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    The use of child oral-health-related quality of life measures in a randomised control trial of the Hall crown technique in a primary care setting

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    The first aim of this thesis was to analyse the health-related (HRQoL) and oral-health-related quality of life (OHRQoL) information collected during the clinical trial of the Hall technique, to determine whether there were differences between those receiving conventional dental treatment (restorations and conventional stainless-steel crowns), and those having the Hall technique of stainless-steel crown placement. The second aim was to see whether the current child HRQoL and OHRQoL measures were responsive to routine dental treatment in the primary health setting. Method The Transform a Tooth (TAT) study was undertaken in the Whanganui District Health Board Community Oral Health Service (COHS) from 2014-2018 by Dr LA Foster Page and Dr DH Boyd, with funding from the Cure Kids Foundation and support from 3MTM. It was a randomised control trial, investigating the use of the Hall technique for the placement of preformed stainless-steel crowns on children’s primary teeth to treat dental caries. The children involved in the study were aged 3-7 years at the time of recruitment. Prior to the initial appointment consent was obtained, and questionnaires were completed. A clinical examination was undertaken where the baseline oral health data was recorded, and posterior bitewing radiographs were taken. Those children who met the selection criteria, were randomly allocated to the test group (Hall) or control group (non-Hall) and proceeded to have their treatment. The children had subsequent dental examinations and completed repeat OHRQoL questionnaires at the 12-month, and 24-month follow-up appointments. Data from the clinical aspects of the trial are presented elsewhere. The parent questionnaire used in the TAT study contained five components. This included a global question on oral health impact, the short-form 16-item Parent/Caregivers Perceptions Questionnaire (P-CPQ) on OHRQoL, a short form version of the Family Impact Scale (FIS) consisting of eight questions on how oral health may have impacted family life, a global question on how the child’s oral health affects the family, and nine questions on the child’s general quality of life, collected using the Child Health Utility 9D (CHU-9D). The initial parent questionnaire also included the Index of Socioeconomic Deprivation (NZiDep) questions. The child questionnaire included the CHU-9D (child version) of nine questions relating to the child’s quality of life, the seven question Scale of Oral Health Outcomes (SOHO), and five general ‘global’ questions. The OHRQoL questionnaires were administered initially prior to selection into the study, and then repeated at the 12-month and 24-month follow-up appointments. Findings The children included in the study differed from those excluded by: being more likely to be from a high deprivation area (area-deprivation method only, no difference was found using the household deprivation method), having higher caries experience (respective dmft scores of 4.6 and 1.4), and higher mean OHRQoL scale scores on the both the P-CPQ and SOHO scales. The two randomised treatment groups of Hall (51% of included sample) and non-Hall (49%) had no significant differences in their demographic characteristics, caries experience or mean HRQoL/OHRQoL scale scores. The HRQoL/OHRQoL measures were tested for internal consistency using Cronbach’s alpha co-efficient. The P-CPQ had the strongest score (0.82), and the CHU-9D child version the lowest (0.63). At the 12-month follow-up there were 129 (92%) remaining in the Hall group, and 129 (88%) in the non-Hall group. There was a significantly higher proportion of Māori children lost to follow-up. For those followed up at 12 months, all repeat HRQoL/OHRQoL questionnaires showed slightly higher mean scale scores for the Hall group, with statistical significance for the CHU-9D parent measure. Change scores and effect sizes for the P-CPQ and FIS had small improvements for both Hall and non-Hall groups. The CHU-9D parent version Hall had a small worsening and the non-Hall had a small improvement. The CHU-9D child version Hall group had a moderate worsening and the non-Hall a small worsening. For the SOHO scale the Hall group had a small worsening and non-Hall a small improvement. By the 24-month follow-up fewer than half of the participants remained, with 43% and 48% (respectively) retained in the Hall and non-Hall groups. Despite this relatively high attrition rate there were no statistically significant differences in their demographic characteristics, caries experience or baseline mean HRQoL/OHRQoL scores for those assessed and those lost to follow-up. At that 24-month follow-up the Hall group had higher mean HRQoL/OHRQoL scale scores for three of the measures (P-CPQ, CHU-9D parent, and SOHO) than the non-Hall. The change scores and effect sizes at 24 months for both groups had moderate improvement in their mean the P-CPQ scores, and small improvements in their FIS scores. The CHU-9D parent version had no change for the Hall group and small improvement in the non-Hall, and the SOHO score had no change in the Hall group and small improvement in the non-Hall. The CHU-9D child measure had a small worsening for the Hall group, and moderate worsening in the non-Hall group. However, none of the differences were statistically significant. Conclusions The HRQoL/OHRQoL information is an important adjunct to the clinical data collected during clinical trials. It provides valuable information on the impact that different treatment modalities have on children and their families. This is important when new clinical techniques are being considered, such as the Hall technique, which should not be judged just on its clinical success or failure. It is important to consider the timeliness of the questionnaires with regard to the treatment intervention, and whether we can directly infer the studied intervention technique without allowing for the confounding variables over the period of a year. The children receiving the Hall crown treatment technique after 12 month had higher scale scores, but this effect was not clear at the 24-month review, with mixed results between the two groups. The P-CPQ was the only measure which did not have a large floor effect in the scale scores, and had the best internal reliability. The P-CPQ score showed a small improvement at 12-months and moderate improvement at 24 months in both the Hall and non-Hall groups. The P-CPQ may be the best measure suited to this younger age group (age 3-8) in this scenario type (routine dental treatment in primary care setting). Careful consideration needs to be given to whether these measures have the responsiveness to identify any meaningful change

