1,299 results for Thesis, 2016

  • The chemistry of the bioluminescence of the New Zealand Glow-Worm

    Watkins, Oliver (2016)

    Doctoral thesis
    University of Otago

    The aim of the research described in this thesis was to discover the luciferin responsible for bioluminescence in the New Zealand glow-worm (GW) Arachnocampa luminosa. This work was done in partnership with Dr Miriam Sharpe whose focus was to elucidate the luciferase. In order to determine the structure of the GW luciferin, the luciferin had to be isolated from the GW and the structure elucidated via characterisation. However, luciferin purifications pose a unique isolation challenge, combining the difficulties of isolating material from source organisms, working with unstable materials, and working with enzymatic assays. Furthermore characterisation of luciferins is often difficult due to the small amounts that can be isolated and because luciferins are often highly unstable. Previous work on luciferins in other organisms and on the GW luciferin is reveiwed in Chapter 1. Chapter 1 also reviews the general literature on bioluminescence but with a focus on luciferins rather than luciferases. Chapters 2 describes the collection of Arachnocampa luminosa from the wild, and the development of a GW bioluminescence assay that enabled GW luminescent molecules to be detected. This assay enabled the detection of two different types of luminescence: P type luminescence and L type luminescence. Chapter 3 describes the separation of glow-worm lysates by reverse phase chromatography and how the luminescence assay was used to trace GW luminescent molecules through the purification process. This led to the discovery of two glow-worm luciferin precursors: tyrosine and xanthurenic acid that gave P type luminescence with the GW bioluminescence assay. The compound responsible for the L type luminescence was separated away from the compounds responsible for P type luminescence but could not be isolated. The compound responsible for L type luminescence was found to co-elute with tryptophan and is thought to be the GW luciferin. Chapter 4 describes how commercial samples of these precursors (xanthurenic acid and tyrosine), along with GW enzymes, were used to produce a compound (LRPA) that could be characterised by MS and 1H NMR. A solution of LRPA was found to produce L type luminescence with the luminescence assay showing LRPA to be either the GW luciferin or a closely related compound. Chapter 5 then describes the synthesis of two molecules (N-carbamyl tyrosine and phenol-O-carbamyl tyrosine) that were candidates for a compound that co-eluted with tyrosine. Neither of these molecules matched the unknown candidate which was later found to be 3-OH kynurenine. The research on the New Zealand glow-worm described in this thesis required intensive use of LC-MS techniques. However the research was often slowed by a shortage of glow-worms. These techniques were therefore used to investigate another New Zealand natural products problem involving insect metabolites; the origins of tutin, hyenanchin and the tutin glucosides found in New Zealand toxic honeys. Chapter 6 therefore describes a quantitative LC-MS study that shows that these compounds are of plant, not insect origin and that tutu may use glycosylation to aid in tutu transport.

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  • Aroha Across the Pa: Whānau and the role of Kuia in the 21st century - a Māori perspective

    Ikkala, Shirley (2016)

    Masters thesis
    University of Otago

    He wāhine, he whenua e ngāro ai te tāngata “by women and land men are lost” Kuia held key roles such as whare Mātauranga (repositories of knowledge) within whānau, linking past with the present and it is these roles that were valued and protected within whānau, hapū and iwi. Kuia nurtured and protected these roles and were the kaitiaki (guardians) of whānau, hapū and iwi knowledge thus ensuring the well-being of whānau, hapū and iwi. Historically many of these traditions were passed down through waiata, haka, whakataukī, mōteatea and were the primary means of transferring knowledge, values and belief. However, these traditional means of transferring knowledge have evolved with the advancement of technology and moving into the 21st century. Kuia were and are the kaitiaki (guardians) of the maintenance and transference of history and knowledge for future generations

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  • The Numerical Initial Boundary Value Problem for the Generalised Conformal Field Equations in General Relativity

    Stevens, Christopher Zane (2016)

    Doctoral thesis
    University of Otago

    The purpose of this work is to develop for the first time a general framework for the Initial Boundary Value Problem (IBVP) of the Generalised Conformal Field Equations (GCFE). At present the only investigation toward obtaining such a framework was given in the mid 90's by Friedrich at an analytical level and is only valid for Anti-de Sitter space-time. There have so far been no numerical explorations into the validity of building such a framework. The GCFE system is derived in the space-spinor formalism and Newman and Penrose's eth-calculus is imposed to obtain proper spin-weighted equations. These are then rigorously tested both analytically and numerically to confirm their correctness. The global structure of the Schwarzschild, Schwarzschild-de Sitter and Schwarzschild-Anti-de Sitter space-times are numerically reproduced from an IVP and for the first time, numerical simulations that incorporate both the singularity and the conformal boundary are presented. A framework for the IBVP is then given, where the boundaries are chosen as arbitrary time-like conformal geodesics and where the constraints propagate on (at least) the numerical level. The full generality of the framework is verified numerically for gravitational perturbations of Minkowski and Schwarzschild space-times. A spin-frame adapted to the geometry of future null infinity is developed and the expressions for the Bondi-mass and the Bondi-time given by Penrose and Rindler are generalised. The Bondi-mass is found to equate to the Schwarzschild-mass for the standard Schwarzschild space-time and the famous Bondi-Sachs mass loss is reproduced for the gravitationally perturbed case.

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  • What Happened at the End of Lapita: Lapita to Post-Lapita Pottery Transition in West New Britain, Papua New Guinea

    Wu, Pei-hua (2016)

    Doctoral thesis
    University of Otago

    This study presents a detailed Lapita to Post-Lapita sequence/transition with chronology at particular sites in west New Britain, through the medium of pottery analysis of style and production. The data allow me to address the research questions: (1) the cultural change that happened toward the end of Lapita, and (2) the issue of cultural continuity/discontinuity between the Lapita and Post-Lapita periods. This study identified a cultural change with greater break down and regionalization/diversification of the Lapita societies in the Late Lapita phase around and after 2750/2700 BP. This study also identified detailed pottery characterization, production, and provenance in west New Britain through compositional analysis, using a scanning electron microscope (SEM), which helps in understanding the interactions in the Lapita and Post-Lapita periods between west New Britain and other regions. In addition, this study identified a distinctive vessel form of double spouted pots of Lapita pottery that might originate from Island Southeast Asia, and demonstrates that after Lapita peoples had reached the Bismarcks, they maintained contact with homeland communities in Island Southeast Asia, and the double spouted pots were later introduced to the Bismarcks through interactions.

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  • Motherhood and Family Law

    Mackenzie, Fiona Amy (2016)

    Doctoral thesis
    University of Otago

    Throughout the broad sweep of history and related disciplines, including the law, can be found instruction with respect to the issue of motherhood. In one sense, it transcends culture; in another, it is a cultural construct. It is imbued with gender specificity and is profoundly important to children. This thesis explores motherhood’s relationship with family law and seeks to illustrate how, through uneasy tensions over time, it may have been compromised in modern child care law in New Zealand. It discusses whether parenting law should continue to adopt a gender neutral approach or whether, in considering a child’s welfare and best interests, there may be a case for greater recognition and restoration of gendered parenting relationships and perhaps, therefore, a repeal of s4(3) of the Care of Children Act 2004.

