticism which reflect the Tiriti partnership

    To what extent does a pharmacy curriculum foster diversity and inclusion through paper-based case scenarios?

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    Background: There is increasing awareness of diversity and inclusion needs within health and education systems to help address access and equity issues for minority groups. Although these calls are well known, there is little guidance for those working within these systems to create meaningful change. The purpose of this study was to critically review case-based teaching material within the authors' programmes through the lens of equity, diversity, and inclusion. Methods: A document analysis of clinical workshop cases extracted from all integrated therapeutics courses administered in 2020 was conducted. Results: Sex, age, and employment status were most commonly presented in cases (84.0%, 97.1%, 49.0% respectively). The majority (90.0%) of cases did not have ethnicity defined. The overwhelming majority of cases did not have living situation (68.3%) or sexual orientation (78.0%) defined. Conclusion: Case-based teaching material within a pharmacy programme was largely undefined according to patient demographics and diversity markers. Findings support the notion that teaching material may have a contributory role towards systemic racism, prejudice, and implicit bias.Peer Reviewe

    Feasibility of Monitoring Biochemical and Haemodynamic Effects of Angiotensin Converting Enzyme Inhibitors

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    Background Angiotensin converting enzyme (ACE) inhibitors reduce mortality and morbidity in heart failure, post-myocardial infarction and in those at high cardiovascular risk. However, recognised adverse effects contribute to hospital admissions. Aim To determine the feasibility of pharmacists collecting clinical data for ACE inhibitor prescribing and to inform the development of a hospital prescribing indicator set to measure the quality of monitoring for ACE inhibitors. Method A paper-based survey was conducted over 8 weeks. All patients admitted to a medical ward who were admitted on or started on ACE inhibitors were included. Data were collected prospectively and included serum creatinine, urea and potassium, and blood pressure measurements. These data were reviewed and compared against the parameter set for the indicator prepared. Results 29 patients were included in the analysis and cilazapril was most frequently prescribed (17, 57%). Blood pressure was recorded less frequently in new patients (7.7 vs 17.8). Creatinine was above normal on 47 (52%) occasions and 13 patients had an elevated level on at least one occasion. Creatinine was measured on average 3.1 times during the admission. Urea was measured for 15 (52%) patients, not measured for 14 patients and was measured for only one patient before prescribing an ACE inhibitor for the first time. Potassium was checked less frequently in new patients (average 2.5 vs 3.6 times per admission). Conclusion This study confirmed that it is possible for pharmacists to collect and collate clinical and prescribing data as part of a routine monitoring program for inclusion in a hospital prescribing indicator set. Data can be collected, analysed and reported back to clinical teams in a short time. The results suggest that inpatients receiving ACE inhibitors are adequately monitored for adverse biochemical effects

    Nematic spin vortices in spin-1 Bose-Einstein condensates

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    Spin-1 Bose-Einstein condensates present a wealth of physics, owing to the spin and superfluid order they possess. In this work, we consider spin-1 condensates with antiferromagnetic interactions, which favor the formation of spin-nematic order. Such condensates may exist in an easy-plane polar phase, and can support various topological defects with associated mass and spin currents. One defect of particular importance is the half-quantum vortex, which possesses both mass and spin circulation. The half-quantum vortex is equivalently realized in binary and easy-plane polar spin-1 condensates, and has been well-characterized theoretically, and observed in experiments. Another defect of interest is the nematic spin vortex, which possesses spin circulation, yet no mass circulation. The nematic spin vortex is thought to be unstable against decay into a pair of half quantum vortices. However, prior to this work, there was no general theory of nematic spin vortex stability. In this thesis, we develop formalism describing the structure and excitation spectra of axis-symmetric vortices in easy-plane polar spin-1 condensates. We apply this formalism to systematically investigate the structure and linear stability of nematic spin vortices in a uniform system, finding a parameter regime where they may exist as stable defects. We verify our stability predictions with dynamical simulations. Accurate numerical treatment of the stationary states and excitations of the nematic spin vortex in a uniform system has proved challenging due to the interplay of unstable and Nambu-Goldstone modes. Indeed, we found standard approaches to be ineffective. In this research we have developed new numerical schemes to resolve this issue, ultimately arriving at a robust approach able to provide sufficiently accurate results to illustrate the physics of the system. Investigation of our results should be possible in current experiments with sodium spin-1 condensates. Here the nematic spin vortices we describe could have implications for the non-equilibrium dynamics following phase transitions between magnetic phases. Furthermore, the numerical and analytic methods we have developed here will have immediate applications to other types of vortices in spin-1 condensates

