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    Early Life Determinants of Asthma in New Zealand Children: Finding from the Growing Up in New Zealand study

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    Background: Childhood asthma is a prevalent chronic condition affecting children of all ages. Despite advances in understanding the pathophysiology of childhood asthma, the identified risk factors vary significantly between studies and regions. New Zealand has one of the highest prevalence’s of childhood asthma globally, and inequalities in the prevalence within the country between population groups constitute a public health problem. Aims: This study had three aims. The first aim was to investigate the prevalence of childhood asthma in children aged 4½ years in the Growing Up in New Zealand cohort study and in demographic subgroups defined by maternal age, region of birth, child’s sex, ethnicity, and family socioeconomic status. The second aim was to identify potentially modifiable environmental risk factors associated with childhood asthma in the cohort children. The third aim was to determine the frequency of single nucleotide polymorphisms, known to be associated with childhood asthma, in the total Growing Up in New Zealand cohort and within European, Māori, Pacific, and Asian ethnic groups within this cohort, and conduct the analysis of association of these polymorphisms with childhood asthma. Methods: Aim 1: This study was conducted within the Growing Up in New Zealand cohort study, a contemporary pre-birth cohort study that enrolled 6,853 children born in New Zealand in 2009- 2010. For the prevalence study, children were classified as having current asthma at age 4.5 years based upon parental report and receipt of dispensed asthma medications. Subgroup comparisons of prevalence were reported using prevalence ratios (PR) and 95% confidence intervals (CI). Aim 2: To analyse environmental risk factors and assess the robustness of the findings, three asthma case definitions were used. Data collection in the Growing Up in New Zealand study took place before birth, 6 weeks after birth, and when children were 9 months, 2 years, and 4.5 years of age. Additionally, linkage to the community pharmacy prescribed medications dispensing database was made to measure dispensed asthma medications and antibiotic prescriptions. For statistical analyses of environmental data, univariable analyses, followed by multinomial logistic regression analyses, were conducted. The independent variables included in the multivariable analyses were chosen based on the available literature. Their proposed causal relationships were studied using causal inference framework and directed acyclic graphs. Independent associations were described using adjusted odds ratios (adjOR) and 95% CI. Aim 3: Children with asthma and no asthma/wheeze were genotyped for the genetic study in a case: control ratio of 1:2 and were matched based on the child’s sex and prioritised ethnic group. Saliva samples were genotyped using the Illumina Infinium Global Screening array-24 v3.0 beadchip, followed by imputation. For genetic analysis, the alternative allele frequency was calculated for each ethnic group separately. Association analysis of single nucleotide polymorphisms (SNPs) with childhood asthma was conducted in each ethnic group individually and in a total cohort. The analysis was adjusted for the first four principal components. Results: Of 6,853 children enrolled in the cohort, 82.7% (5,667/6,853) were included in this study. The prevalence of current asthma was 12.9% (732/5667). The prevalence of childhood asthma was higher in younger mothers (PR=1.40, 95% CI 1.14–1.72 for mothers aged 20-24 years and PR=1.20, 95% CI 1.00–1.45 for mothers aged 25-29 years versus mothers aged 30-34 years), in males (PR=1.53, 95% CI 1.33–1.76), in Māori children (PR=1.50, 95% CI 1.25–1.79) compared with European children, and children living in households in areas of moderate and high deprivation (PR=1.23, 95% CI 1.03–1.47, and 1.23, 95% CI 1.03–1.48, respectively) compared with low deprivation. In the multivariable analysis, emergency or unplanned C-section (adjOR=1.28, 95% CI 1.02– 1.61), eczema or dermatitis before age 2 years (adjOR=1.89, 95% CI 1.61–2.22), bronchiolitis and chest infection during the first year of life (adjOR=1.82, 95% CI 1.52–2.17 for 1-3 episodes), three or more antibiotic prescriptions during the first year of life (adjOR=1.48, 95% CI 1.19–1.84) were associated with an increased odds of childhood asthma. In total, 479 cases and 923 controls, and 122 SNPs of interest passed pre- and post-imputation quality controls and were included in the final genetic analysis. There was differences in the alternative allele frequency between all ethnic groups within the Growing Up in New Zealand cohort. The largest differences in allele frequencies were observed between the New Zealand European and Pacific ethnic groups. Similar differences were observed between 1000 Genome European reference panel and ethnic groups from the Growing Up in New Zealand cohort. The SNPs associated with childhood asthma in the Growing Up in New Zealand study varied between ethnic groups: 48 SNPs were associated with childhood asthma in the New Zealand European ethnic group, 44 in the Māori ethnic group, 7 in the Pacific ethnic group and 7 in the Asian ethnic group. In total, 69 SNPs were associated with childhood asthma in the overall Growing Up in New Zealand cohort. Conclusion: Based upon a cohort broadly generalisable to the national birth cohort, the prevalence of childhood asthma in New Zealand at age 4½ years is 12.9%. Childhood asthma prevalence varies with maternal age, child ethnic group and household deprivation. Emergency or unplanned C-section, eczema or dermatitis before age 2 years, bronchiolitis and chest infection during the first year of life, and three or more antibiotic prescriptions during the first year of life were associated with increased odds of childhood asthma. The SNPs associated with childhood asthma differ between ethnic groups in New Zealand. Further studies are required to understand the mechanisms of how modifiable risk factors affect the development of childhood asthma in New Zealand, and the relative and/or cumulative contribution of environmental and genetic factors to childhood asthma prevalence’s in New Zealand