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  • Does a ‘baby-led’ approach to complementary feeding alter the risk of choking and growth faltering in infants aged 0-12 months?

    Fangupo, Louise Joan (2016)

    Masters thesis
    University of Otago

    Background: Although baby-led approaches to complementary feeding such as Baby-Led Weaning (BLW) are growing in popularity, research exploring the safety and efficacy of these approaches is sparse. Concerns have also been expressed regarding the potential for BLW to increase the risk of choking, growth faltering and iron deficiency. The Baby-Led Introduction to SolidS (BLISS) randomised controlled trial investigated whether a form of BLW, modified to address these concerns, was a suitable way to introduce solids to infants. Aim: To investigate whether the BLISS approach to complementary feeding alters the risk of food-related choking and growth faltering among infants aged 0-12 months. Methods: Dunedin families (n=206) were randomly allocated to a Control or intervention (BLISS) group. Control families (n=101) received the standard government funded ‘Well Child’ health service. BLISS families (n=105) received Well Child care plus at least 8 parent contacts for advice and support on following the BLISS approach. Data on the frequency of choking and gagging, the characteristics of choking events, and the impact of adherence to a baby-led approach to infant feeding were collected by questionnaires when infants were 6, 7, 8, 9 and 12 months of age. Choking and gagging frequencies were also assessed by daily calendars at 6 and 8 months. Data on infant exposure to foods thought to pose a choking risk were obtained using three-day weighed diet records at 7 and 12 months. Parental feeding practices were evaluated by questionnaires at 7, 8, 9 and 12 months. Infant growth was determined from repeated anthropometric measurements (infant weight at 6, 7, 8, 9 and 12 months, and length at 6 and 12 months). Growth was checked against five “growth triggers” to ensure the early identification of infants at potential risk. Growth faltering was defined as a weight deceleration of >1.34 of a weight-for-age z-score (using the World Health Organization Child Growth Standards) between 6 and 9 months. Results: Overall, 35% of infants choked at least once between 6 and 8 months of age but there were no significant group differences in the number of choking events at any time point (all p>0.20). BLISS infants gagged more frequently than Controls at 6 months (RR 1.56, 95% CI 1.13 to 2.17), but less frequently than Controls at 8 months (RR 0.60, 95% CI 0.42 to 0.87). At 7 and 12 months of age, 52% and 94% of infants respectively were offered food thought to pose a choking risk during weighed diet recording, although no statistically significant group differences were observed at either age (all p>0.30). Consistently safe parental feeding practices were often lacking in both groups, particularly at 12 months when only 44% of Control and 65% of BLISS infants always had an adult sitting with them while they ate. Although 32 infants (16 Control, 16 BLISS) met at least one growth trigger between 6 and 12 months, only 3 (2 BLISS, 1 Control) were potentially serious enough to be referred to the study paediatrician. However, growth improved in all three infants and no child met the criterion for growth faltering. Conclusions: Infants following the BLISS approach to complementary feeding were no more likely to choke or experience growth faltering than Control infants, although it is acknowledged that this was a relatively small study.

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  • Lapita Plants, People and Pigs

    Tromp, Monica (2016)

    Doctoral thesis
    University of Otago

    The Lapita cultural complex is associated with the Austronesian expansion out of Island Southeast Asia beginning approximately 3,500 BP. Sites associated with this archaeological culture have been found from the coast of New Guinea in Near Oceania and out past the Solomon Islands into Remote Oceania as far south as New Caledonia and as far east as Samoa by 2,700 BP. Major components of this culture include the commensal animals and horticultural plants that were transported with them as a portable subsistence economy during their voyaging. The commensal animal component of this package is reasonably well established, but the plant portion is less clear. This is primarily due to the scarcity of plant macro remains that have been found from archaeological sites and the lack of specificity of actual foods consumed in stable isotope analyses of archaeological human and animal bone. One direct way to explore the dietary plant component is to identify micro particles of plants (microfossils) that have been trapped within calcified plaque (dental calculus). The primary aim of this thesis is to examine the relationship between Lapita and immediately post-Lapita people and plants. The secondary aim is to examine whether human and commensal pig plant diets are similar and if it is possible to use pig diet as a proxy for human diet when human remains are not available for analysis. To address these aims, microfossils were extracted from human and pig dental calculus from four different sites: the SAC site on Watom Island, East New Britain Province, Papua New Guinea; Teouma on Efate Island, and Vao and Uripiv islands off the coast of northeast Malakula in Vanuatu. The samples were examined using a combination of light microscopy and scanning electron microscopy. All of the samples analysed date between Lapita (~3000 cal BP) and post-Lapita (~2500 cal BP) periods. These sites allow for a comparison of 1) an initial colonizing population (Teouma) and later populations (Watom, Uripiv and Vao), 2) Near Oceanic (Watom) and Remote Oceanic (Teouma, Uripiv and Vao) sites and 3) the wild versus cultivated plant components of their diets. The results show a much more diverse plant diet than has previously been shown. The importance of indigenous trees and shrubs to both Lapita and post-Lapita people analysed from all sites has been demonstrated in this study. Novel results include the first instance of banana seed phytoliths outside of the Bismarck Archipelago and an early introduction of Dioscorea esculenta to Vanuatu. The appearance of these non-indigenous plants at Teouma provides support for the concept of a “transported landscape”. However, the majority of identified plants were indigenous tree crops that suggest Lapita colonists were at least partly reliant on the forest resources that already existed on the islands they inhabited. This study represents the first direct plant evidence for Lapita and immediately post-Lapita diet of humans and pigs from this region.

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  • Assessing Learning, Breathing and Treatment of Respiratory Obstruction During Sleep in School Children: The ALBATROSS Study

    Maessen, Sarah Elizabeth (2016)