    Consumer Acceptance of Novel Technologies Designed to Control Foodborne Bacteria in China and New Zealand

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    Foodborne bacteria, such as Listeria monocytogenes, are a heavy burden on human health and the world economy. To better protect consumers from foodborne bacteria while improving food quality, several novel technologies have been developed. The purpose of this study was to investigate Chinese and New Zealand consumers’ acceptance of novel technologies designed to control foodborne bacteria, as well as the effect of providing information on improving their acceptance, and the factors that might be able to influence their acceptance. An online survey was carried out, with 604 and 614 valid responses being collected in China and New Zealand, respectively. Respondents were asked to rate their acceptance of thermal pasteurisation (TP), high-pressure processing (HPP), irradiation (IR), bacteriophages (BP), antimicrobial packaging (AP), pulsed electric fields (PEF), and rinsing meat carcasses with antimicrobial solutions (RMCA) on three occasions and additional information was provided to respondents after their first and second ratings. After the first rating the material they were provided comprised of information about L. monocytogenes and a brief description of the technology, and after the second rating they were given information on the benefits of the technology. HPP was rated the most acceptable novel food technology in this study, which had the same acceptance as the traditional technology-TP- by the third rating. The acceptance of other novel food technologies was lower than that of TP to differing extents, with rinsing with antimicrobial solutions being rated as the least acceptable technology. In general, Chinese respondents showed a higher acceptance of the technologies. Information provided in this study influenced consumer acceptance of food technologies. Reading the benefits of a technology had a larger positive effect than reading information about L. monocytogenes and a brief description of the technology. In both countries, scientific reports and relevant national government agents were the most trusted information sources. The influence of a respondent’s knowledge and behaviours and their acceptance of technologies designed to control foodborne bacteria was investigated, including attitudes toward food technologies, awareness of foodborne bacteria, knowledge about L. monocytogenes, general food safety knowledge, food safety behaviour, food poisoning experience, and demographics. Consumer attitude toward food technologies and consumer awareness of foodborne bacteria were found to be major determinants for consumer acceptance of technologies designed to control foodborne bacteria. The findings from this research will expand the existing body of knowledge by determining the influence of a wider range of factors on consumer acceptance of food technologies and it will provide useful insights to help the food industry successfully develop, implement, and promote new food processing technologies to ensure food safety

    Development of hydrogel-based strategies for tissue vascularisation

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    The tissue engineering field and regenerative medicine has emerged as a promising strategy to overcome the lack of availability of organs and tissue grafts for transplantation. One of the main challenges in the field is to generate tissue analogues of relevant size with adequate nutrient and oxygen supply that promote graft integration and long-term functionality. The main strategies to promote tissue vascularisation are to either deliver bioactive cues such as growth factors (GFs), which attract the host vessels towards the area of interest, or to directly generate tissue analogues including a vessel network that can anastomose with the host blood vessels after implantation. This thesis aims to develop novel platforms to improve tissue vascularisation by delivering GFs and generating in vitro vascularised tissues. Firstly, a literature review summarises the main strategies to deliver GFs and to generate in vitro vascularised tissues, together with their present limitations for clinical translation. Next, a GF delivery system based on tyraminated poly(vinyl alcohol) (PVA-Tyr) is developed, which has the ability to covalently incorporate a range of native GFs and then release them in a controlled profile and during a tailorable time frame. The flexibility of this GF delivery system allowed its adaptation to the revascularisation of the femoral head in an in vivo model of avascular necrosis, which was done by adjusting the incorporated GF, the GF release time, the cell-material interactions of the system and its delivery method. This research is followed by the development of a gelatin-norbornene (Gel-NOR) platform that allows biofabrication of large vascularised tissues. The fabricated tissues combined a controllable pore structure, which mimicked larger vessels in native tissues, with encapsulated endothelial cells that were able to assemble into micro-capillary structures, mimicking the capillary beds in native tissues. These fabricated tissues were used as a model to study how design parameters can affect the behaviour of endothelial cells, demonstrating that pore diameter and fibre diameter could have an impact on the ability of endothelial cells to form micro-capillaries. Finally, the developed platforms were combined using bioassembly, which allowed understanding how different cell arrangements can affect endothelial cell behaviour within fabricated scaffolds and to develop tissue analogues that combine GF delivery with pre-vascularisation techniques. Overall, this thesis combines materials chemistry and design with advanced fabrication techniques to develop new strategies that address current limitations in the field of tissue vascularisation

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