    Three-dimensional virtual histology of the rat uterus musculature using micro-computed tomography

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    Contractions of the uterus play an important role in menstruation and fertility, and contractile dysfunction can lead to chronic diseases such as endometriosis. However, the structure and function of the uterus are difficult to interrogate in humans, and thus animal studies are often employed to understand its function. In rats, anatomical studies of the uterus have typically been based on histological assessment, have been limited to small segments of the uterine structure, and have been time-consuming to reconstruct at the organ scale. This study used micro-computed tomography imaging to visualise the muscle structures in the entire non-pregnant rat uterus and assess its use for 3D virtual histology. An assessment of the rodent uterus is presented to (i) quantify muscle thickness variations along the horns, (ii) identify predominant fibre orientations of the muscles and (iii) demonstrate how the anatomy of the uterus can be mapped to 3D volumetric meshes via virtual histology. Micro-computed tomography measurements were validated against measurements from histological sections. The average thickness of the myometrium was found to be 0.33 ± 0.11 mm and 0.31 ± 0.09 mm in the left and right horns, respectively. The micro-computed tomography and histology thickness calculations were found to correlate strongly at different locations in the uterus: at the cervix, r = 0.87, and along the horn from the cervical end to the ovarian end, respectively, r = 0.77, r = 0.89 and r = 0.54, with p < 0.001 in every location. This study shows that micro-computed tomography can be used to quantify the musculature in the whole non-pregnant uterus and can be used for 3D virtual histology

    Investigating ester bond formation in bacterial adhesin domains

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    The adhesin proteins of Gram-positive bacteria are crucial for adhesion and colonization by mediating host cell interactions. These molecules are long and narrow and often made up of many Ig-like protein domains like beads on a string. The Ig-like proteins typically contain intramolecular cross-links including isopeptide, thioester, and ester bonds, that are typically formed between the first and last β-strands of the Ig-like domain. These cross-links help bacterial to withstand mechanical forces, and chemical and proteolytic action in their environment during host cell targeting. The mechanism of ester bond formation resembles that seen in serine proteases. This MSc project focuses on the mechanism and applications of ester bond formation in Gram-positive bacterial adhesins with two aims. The first aim was to better understand the enzymatic mechanism by characterizing new adhesins in nature. The second aim was to assess the potential of small peptide molecules to interfere with native cross-linking in adhesins as a potential antimicrobial mechanism. To explore the enzymatic mechanism, laboratory experiments and computational simulations were conducted. A total of 468 proteins from identified within the UniProt database, and 216 potential cross-linked proteins closely examined for cross-linking potential. Two candidate proteins were experimentally validated to confirm ester bond formation, with cross-linking observed in one of these, although this was not confirmed definitively. Mutagenesis was attempted to enhance cross-linking in this domain with the conclusion that this protein may form a different kind of cross-link, e.g. an isopeptide bond, or than an ester bond cross-link forms through a different mechanism. Molecular dynamics (MD) simulations provided mechanistic clues to the first step of the reaction mechanism, proton abstraction, with the rotation of the catalytic base, histidine observed. The results show that the basic histidine can transiently flip and approach the nucleophile threonine forming a hydrogen bond, the step just before proton abstraction. MD was further used to validate the proposed antimicrobial strategy. Simulations followed the ability of the final β-strand of the protein in a partially unfolded protein, to fold down into place and reform the protein structure. These preliminary experiments showed some of the folding expected, but suggested more sophisticated methods should be used in future simulations