    Doctoral thesis
    University of Otago

    Introduction: Children with enlarged tonsils and/or adenoids are at risk for sleep disordered breathing (SDB), a common disorder in childhood characterised by snoring, choking, and pauses in breathing during sleep. SDB has been associated with a number of adverse effects on aspects of daytime functioning, including quality of life, behaviour, general cognitive functioning and memory. It has been documented that these difficulties can have a negative effect on school performance, but it is not known how children with SDB may differ from day to day in their school performance, or how their academic growth from week to week may be different from children without SDB. Furthermore, treatment of SDB by removing obstructive tonsillar and adenoid tissues can result in improvements in SDB symptoms, quality of life, and behaviour, but it is unclear whether this extends to school achievement. Previous research has used measures of academic performance such as parent and teacher report or standardised achievement tests. These kinds of measurements are not able to provide information about growth in academic achievement, and are not designed to be sensitive to treatment effects. The current research is a case series examining children on the waiting list for adenotonsillectomy (AT), a high risk group for SDB, using a multimethod-multi-informant approach to assessment. These children were assessed in domains where changes have previously been demonstrated after AT, i.e., SDB symptoms, quality of life and behaviour, as well as in academic performance, where results of previous research have been more equivocal. Methods previously used in SDB research to assess academic performance were used alongside alternative indicators of progress in literacy and numeracy. These measures were informed by evidence-based measurement approaches used to evaluate academic intervention, and were selected to probe skills specific to each child’s school year. This approach has previously demonstrated sensitivity to treatment effects in interventions for neurodevelopmental disorders. Methods: 20 case children aged 3-11 years were recruited from the waiting list for adenotonsillectomy at Dunedin Public Hospital. 19 of these children were matched to controls for age, sex, and school year, including academic performance where possible. 44% of participants were male, and 46% were preschool aged. All children were described in terms of their symptoms of SDB using parent ratings on the Pediatric Sleep Questionnaire, quality of life using the OSA-18 and Pediatric Quality of Life Inventory, behaviour using the SWAN rating scale and BASC-2 BESS , general cognition using the WPPSI-III and WISC-IV, and academic performance at matched time points both before surgery and at a follow up 7 months after surgery. In addition, an AHI was derived from home-based sleep studies conducted both before surgery and at a 3 month follow up. Academic performance was measured using parent and teacher judgements in relation to National Standards, performance on a standardised achievement test (WIAT-II Australian), and using the developmentally appropriate literacy and numeracy measures that were expected to be sensitive to changes across the study. The literacy and numeracy indicators were administered twice, one week apart, at each time point: twice before surgery (pre-‘surgery’), twice at the 3 month follow up (post-‘surgery’), and twice again at the 7 month follow up. These assessment points are similar to the timeline of previous SDB research. The current research takes both visual and statistical approaches to data analysis, allowing for examination of individual case-control pairs and within-subjects changes as well as group-level statistics. Results: At pre-‘surgery’, case children on average had more parent-reported SDB symptoms than matched controls (p = .001). This pattern was confirmed by AHI from overnight sleep studies indicating that the majority of case participants had clinically significant levels of SDB. As well as increased SDB symptoms, case children on average had poorer quality of life (range p = .001 - .032), behavioural and emotional functioning (p = .020), and memory (p = .001) than matched controls according to parent ratings. Teacher ratings did not suggest elevated levels of behavioural or emotional difficulties for either cases or controls and did not differ between groups, and mean general cognitive functioning scores were also similar between the groups. Typically used measures of academic performance, parent and teacher report and standardised achievement test scores, did not differ on average between case and control children, although case participants’ scores on the WIAT-II mathematics composite score were in the ‘low-average’ range compared to norms. Comparisons of literacy and numeracy indicators between the two pre-‘surgery’ sessions suggested that in general, case children appeared to have more consistent performance than controls from week-to-week, but less growth in these skills. When looking at mean performance on the tasks at pre-‘surgery’, several control children were outperforming their matched case participant, but there was a lot of individual variation in scores. After surgery, case children had improved parent ratings of SDB symptoms (p = .001), quality of life (range p = .001 - .023), behavioural and emotional functioning (p = .008), and memory (p = .014). With the exception of SDB symptoms and memory difficulties, which remained elevated for case children in comparison to matched controls, case and control children no longer differed statistically for mean scores in any other domain of daytime functioning. Teacher ratings of reading in relation to National Standards improved for case children (p = .011), but no other typically used measures of school performance changed notably following surgery. Improvements in scores on the literacy and numeracy indicators suggested different patterns of growth for different academic domains and age groups. For preschoolers, case children showed evidence of linear growth in an early literacy composite that was steeper than for control children on average (p = .008). However, improvement in early numeracy scores suggesting growth in these skills did not differ between case and control participants on average. Year 1 and 2 case participants showed considerable growth in a phoneme segmentation fluency task that was not observed for their matched controls, but there were no clear patterns for any other literacy or numeracy tasks. Children in Years 3 to 5 had improvements in literacy tasks that for some participants were greater than their matched controls, but did not appear to improve in numeracy. Year 6 and 7 students, in contrast, demonstrated evidence of growth in numeracy tasks, but most did not improve in literacy tasks. Conclusions: This research is consistent with previous studies reporting that children with SDB are at risk for poor academic performance or growth. The literacy and numeracy indicators used in the current research provided information about academic performance in these children beyond what could be ascertained from more conventionally used measures. This finding suggests that these more sensitive measures of academic growth have potential for evaluating effects of SDB treatment on academic performance in a larger group of children. The current study has clearly demonstrated that children who are undergoing surgery for removal of tonsils and adenoids in Dunedin are likely to have more symptoms of SDB and related negative effects on daytime functioning when compared to similar children in the community. It also provides preliminary evidence that treatment of SDB in early childhood may help to improve learning trajectories in literacy skills, supporting existing evidence for early identification and intervention for SDB. Many children are affected by health problems other than SDB or behavioural difficulties that have been associated with poorer school performance. The literacy and numeracy indicators used in the current research show promise for assessing the effects of surgical intervention for SDB, and therefore have the potential to explore the effects that treatment of other disorders that can affect school performance, such as otitis media (glue ear) or ADHD, could have on academic achievement.

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  • He Kiteka Hauā i Murihiku. Perspectives of disability and wellness of hauā Māori living in Murihiku

    Bryant, Katrina Anne Pōtiki (2016)

    Masters thesis
    University of Otago

    Disability is of considerable concern for Māori as they are over represented in this area and have more severe disabilities than the non-Māori population in Aotearoa/New Zealand. Whilst many initiatives have been put forward to facilitate access to disability services, utilisation of services remains proportionately low for hauā Māori (Māori living with disability) despite their experiencing a higher incidence of multiple disabilities. This poor uptake of services indicates the need for targeted research to assess Māori experiences and viewpoints of disability, in order to better understand how to deliver relevant services for hauā Māori and their whānau (families). Given the prevalence of disability within the Māori population, it is also interesting to note the concept of ‘disability’ is largely non-existent within Te Ao Māori (Māori world-views) and in recent literature. Investigating the impact of disability for Māori and their whānau, more specifically Māori perceptions of ‘disability’ (MOH, 2011), has been identified as a research priority by Māori whānau living with disability. In 2012, a collaborative study, Hauā Mana Māori, was conducted to explore, accessibility issues for hauā Māori and their whānau. This thesis reviews the qualitative component within this project that explicitly explored hauā Māori perspectives of disability and health and also aims to present the effective data collection techniques developed to perform disability research within this community. This study was guided by Kaupapa Māori Research (KMR) methodology, using philosophies steeped in tikaka Māori (Māori culture), Whānau Ora (community well-being) and hauora Māori (Māori health) ideologies. This process was largely informed by a group of hauā Māori living in Murihiku, Rōpū Kaiārahi (leadership group), to ensure the methods used were relevant and empowering to hauā Māori. Thirty hauā Māori living in Southern Aotearoa/New Zealand were interviewed using the data collection instrument, the Whakāro Pōkare Visual Tool, and the findings from thematic analysis are presented within. Common themes of wellness for hauā Māori interviewed included feeling valued, being connected to community, having a strong sense of self and self-worth, having access to determinants of health and having a positive approach towards physical health. Conversely, frequently referred to themes within perspectives of disability comprised of being undervalued, feeling disconnected, a low self-esteem, limited access to resources and poor physical health. A noteworthy finding was that many hauā Māori do not consider a physical limitation a disability, and are therefore not whakamā (embarrassed) to openly discuss issues that non-Māori tend to avoid. This attitude revealed a cultural dissonance, between Māori and non-Māori views on disability and pointed to a preference of Māori perspectives of acceptance for the hauā Māori interviewed. Lastly, being guided by KMR principles allowed for relevant research process to be established leading to the development of an appropriate qualitative data collection instrument, the Whakāro Pōkare Visual Tool. This tool enabled the qualitative research to successfully collect voices of hauā Māori. Participants reported beneficial outcomes from being interviewed using the data collection tool. Future research investigating the potential for utilisation within the clinical setting is suggested.

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  • 24 – hour oxygen saturation recordings at discharge in preterm infants

    Wellington, Grace Charlotte (2016)

    Undergraduate thesis
    University of Otago

    Preterm infants have an immature respiratory system and therefore experience an increased number of respiratory pauses and oxygen desaturations. There is now advanced pulse oximetry technology that can record oxygen saturations every two seconds for extended periods of time. There has been insufficient literature that reports the incidence of intermittent hypoxia at time of discharge home from the neonatal unit in preterm infants using new generation oximeters. These respiratory events preterm infants experience have been shown to have some effect on neurodevelopment, but their effect on growth has not been investigated before. The primary aim of this study was to determine the prevalence of intermittent hypoxia in preterm infants at time of discharge home from the neonatal unit. The study also addresses the issue of artefact within oximetry recordings and compares results from automatically edited, manually edited and unedited oximetry data, as well as determining whether overnight 12-hour recordings are of equal value to full 24-hour recordings. The secondary aim of this study was to determine whether intermittent hypoxia at discharge has any effect on post discharge growth and to determine changes in amount of intermittent hypoxia from discharge oximetry to oximetry one-month post discharge. We recruited preterm infants from the Wellington neonatal intensive care unit. A 24-hour pulse oximetry recording was performed immediately prior to the infant’s discharge home. These oximetry recordings were analysed and median values for measures reported from oximetry recordings were determined. Rules to manually edit oximetry data were created and applied to oximetry recordings. These manually edited reports were then compared with automatically edited and unedited reports. Each recording was also edited to resemble a 12-hour overnight recording and this was compared to the full 24-hour recording. Infants born less than 32 weeks gestational age were further followed up with weekly growth measurements for one-month. A repeat 24-hour oximetry recording was performed at one-month post discharge for these infants and compared to their discharge recording. We report high rates of intermittent hypoxia in preterm infants at time of discharge home from the neonatal unit. For example the median 4% oxygen desaturation index (DSI 4%). was 57.9 events per hour. The incidence of these events decreased with advancing post-menstrual age. Rates of intermittent hypoxia one month post discharge were greatly decreased from discharge with improvements of 42% - 57% seen, with DSI 4% reducing to 25.5 events per hour. This study did not show a significant association between intermittent hypoxia and post-discharge growth, possibly because of the small sample size in this study subgroup. There were few clinically relevant differences on reports edited manually compared with automatically edited reports, with some difference when compared to unedited reports. We recommend automatically editing oximetry reports as this gives similar results to manual editing for the majority of measures, however the nadir of the fall in oxygen saturation is often artefact, and even after automatic editing is the one measure that may remain false. The 24-hour oximetry reports were clinically similar to 12-hour recordings and therefore we suggest 12-hour oximetry studies are sufficient.

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  • Managing Jurisdictional Overlap for Closed Coastal Landfills: An Evaluation of Cross-jurisdictional Planning Practice within New Zealand

    Lindsay, Kirstyn Jane (2016)

    Masters thesis
    University of Otago

    Cross-jurisdictional management is a complex and, at times, fraught issue and this is never more obvious than in the coastal environment. When closed landfills and associated contamination effects are also present within this environment, additional layers of management complexity are introduced. Effective management of these environments depends on support from the legislative framework and the capacity and willingness of those agencies responsible for each jurisdiction to facilitate a co-ordinated and integrated approach. The purpose of this research is to examine current approaches to cross-jurisdictional management to identify how planning practice may be improved. The research considers the theoretical framework surrounding integrated management and inter-agency co-operation and reviews current planning practice against the theoretical framework. It explores the nature of the organisations responsible for cross-jurisdictional management and how organisational structure, culture and communication empowers or hinders collaboration and inter-agency relationships. The research design includes a contemporary case study involving multi-agency management of a closed coastal landfill and interviews with planning practitioners practicing within New Zealand. The research found that while the legislation may not have been overtly encouraging of a co-operative management approach, it did not hinder or obstruct co-operation; rather any lack of co-ordination was more a consequence of inter-agency relationships. Communication between organisations was often inconsistent and perfunctory, and effective communication and relationship building did not appear to be prioritised. Ultimately, the research found that optimising inter-agency relationships and undertaking clear and frequent communication is fundamental for effective and efficient cross-jurisdictional management of closed landfills within the coastal environment.

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  • Understanding How Mature Students Make Sense of Success in the Social Work Programme at the University of Otago

    Roxborogh, Phillip Andrew (2016)

    Masters thesis
    University of Otago

    My thesis explores how mature students, those aged 25 or older, understand the knowledges necessary for success in the social work programme at the University of Otago. In this thesis I argue that there is a social logic that underpins the programme which sits below the awareness of all involved and acts to marginalise those who lack the knowledges privileged by that logic. In turn, I propose that when staff, mature and non-mature students, the university, and the social work profession make use of this information, they can foster an environment where student success is revolutionised. My vision is a programme where everyone is successful and no one is marginalised. As a starting point, I have included a table of contents of a student success guide for future discussion. The use of Pierre Bourdieu’s thinking tools allow this social logic to be revealed in all its complexity. As such, my study was conducted as a qualitative research endeavour, where the work of Bourdieu and Wacquant (1992) informed an analysis of the social work programme at a government, profession and programme level to reveal the social logic in operation. I then utilised an online survey combined with follow-up focus group and semi-structured interview events to determine how staff and students made sense of my findings for maximising student success. My thesis contributes to the debates on 1) using the work of Bourdieu to analyse the dynamics of power in an education context to bring to the surface the social logic of a field of interactions, 2) using that knowledge as a basis for bringing about the positive social transformation of those in marginalised positions by equipping struggling agents to play the social game better, and by changing the game itself to be more supportive of struggling, and, 3) how the transformation of the experience of struggling agents requires the enabling actions of those in positions of power.