    Seismic Resilience of Buildings in Nepal combining Traditional Practices and Modern Engineering Principles

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    Organised earthquake risk management remains limited in many developing countries, leaving them vulnerable to significant human and financial losses due to seismically deficient buildings. Enhancing the seismic resilience of buildings is therefore essential. Through a series of published articles, this thesis presents an investigation on seismic safety aspects, including community-based disaster risk reduction (CDRR), seismic simulation tools suited to resource-limited settings, and the development of cost-effective, seismic-resilient building techniques. The first part of the thesis examines earthquake risk reduction efforts in Nepal, focusing on community strategies and policy frameworks. This research identifies CDRR approaches and intervention strategies that can be applied in other seismically active regions. Analysis of vernacular masonry buildings along the 2,400 km Himalayan arc, supported by empirical data and qualitative analysis reveals that traditional construction materials and techniques can significantly enhance seismic resilience. This section also identifies practical simulation tools, such as shock table, harmonic shaking table and controlled underground explosions, for dynamic testing of building structures in developing countries. The second part of the thesis addresses reconstruction strategies for school buildings in remote mountainous areas affected by the 2015 Gorkha earthquake, advocating the use of locally available materials and techniques. A guideline on attribute-based method was developed for selecting construction materials, skills, and building typologies for post-earthquake reconstruction. Experimental research on stone masonry set in mud mortar and contained by steel wire mesh demonstrated enhanced strength, deformability, and energy dissipation capacity of the masonry. Additionally, shaking table tests on reduced-scale school building models featuring stone masonry walls set in mud mortar contained in wire mesh and reinforced with gabion mesh bands validated the effectiveness of the seismic strengthening approach suitable for high seismic regions. Collectively, these studies contained in this thesis validate that integration of traditional materials and construction with modern engineering methods and innovation can yield effective earthquake-resilient buildings. While the focus of the current research is Nepal, it proposes a model for other developing countries facing similar seismic challenges, advocating resilient communities through a balance of traditional practices and modern engineering innovations. Findings demonstrate that combining traditional knowledge with innovative engineering offers promising solutions for seismic resilience

    High school counsellors' perceptions of the barriers and enablers that rainbow young people face when accessing counselling

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    Rainbow youth experience disparities in mental health, with over half of LGBTQIA+ youth in New Zealand, particularly transgender and gender-diverse individuals, reporting difficulty in accessing adequate healthcare in the past 12 months (Fenaughty et al., 2021). Furthermore, an earlier Ministry of Youth Development (2015) report highlighted the challenges faced by young people questioning their sexual identity who experience significantly more long-term mental health challenges compared to their heterosexual peers. Collectively, the research highlighted the need for societal and school environments to shift to become more inclusive, as fear of discrimination reduced the likelihood these young people would seek support. Research by Fenaughty et al. (2019) indicated that sexual and gender minority students report lower academic achievement compared to other students, potentially due to increased victimization and less sense of belonging at school. However, the same research also suggested that supportive school environments and parental backing can positively impact academic outcomes for LGBTQIA+ youth. School counsellors can be an essential part of producing a positive school environment for LGBTQIA+ youth if these young people can access them. The current study explores the challenges LGBTQIA+ youth encounter when accessing mental health support in schools through interviews with six high school counsellors. The thematic analysis of the interviews revealed four main themes: 1.) Structural challenges within schools that hinder inclusivity. 2.) Professional challenges faced by school counsellors. 3.) Counsellors need to increase their visibility to engage LGBTQIA+ youth. 4.) Counsellors must build positive relationships with school staff to improve LGBTQIA+ youth engagement. Recommendations from the outcome of this study included allowing counsellors to be a part of deciding the professional development outcomes for staff, including LGBTQIA+ engagement work, and secondly, setting expectations within schools regarding the counselling role to reduce the chances of ethical conflicts for counsellors. Further recommendations included training counsellors to be better informed about working in high schools and with LGBTQIA+ youth and increasing training opportunities for school staff regarding the importance of safe spaces. The study aims to provide insight into the barriers facing LGBTQIA+ youth, discouraging them from seeking support from high school counsellors while also discovering the enablers that allow them to feel able to access support