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  • Postprandial glucose and insulin response to regular activity breaks in comparison to prolonged sitting: the effect of physical activity the previous day

    Homer, Ashleigh Rose (2016)

    Masters thesis
    University of Otago

    Sedentary behaviour has become a well-known risk factor for cardio-metabolic disease. Results from observational studies indicate that regularly breaking sedentary behaviour with light bouts of physical activity is associated with lower risk of cardio-metabolic disease. It has been proposed that breaking sedentary behaviours improves cardio-metabolic risk primarily through processes involved in postprandial metabolism, in particular attenuating the glucose and insulin response. Abnormal glucose and insulin metabolism in the postprandial period is a well-known indicator of cardio-metabolic diseases. Therefore, the aim of the current study was to investigate the effects of two days of prolonged sitting and regular activity breaks (2 minutes brisk walking every 30 minutes), with and without physical activity (30 minutes continuous brisk walking) at the end of the first day, on postprandial glucose and insulin metabolism on day two. A randomised crossover, laboratory based study was conducted in Dunedin, New Zealand between June 2014 and November 2015. Thirty-six healthy, normal weight adults (Mean (SD) BMI 23.8 (4.0)) aged 18 to 35 years participated in four interventions. The interventions were conducted over two consecutive days each, separated by at least 5 days and consisted of: 1) Prolonged Sitting, during which participants sat continuously for 7.5 h and 6 h on two days of clinic visits; 2) Physical Activity, during which participants remained seated for 7 h on Day 1, followed by a 30 minute continuous brisk walk, and remained seated for 6 h on Day 2; 3) Regular Activity Breaks, during which participants interrupted their sitting every 30 minutes with 2 minutes of brisk walking on a treadmill, performing a total of 14 walks on Day 1 (28 accumulated activity minutes) and 10 walks on Day 2 (20 accumulated activity minutes); 4) Regular Activity Breaks plus Physical Activity, during which participants interrupted their sitting every 30 minutes with 2 minutes of brisk walking on a treadmill for 7 h on Day 1, which was followed by a 30 minute continuous brisk walk, and Day 2 was completed identical to the Regular Activity Breaks intervention. Glucose and insulin metabolism was measured in response to a mixed meal fed to participants at 0 h on Day 2 consisting of 0.71 g.kg-1 carbohydrate, 0.70 g.kg-1 fat, 0.32 g.kg-1 protein and 43.24 kJ.kg energy. Blood samples were collected from a venous cannula at baseline and hourly for 5 h, with additional samples collected at 30 and 45 minutes after the meal was fed. Postprandial responses for plasma glucose and insulin were calculated as total area under the curve (tAUC). Postprandial glucose response was not significantly different between interventions. Postprandial insulin tAUC response decreased from 140.6 uU.mL-1.h during Prolonged Sitting to 125.6 uU.mL-1.h during Regular Activity Breaks (Ratio of Difference 0.89; 95% CI 0.80, 0.99; P = 0.037), 120.0 uU.mL-1.h during Physical Activity (Ratio of Difference 0.85; 95% CI 0.75, 0.96; P = 0.008), and 109.3 uU.mL-1.h during Regular Activity Breaks plus Physical Activity (Ratio of Difference 0.78; 95% CI 0.69, 0.88; P < 0.001). There was also a significant decrease in postprandial insulin response between Regular Activity Breaks interventions without (125.6 uU.mL-1.h) and with Physical Activity (109.3 uU.mL-1.h) i.e. Regular Activity Breaks plus Physical Activity (Ratio of Difference 0.87; 95% CI 0.79, 0.97; P = 0.008). The lack of effect of any of the interventions on glucose response is in contrast with previous studies, and may indicate a lack of sufficient glucose challenge provided to the sample of young, healthy adults. The combined Regular Activity Breaks plus Physical Activity intervention was the most effective (i.e. greatest reductions) at lowering postprandial insulin response in comparison to Prolonged Sitting. These findings indicate that over two days breaking prolonged sitting with short bouts of activity combined with a singular 30 minute bout of activity has sustained metabolic benefits on postprandial insulin response.

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  • The role of free clinics in primary health care for vulnerable people: Policy and theory development based on empirical analyses of the free clinic in Dunedin, New Zealand.

    Loh, Lik Wei (2016)

    Doctoral thesis
    University of Otago

    A clinic providing primary health care services free-of-charge to all its enrolled patients opened in January 2010 in Dunedin. It was staffed by volunteer clinicians, many of whom were motivated by their Christian faith. Its patients were socially vulnerable, and had complex health needs. This setting provided an opportunity for a ‘natural experiment’, whose aim was to study the delivery, context and effects of free primary health care, and the socio-demographic and clinical characteristics of the target population using such services. The expectation was that the removal of the cost barrier would enable vulnerable patients to better access comprehensive health care. Since capturing the phenomenon (free primary health care provision) and its context were fundamental to understanding the Free Clinic, the case study methodology was used to examine the application of the phenomenon, as part of developing theory around the place of free general practice care in New Zealand. This case study comprised four component studies. A questionnaire-based study compared the socio-demographic characteristics of patients at the Free Clinic and those at a nearby fee-charging traditional clinic. A nested case study examined the nature of Free Clinic patients' diverse needs, the Free Clinic's model of care, and whether the model was a good match to patients' needs. An audit of electronic records was performed to profile the reasons Free Clinic patients consulted their general practitioner. A controlled before-and-after study of Free Clinic patients matched to other Dunedin residents by propensity scores assessed the effect of the Free Clinic on hospital use by its patients. These studies combined qualitative and quantitative research methods. Free Clinic patients were on average younger and more likely to be Māori than the wider Dunedin population, and more likely to reside in highly deprived areas, and report high levels of individual-level deprivation. Despite their poorer self-reported health status and greater levels of multimorbidity, Free Clinic patients were likely to report having unmet needs for medical and dental services, and not being able to collect prescription items because of cost. When asked to comment on the Free Clinic’s model of care, patients placed value on the “friendly” and non-judgmental nature of the care they received, and being able to simply drop-in without an appointment to receive support for diverse health and social concerns. Free Clinic patients brought fewer than average ‘reasons-for-visit’, and tended to consult for administrative and repeat prescription requests. Follow-up of Free Clinic patients for five years after the clinic’s opening failed to reveal any significant decrease in their hospital use. Compared with matched controls, Free Clinic patients visited the emergency department more frequently after the clinic opened than before it opened. Beyond access to health care, patients such as those attending the Free Clinic need access to the social conditions and resources that promote health. Beyond a model of care sympathetic to their needs, a protracted period of making small, incremental efforts is necessary before gains in health may be reaped. Given the limitations of the current primary health care funding and service delivery framework, the establishment of designated ‘fit for purpose’ clinics for vulnerable populations is necessary. Further research is needed to identify primary health care patients with significant unmet health needs, and to find an appropriate measure other than hospital use to evaluate policy interventions aimed at improving primary health care access.

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  • An Analysis of the Extent, Purposes, and Outcomes of Ski Areas’ Environmental Communications

    Spector, Samuel (2016)

    Doctoral thesis
    University of Otago

    This qualitative study investigates the extent, purposes, and outcomes of environmental communications (hereafter ECs) produced by ski areas on New Zealand’s South Island. Researchers have examined why ski areas participate in environmental initiatives, but there is a dearth of knowledge regarding why communications about these environmental efforts are published. Skiing exerts significant environmental impacts but is simultaneously reliant on particular environmental conditions. The ECs of ski areas, as one way in which reactions to these impacts and vulnerabilities are communicated, warrant study. In addition to analysing the ski areas’ ECs, semi-structured, in-depth interviews with insiders from the ski areas and with skiers were used to investigate the extent, purposes, and outcomes of the ECs. Legitimacy theory, which postulates that organisations must demonstrate they embrace societal values in order to remain profitable, is utilised as a theoretical lens for approaching this topic. Thematic data analysis of the ECs, interviews with ski area managers, and interviews with skiers was conducted using an inductive, interpretive approach which allowed for the periodic revision of coding themes as they emerged throughout the analysis process. The following themes were identified from interviews with ski area insiders and analysis of the ski areas’ ECs: a focus on local, tangible environmental issues, numerous constraints restricting the production and dissemination of ECs, a range of impetuses driving engagement in EC, EC as interwoven with developing and maintaining social legitimacy, and the outcomes of EC being seen as distinctly varied. As predicted by the insiders, analysis of interviews with skiers found they were unaware of ECs not related to recycling; and, due to the perceived lack of prominence of the ECs, skiers did not express sentiments of ‘green fatigue.’ As also anticipated by the insiders, skiers were unwilling to make destination choices or restrict skiing based upon the ski areas’ environmental performance. Skiers believed the ECs are published because there is no disadvantage to doing so and a competitive advantage amongst a small audience may result, they accepted the accuracy and legitimacy of the ECs, and they perceived skiing to be a relatively benign use of nature. Follow-up interviews with ski area insiders allowed discussion of key points of interest from the interviews with skiers. During the follow-up interviews the insiders contrasted local skiers, ski area staff, and the Department of Conservation with ‘holiday skiers’ (the latter being seen as not prioritising environmental performance) to explain why ECs continue to be published despite skiers’ lack of awareness of those communications and unwillingness to make destination choices based on such factors. The insiders viewed skiers’ lack of ‘green fatigue’ as stemming from the ski areas’ restrained approach to using ECs, the small size of the ski areas, and the ‘clean and green’ image attached to New Zealand. In addition to the formal thematic analysis, two discussion points are critically examined. First, the thesis offers a critique of EC due to the complexities inherent in delineating the concept. These complexities arose both in terms of demarcating the ‘environmental’ aspect of EC (e.g. non-environmental factors, such as a ski area being family owned, being salient in shaping how the ski area’s environmental impact is viewed) in addition to the ‘communication’ aspect of the concept (e.g. communications arising from skiers rather than the ski area via dialogue-enabled mediums such as social media potentially influencing a ski area’s pro-environmental image). Second, there is a lack of attention afforded ski tourists’ transportation when envisioning an environmentally responsible skier or ski area. Interviews with ski area insiders indicated they view skiers’ non-local transport as outside their purview. Skiers likewise did not deem themselves or the ski areas as responsible for addressing transport-related impacts. As climate change poses one of the greatest threats to tourism in general, and skiing specifically, the lack of substantive efforts to address tourists’ transportation is egregious.

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  • How do New Zealand small to medium-sized (SME) fashion design firms acquire knowledge during the internationalisation process?

    Lowry, Brooke (2016)

    Masters thesis
    University of Otago

    The purpose of this research is to understand how New Zealand fashion small to medium-sized enterprises (SMEs) acquire knowledge during the internationalisation process. A qualitative case study of four firms has been used to explore this research question. The findings of this research suggest that New Zealand SME fashion design firms acquire different forms of knowledge and learning from various sources during the internationalisation process by serendipity and also by design, as will be discussed. This research contributes to the existing internationalisation literature by extending the Six Markets Model (Payne, Ballantyne & Christopher, 2005) from relationship marketing literature to illustrate how SMEs acquire knowledge during the internationalisation process, and from which sources. This study also identifies the forms of knowledge and sources of knowledge that SME fashion firms need if they are to internationalise successfully. A limitation of this research is that this study focused on the New Zealand fashion design industry alone. Therefore future research should focus on extending the application of the Six Markets Model on stakeholder relationships in other contexts, such as industries where SMEs comprise a significant proportion of the national economy.

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  • A Discourse Analysis of Self-management for Bipolar Disorder

    Wilson, Lynere Deborah (2016)

    Doctoral thesis
    University of Otago

    In line with a movement across all areas of health concerned with chronic illness, self-management practices have become an important part of what it means to provide contemporary mental health care to people with the psychiatric diagnosis of bipolar disorder. In mental health settings it is a taken-for-granted practice. The aim of this thesis is to use Foucauldian Discourse Analysis to explore how the discursive practices of self-management for bipolar disorder produce particular forms of subjectivity for those understood to have the condition and the implications of this for processes of self-formation. In order to consider how discourse is used to both govern others and govern the self, two sources of text are used for analysis. The first source is the Psychoeducation Manual for Bipolar Disorder (Colom & Vieta, 2006) which details how mental health professionals can teach people with bipolar disorder about their condition in order that they might better manage themselves. The questions guiding the analysis of this text as how discourse constructs bipolar as an object, what subject positions it makes available and what relationship people are expected to have with the object named as bipolar disorder. The second source of text are the transcripts of semi-structured interviews completed with 25 people with bipolar disorder as part of their entry to a clinical trial of psychotherapy and medication management as a means to reduce rates of acute psychiatric assessment and hospitalization. Analysis of these texts is concerned with how discourse is used to govern the self and is developed in a two stage process. The analysis is guided firstly by questions that ask how bipolar disorder is constructed, how is self-management constructed as an object, how is life with bipolar disorder constructed and what discourses are drawn on the process. The second stage of analysis of these texts focuses on the subject positions being made available in self-management discourse. This analysis finds that as an object, bipolar disorder is constructed as both an illness of the brain and an object the produces an unreliable mind such that it is an object that is separate from a person’s sense of self while also being an object that interferes with the mind’s capacity to know itself. This results in persistent tensions to be negotiated within self-management practices such that self-management discourse produces subject positions characterised by dividing practices and contradiction. The discourses of medicine and psychology can be seen to act to tightly regulate how bipolar disorder can be understood which results in all aspects of a person’s self being shaped by the condition they are understood have. These discourses have become the only way a person can legitimately construct a sense of themselves and through the workings of pastoral styles of power relationships psychological discourse can be seen to be used ultimately in the service of medical discourse. With self-management discourse seen as operating on the basis of division and contradiction, this thesis proposes that the nature of the problem in the self-management of bipolar disorder is not the disorder or the person it is understood to inhabit but rather the norms of the self on which contemporary Western society bases its understanding of what it means to be a normal subject. The thesis concludes firstly with two alternate constructions of selfhood; the self as formed through connection and the self as formed through the management of the abject and then with a proposal for an alternate approach to psychoeducation as a particular strategy of self-management discourse for bipolar disorder. The significance of this thesis lies in its use of a Foucauldian methodology to question the assumptions of beneficence understood to drive the promulgation of self-management practices in health care. Its resulting re-evaluation of the nature of the self in the discursive practices of self-management for bipolar disorder and its proposal for an alternate approach to psychoeducation is put forward as a contribution to the project of a contemporary critical psychiatry.