    Integrating Human-Centred Design and Therapeutic Approaches in Dementia Care: Enhancing Quality of Life Through Architecture and Planning

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    As New Zealand’s elderly population grows, the number of people with dementia will also increase, resulting in a rising demand for dementia care. However, many existing care facilities are designed with an institution that feels impersonal and fails to address the well-being of individuals with dementia. This not only impacts their quality of life but also places additional strain on caregivers and the already strained healthcare system of New Zealand. Therefore, there is an urgent need for a more effective and compassionate dementia care model that focuses on human-centred design and therapeutic practices. This thesis explores how a human-centred approach in architectural design can enhance the quality of life for people with dementia. The concept of human-centred design is to create environments that address the needs and experiences of individuals and support overall well-being. Equivalently, validation therapy is a relatively new approach based on empathy, respect, and recognition of the feelings of individuals with dementia; it has been shown to reduce distress and improve emotional well-being for those with dementia. Integrating these two approaches can be very promising in creating a care model that is both supportive and fulfilling for individuals with dementia. This research investigates how the built environment, through elements like materials, lighting, spatial layout, wayfinding cues and sensory stimulation, can support the principles of validation therapy. Three primary research methodologies will be used - Research through literature, precedents and design. By examining secondary data from literature reviews, architectural precedents, and case studies of successful dementia care facilities, this study aims to understand how design and therapeutic practices can positively influence the living experiences of people with dementia. The findings suggest that the combination of human-centred design and validation therapy contributes positively to the four key aspects of well-being for people with dementia: Identity, autonomy, stimulation and connection to the community. The thesis proposes a practical framework for integrating the two approaches into dementia care centres and advocates for further research on their combined impact

    Alex Monteith & Maree Sheehan [Transformative Currents: Art and Action in the Pacific Ocean]

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    The chapter contribution provides context, artwork production still images and exhibition installation images, for the interdisciplinary video installation which explores marine biodiversity in Taranaki, Aotearoa New Zealand. Collaborating with Taranaki Iwi's Te Kāhui o Taranaki Takutai Kaitiaki (coastal custodians), the artists investigate the ecological impact of settler-colonial land mismanagement on aquatic ecosystems. The installation focuses on the critical junction where Te Whanganui river meets Ngā Tai a Kupe and Te Tai-O-Rehua, documenting the paradoxical role of water currents as both life-sustaining forces and vectors of pollution. Through multi-channel video and sound techniques, the work adopts the perspectives of local aquatic species—tuna (eels), īnanga (whitebait), kōaro, and koura (crayfish)—revealing their navigation of and adaptation to polluted environments. The installation's curved monitor arrangement mimics the movement patterns of tuna, highlighting their remarkable adaptability despite environmental degradation. These long-lived creatures, which can survive up to 90 years, perceive changes in water currents through specialized lateral lines, literally "feeling" the effects of human pollution across generations. The sonic component integrates recordings captured via binaural microphones, hydrophones, and geophones, presenting auditory information beyond normal human perception and exposing the acoustic signatures of climate change and environmental destruction. This methodology addresses knowledge gaps identified by New Zealand's Department of Conservation regarding Taranaki's offshore marine ecology, demonstrating how sonic and visual technologies can document previously inaccessible underwater environments

    Platform imperialism and disinformation in Aotearoa-New Zealand

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    This article looks at how the emergence of the disinformation field in Aotearoa-New Zealand is indicative of the territorial power of American platforms in policy settings. The country has been a key flashpoint in the debates around platform harm. Former Prime Minister Jacinda Ardern was a champion of technocratic and compassionate leadership in navigating the country through the Christchurch mosque terror attack and COVID-19. At the heart of Ardern's political legacy was The Christchurch Call and adopting a ‘whole of society’ approach to fighting disinformation. In her on-going work she stands as a post-political, moral leader in fostering stakeholder conversations around platform harm, emerging tech and disinformation. This mode of governance is indicative of platform imperialism during the post-2016 Techlash. It is an administrative paradigm that views civil society partnership and big data epistemologies as the means to protect democracies rather than anti-trust measures or domestic platform and media policies. The lead policy entrepreneurs in the field of disinformation research in Aotearoa-New Zealand were The Disinformation Project (TDP). Their role was to furnish local media, government and researchers with a lexicon of “infection” and “subversion”, within which political conflicts are viewed as epiphenomena of disinformation warfare. The field is characterised by a moral, post-political discourse that perpetuates a fantasy of social wholeness and treats platforms as unalterable entities rather than dependent on regulatory carve-outs and arbitrage. The utility of this administrative research is on the wane as the Techlash window of opportunity has closed and with it research centres like TDP

    Follow Your Gut - An Investigation of the Role of Architecture on Human Decision-Making and Intuitive Wayfinding

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    Airports are functional environments designed to facilitate the seamless movement of passengers from landside to gate, with wayfinding systems playing a crucial role in ensuring the efficient movement of passengers. Modern terminals heavily rely on signage to guide passengers through them. The otherwise direct relationship between people and space is replaced by abstract media such as text and symbols, often leading to information overload and confusion, resulting in a stressful travel experience. However, spaces can communicate information directly to occupants through spatial features that shape individuals’ decision-making and influence behaviour. People navigate and interpret spaces following instinctual understandings born out of evolutionary traits. By designing architecture that addresses these instincts, spaces can subtly influence subconscious decision-making. Follow Your Gut investigates the impact of architecture on passengers' decision-making and wayfinding behaviours in the context of the check-in area of Auckland Airport International Terminal. The project aims to integrate spatial and visual cues into the architectural design to facilitate intuitive wayfinding for outbound passengers. It is scoped as a redesign within the existing footprint, addressing current wayfinding challenges to create a more intuitive journey while reducing passengers’ cognitive load. The research explores human perception and spatial cognition, analysing how the built environment influences decision-making. These insights are distilled into a set of guiding principles, which are then used to evaluate existing public spaces. The findings inform an iterative design process, culminating in a project that applies intuitive wayfinding theories while ensuring practical feasibility for an efficient check-in area at Auckland Airport’s International Terminal

    Properties of the Extracellular Annelid Haemoglobin (M101) from the Marine Worm Arenicola marina

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    The blood of the marine worm Arenicola marina has remarkable properties that can improve transplantation outcomes. It has been used as a bio-therapeutic tool in surgery. The process of organ transplantation faces challenges such as ischemia-reperfusion injury (IRI), which are caused by organ hypoxia, mitochondrial damage and the production of toxic reactive oxygen species (ROS). The M101 protein in Arenicola marina blood could be used to ameliorate IRI during organ transplantation by having a high affinity for oxygen and a high oxygen-carrying capacity as well as the ability to inhibit the ability to suppress the immune response, providing a new way in the field of organ transplantation. This study aims to investigate whether M101 can deliver oxygen to anoxic mitochondria and buffer mitochondrial ROS production, and explain its role in the management of IRI in organ transplantation. The project used oximetry and spectrophotometry to simulate mitochondrial ischemic conditions and measure whether M101 can deliver oxygen to anoxic/hypoxic mitochondria and to inhibit ROS production effectively. This research is important for improving the success rate of organ transplantation and saving more lives. This study found that M101, as an antioxidant, is stable in nature and can reduce organ and tissue damage during transplantation and IRI by reducing oxidative stress and enhancing the oxygen affinity of mitochondria. This makes M101 show unique advantages over conventional antioxidants in organ transplantation. The dual function of combining antioxidant properties and oxygen-carrying capacity makes M101 particularly effective in transplantation and IRI environments. These properties are critical for post-transplant recovery and prolonged organ survival. Notably, in hypoxic or low-oxygen environments, the enhanced oxygen affinity of M101 ensures that mitochondria continue to maintain a membrane potential, synthesising adenosine triphosphate (ATP), which is critical during organ ischemia or recovery from hypoxia. The optimal antioxidant effect of M101 is within a two-hour period, suggesting that it is best to limit the use of M101 to this time frame when using M101 for organ preservation

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