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  • Factors affecting glucose homeostasis in premature neonates

    Salis, Emma (2016)

    Doctoral thesis
    University of Otago

    Introduction After birth rapid metabolic adaptation is required to establish glucose homeostasis.Preterm birth disrupts normal timing of this physiological adaptation putting premature neonates at risk of hypo- and hyperglycaemia. A major barrier to conducting pharmacokinetic studies in neonates is the relatively large volume of blood required by most assays. The use of dried blood spots (DBS) has the potential to enable the use of smaller sample volumes and simplifies processing and handling. However, haematocrit in neonates varies significantly and can affect the accuracy of DBS assays. Insulin and C-peptide are secreted in equimolar amounts from the pancreas. C-peptide can be used as a biomarker for insulin secretion as, unlike insulin, it is not hepatically cleared and has a longer plasma half-life. Urinary C-peptide may give a non-invasive way of measuring insulin production in neonates. The insulin/C-peptide (I/CP) ratio gives an indication of relative insulin clearance in adults but normal ranges have not been reported in neonates. Premature neonates have significantly higher fasting levels of glucagon-like peptide-1 (GLP-1) than adults and are increased even further with feeding. Hyperglycaemia can often occur in extremely premature neonates and is associated with an increase in morbidity and mortality. Insulin resistance is a key issue in preterm neonates and it is thought that hyperglycaemia is a consequence of relative insulin deficiency. Aims The aims of this research were: to investigate the use of a DBS assay for measuring insulin concentrations to improve sampling for pharmacokinetic studies; to describe the relationship between C-peptide and insulin secretion in the neonatal population; to investigate the relationship between feeding, incretin (GLP-1) and insulin secretion in neonates. Finally, to compare these results with neonates treated with insulin for hyperglycaemia to investigate alterations in glucose homeostasis in hyperglycaemic neonates. Methods Blood samples, DBS and urine samples were obtained from euglycaemic and hyperglycaemic insulin-treated preterm neonates admitted into the Dunedin Hospital Neonatal Intensive Care Unit (NICU) for this research project. DBS of varying haematocrit (0.25-0.65) were prepared at three insulin plasma concentrations (10, 25 and 50mU/L) and were analysed for insulin using the method developed by Butter et al (2001). DBS and paired plasma samples were obtained from neonates. Standard addition and direct measurement from the kit standard curve were compared for measurement of urinary C-peptide. Insulin concentrations in plasma, along with C-peptide concentrations in plasma and urine (diluted to 40%) were measured in 20 neonates. Urine volume and time of collection were recorded and used to calculate C-peptide urinary excretion rate (UER) and clearance (Cl). Samples for 102 euglycaemic neonates were obtained from leftover blood from routine tests. Samples were obtained for 10 hyperglycaemic insulin-treated neonates and there were 9 for which additional blood was collected at the same time as the patients’ routine four hourly blood glucose test over a 24-hour period (6 samples). Data were collected from clinical notes for gestational age (GA), postmenstrual age (PMA), postnatal age, birth weight, current weight, birth length, birth head circumference, oral intake, and intravenous fluids at time of samples. Insulin and C-peptide concentrations from the hyperglycaemic insulin-treated neonates were compared with a group of age-matched (PMA 0.05). Direct measurement from kit standards produced a more precise and simple method for determining C-peptide concentration. The mean (SD) C-peptide Cl was 0.309 (0.329) mL/min/kg and UER was 0.0329 (0.0342) pmol/min/kg. Correlations between Cl or UER and gestational age were not significant (p >0.05). No significant correlation was shown between UER or Cl and blood glucose concentration (BGC). Insulin and C-peptide concentrations were elevated in very preterm infants (PMA ≤32 weeks) and decreased as the neonate approached term. Data were natural log normally distributed and linear regression of ln-transformed data was performed. Linear regressions showed that I/CP ratio and insulin/BGC (I/BGC) ratio decreased significantly with increasing PMA (p <32 weeks). C-peptide concentrations were significantly lower in the hyperglycaemic neonates indicating lower insulin production in hyperglycaemic neonates. Treatment with exogenous insulin did not suppress insulin production in these neonates.

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  • Effects of Ocean Acidification, Temperature and Copper on the development of early life stages of the Native Kelp Macrocystis Pyrifera and the Invasive Kelp Undaria Pinnatifida from Southern New Zealand

    Leal Sandoval, Pablo Patricio (2016)

    Doctoral thesis
    University of Otago

    Anthropogenic activities have increased atmospheric CO2 concentrations from pre-industrial concentrations of 280 ppm to current values of 400 ppm. These atmospheric emissions of CO2 are responsible for the ongoing increase in seawater temperature and the reduction of pH in the ocean’ surface, phenomena known as ocean warming (OW) and ocean acidification (OA), respectively. Model-based projections indicate that the global ocean surface temperature will increase by 4°C whereas the pH will decrease from a current 8.10 to 7.74 by 2100. However, these two global events are not occurring in isolation because anthropogenic activities also threatens coastal environments at local levels. For instance, in coastal environments, natural concentrations of copper are low but are increasing due to human industrialization. In addition, the speciation and bioavailability of copper in seawater is highly dependent on seawater chemistry. Therefore, reductions in seawater pH due to OA will increase the toxic, free ionic form of copper in oceans by 20% by the end of the current century. These abiotic changes can have important impacts on marine biota and ecosystems. Fleshy (non-calcifying) macroalgae such as those that belong to the Order Laminariales are important components of coastal environments. Macroalgae, as sessile organisms, are exposed to constant changes in abiotic factors and the community dynamics (e.g., growth and reproduction) depend on their tolerance to stress. Despite their importance, few studies have focused on the effects of OW, OA and/or copper pollution on fleshy macroalgae and even less have focused on their early life stages. Early life stages have been reported to be the most sensitive phase of the macroalgal life cycle to stressors. Therefore, the main purpose of this work was to evaluate the separate and interactive effects of seawater temperature, pH and copper concentration on the development of microscopic stages of the native kelp M. pyrifera and the invasive kelp U. pinnatifida from southern New Zealand. The first result of this work was that, in M. pyrifera, sporogenesis occurred in basal sporophylls (specialized reproductive laminae) as well as in non-reproductive laminae such as pneumatocyst-bearing adult blade and young apical scimitars. The sorus surface area was greater on sporophylls (57%) than in adult blades and young scimitars (25%). Meiospore release was greater in apical scimitars, followed by adult blades and sporophylls. However, germination of meiospores from different laminae was not significantly different, indicating that meiospores produced in all types of fertile laminae were equally viable. The first climate change-related experiment consisted of monitoring meiospore development of M. pyrifera and U. pinnatifida cultured under four seawater pH treatments (pH 7.20, extreme OA predicted for 2300; pH 7.65, OA predicted for 2100; pH 8.01, ambient pH; and pH 8.40, pre-industrial pH) for 15 days. Reduced seawater pH (7.20 and 7.65) had no effects on meiospore germination but had positive effects on germling growth rates and gametophyte size of both species compared to higher pH (8.01 and 8.40). Gametophyte sex ratio was biased towards females under all pH treatments. Germling growth rate under OA was significantly higher in M. pyrifera compared to U. pinnatifida but gametophyte development was equal for both kelps under all seawater pH treatments, indicating that the microscopic stages of the native M. pyrifera and the invasive U. pinnatifida will respond similarly to OA. The second experiment climate change-related experiment consisted of monitoring meiospore development of M. pyrifera and U. pinnatifida cultured under four seawater pH treatments (pH 7.20, 7.65, 8.03, and 8.40) and two temperature treatments (12°C, ambient temperature; and 16°C, OW predicted for 2100) for 15 days. Reduced seawater pH and elevated temperature had no effects on meiospore development and positive effects on germling growth rates and gametophyte size of both species compared to higher pH (8.01 and 8.40) and lower temperature (12°C), whereas gametophyte sex ratio was not affected by the interaction between the two factors. Despite some small differences between species, results of this experiment suggest that microscopic stages of the native M. pyrifera and the invasive U. pinnatifida will respond similarly to OA and OW. The single effects of the local stressor, copper pollution, on the development of M. pyrifera and U. pinnatifida meiospore were examined. After settlement, meiospores of both kelps were exposed to five nominal copper treatments (control, 100, 200, 300 and 400 µg L-1 Cu) for 9 days. Analyses of total dissolved copper (CuT) concentrations in the blanks showed that nominal copper concentrations were reduced to 54, 91, 131 and 171 µg L-1 CuT (i.e., > 50% of the CuT was adsorbed onto the culture vessel walls). In the media with meiospores, the CuT also decreased: to 39, 86, 97 and 148 µg L-1 CuT in M. pyrifera, and to 39, 65, 97 and 146 µg L-1 CuT in U. pinnatifida (i.e., 6 – 15% of the dissolved copper was adsorbed by the cells). Meiospore germination decreased with increasing copper concentrations but gametogenesis was arrested under all copper treatments. The effective copper concentration causing 50% of arrested germination (Cu EC50) was higher for U. pinnatifida (231 µg L-1 CuT) than for M. pyrifera (157 µg L-1 CuT), suggesting ecological success for the invasive species in copper polluted environments; however, the subsequent inhibition of gametogenesis under all copper treatments indicated no difference in copper tolerance between both kelp early life stages. The reduction of CuT during the previous experiment occurred because copper might be adsorbed onto glass and/or plastic and this can be avoided using a proper trace metal clean procedure. Therefore, a review on the methodologies used in the literature on copper ecotoxicology of marine macro- and microalgae, specifically the use of trace metal clean procedures such as the labware used (glassware vs plasticware), methods of cleaning the labware (acid soaking and ultrapure water rinsing), stock solution preparation (copper source and acidification), and measurement and reporting of dissolved copper concentrations was performed. The main results of this review were that 50% of the articles did not specify the laboratory–ware, 25% used glassware and 25% plasticware; only ~30% of the studies specified cleaning protocols for labware to remove trace metal impurities; the copper form used to prepare the stock solutions was specified in ~80% of studies but acidification to stabilize the dissolved copper was performed in only ~20%; and the dissolved copper concentration was measured in only ~30% of studies. Based on these finding, a trace metal procedure was recommended for conducting copper ecotoxicological studies. A four-factor experiment was performed to investigate the interactive effects of OA, OW and copper pollution on the meiospore development of M. pyrifera and U. pinnatifida. Meiospores of both species were cultured under two seawater pH treatments (7.65 and 8.16), and two temperature treatments (12 and 16°C), and to the species-specific Cu-EC50 for 18 days. In both species, meiospore germination and germling growth rates significantly decreased in the copper treatment, irrespective of pH and temperature whereas gametophyte development for both species was inhibited by copper in all pH and temperature treatments. These results suggest that a local stressor (e.g., copper) is more important to the development of microscopic stages of M. pyrifera and U. pinnatifida than global climate change factors. In summary, results of this study indicate that meiospore development of M. pyrifera and U. pinnatifida will be able to tolerate future OA and OW. That tolerance might be related to: 1) macro- and microscopic stages of both kelps being able to use HCO3- and CO2 to support photosynthesis, therefore, the higher CO2(aq) availability due to OA (pH 7.20 to 7.65) will not affect their physiology; and 2) both M. pyrifera and U. pinnatifida have a wide temperature tolerance (4 to 30C°) which may allow them to perform well in a future warmer ocean (+ 4C°). In contrast, relatively high copper concentrations inhibited meiospore development of both kelp species. This finding indicates that local drivers (e.g., copper pollution) may be more important to physiological processes during meiospore development than global climate change factors. Furthermore, the responses of meiospores to the experimental abiotic factors (i.e., OA, OW and Cu) were similar between the study species, indicating that the invasive U. pinnatifida is unlikely to have an advantage over the native M. pyrifera in natural coastal environments.

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  • The use of combination tyrosine kinase inhibitors for the treatment of glioblastoma multiforme

    Nehoff, Hayley (2016)

    Doctoral thesis
    University of Otago

    Glioblastoma is the most common primary brain tumor which has a median survival of only 14.6 months. The central nervous system localization, heterogeneity of the cells and resistance to treatment constitute a significant challenge to establishing an efficient and durable therapy. Glioblastoma lesions contain a dense network of defective blood vessels which are permeable to high molecular weight constructs such as nanocarriers. Furthermore, glioblastoma lesions are known to depend upon several tyrosine kinases in order to facilitate their development, progression, invasion and treatment resistance. As a consequence, we assessed the cytotoxicity of multiple tyrosine kinase inhibitors (TKIs), singularly or in combination, against a panel of glioblastoma cell lines in vitro. The most promising combination of crizotinib, an inhibitor of Met and ROS1, and dasatinib, an inhibitor of SRC and focal adhesion kinase (FAK), were pursued as the lead compounds. In addition, these TKIs were encapsulated into polystyrene co-maleic acid micelles to improve their pharmacokinetic profiles in vivo by selective accumulation in tissues with fenestrated vasculature. The micelles were characterized based on their loading, charge, size, solubility and release rate. Both formulations were assessed for their ability to alter protein expression profiles, induce cell death and reduce proliferation. The ability of the treatments to prevent migration, invasion and angiogenesis in a panel of glioblastoma cell lines was also assessed. The micelles had favorable physicochemical characteristics, with a size sufficient to promote a prolonged plasma half-life, a near neutral charge to prevent opsonization and a steady release rate. The expression and phosphorylation of the target kinases Met, ROS1, SRC, and FAK were consistently reduced by the combination treatment. The combination treatment also reduced the expression of EGFR despite neither TKI targeting this receptor. The inhibition of these targets and subsequent suppression of downstream AKT activity induced apoptotic cell death in glioblastoma cells. The cell death following removal of the drug after a 72 h treatment period, defined as washout, was assessed to determine the ability of the cells to escape from treatment-induced cell death. Following washout, the apoptosis was maintained for 72 h following the removal of the drugs in the free but not the micellar formulations. The induction of cell death correlated with the induction of polyploidy in the free but not micellar formulations. This polyploidy was not causative of cell death but was associated with genetic instability. Both free and micellar formulations showed effective prevention of invasion, migration and angiogenesis in vitro. This study demonstrated the efficacy of the combination of crizotinib and dasatinib in a panel of glioblastoma cell lines. This combination strongly induced apoptotic cell death. Furthermore, the combination also effectively combated several treatment resistance pathways such as invasion and vascular mimicry, potentially augmenting the efficacy of the current therapies. The micellar formulations show comparable efficacy to the free formulations but also provide the potential for the improvement of in vivo pharmacokinetic parameters. In conclusion, the combination of crizotinib and dasatinib shows significant promise in vitro and warrants further investigation in vivo for the treatment of glioblastoma.

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