    Crohn's disease: an in vitro analysis of T lymphocyte function and response to commensal microbes

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    Inflammatory bowel disease is a chronic, relapsing inflammation of the intestine. Approximately 0.5% of the western world is estimated to suffer from the disease. Crohn’s disease, a type of inflammatory bowel disease, consists of a patchy inflammation, that can occur throughout the entire gastrointestinal tract. Due to the heterogeneous nature of Crohn’s disease, little is known about the mechanisms of disease pathogenesis. Compared to healthy individuals, patients with Crohn’s disease often have elevated levels of inflammatory T lymphocyte subsets, their associated effector cytokines, and higher intestinal permeability. Crohn’s disease has been associated with genetic risk factors, sedentary lifestyles, and a loss of tolerance to the commensal members of the microbiome. In this research, T lymphocytes from non-IBD and Crohn’s disease patient peripheral blood mononuclear cells (PBMCs) were analysed for comparison. Flow cytometry was used to fluorescently label cells and analytes of interest. Visual analytic tools, such as CytoAnalytics’ EarlyBird and viSNE were used to visualise patient variation within, and between groups. It was hypothesised that Crohn’s disease T lymphocytes would have a bias for inflammation-inducing T lymphocyte subsets, and that these cells would have a higher capacity for inflammation, than non-IBD controls. Indeed, inflammatory T lymphocytes were present at higher frequencies in Crohn’s disease patient blood samples. Furthermore, Crohn’s disease patient PBMCs had a higher capacity for proliferation in response to T lymphocyte stimulation. In responses to the commensal bacterium, Faecalibacterium prausnitzii, Crohn’s disease patient PBMC Tregs increased in frequency, whereas CD4+ inflammatory T lymphocyte subsets maintained their frequency. In contrast, non-IBD PBMC Tregs were not influenced by co-culture with F. prausnitzii, and CD4+ inflammatory T lymphocyte subsets decreased in the presence of F. prausnitzii. Together, these data suggest that Crohn’s disease patient PBMCs respond abnormally to commensal bacteria, and this could play a role in disease pathogenesis. Intestinal organoids are derived from patient colonic biopsy stem cells. Organoids provide a unique in vitro model for the observation of intestinal interactions. In this thesis, a 2D intestinal monolayer was developed from the culture of 3D intestinal organoids. 2D monolayers emulate epithelial intestinal barrier cellular organisation. A difficult question to answer in Crohn’s disease research is whether intestinal permeability and inflammation is a cause or consequence of disease. As such, patient organoids and bacteria were integrated into the model stepwise, to analyse the influence each component has on the system, in the absence, or presence, on an active immune presence. Using this model, it was found that monolayers derived from Crohn’s disease patients were more permeable than non-IBD controls. Furthermore, Crohn’s disease patient monolayers had deleterious interactions in co-culture with F. prausnitzii, resulting in reduced epithelial integrity; in contrast to non-IBD patient monolayers which were unaffected. The addition of matched PBMCs into Crohn’s disease patient monolayers exacerbated epithelial degradation in the presence of F. prausnitzii. Taken together, it was found that Crohn’s disease patient PBMCs had greater inflammatory capacity than non-IBD control PBMCs. These data suggest that intestinal cells in patients with Crohn’s disease may have deleterious interactions with commensal bacteria, which could result in increased intestinal permeability. Furthermore, Crohn’s disease patient Treg responses to commensal bacteria suggest that intestinal areas of immune suppression may promote bacteria success, and potential dysbiosis. Translocation of the luminal microbiota into the lamina propria, combined with excessive T lymphocyte inflammatory capacity, could be an initial driving factor for Crohn’s disease pathogenesis. Data in this thesis provide valuable insight into the initiation of epithelial degradation in patients with Crohn’s disease. These data suggest that epithelial degradation may occur in Crohn’s disease patients in response to commensal bacteria, even in the absence of an immune cell influence. With further development, the intestinal organoid monolayer model may provide insight into the mechanisms of epithelial degradation in individual patients. Further, the monolayer model may also provide a tool to optimise individual patient treatments, in vitro

    New Zealand’s vocational Rural Hospital Medicine training program: the first ten years

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    Aims: The Rural Hospital Medicine Training Programme (RHMTP) was established in 2008 to develop NZ’s rural hospital medical workforce. This study evaluates the RHMTP’s first ten- year outcomes. Methods: A mixed-methods descriptive study. Database interrogation of the Royal New Zealand College of General Practitioners records; University of Otago’s e-Vision; Medical Council of NZ register of doctors. A survey of trainees who had graduated or withdrawn. Survey questions included: current scope and place of employment; undergraduate rural experience; and trainee experiences. Results From 2009-2018, 98 doctors entered the RHMTP: 29 graduated, 20 withdrew and 49 are active registrars. Of the graduates, more than half (17/29) also completed GP training. Overall survey response rate: 80% (39/49), graduate response rate 97% (28/29). Of currently practicing graduates 92% (24/26) are working in rural NZ, most (22/24) in rural hospitals. Trainees value the RHMTP’s flexibility and breadth of clinical exposure. Main challenges relate to a lack of alignment of training requirements and funding. Conclusions. In its first decade the RHMTP has been successful in generating a rural hospital workforce and the programme is steadily growing. Attention to existing barriers is needed to ensure the RHMTP can reach its potential to benefit all of NZs rural communities.Peer Reviewe

    Cognitive impairment and conversion to dementia in Parkinson's disease: an imaging study of amyloid PET and diffusion MRI

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    Objective To investigate the association between amyloid deposition or white matter degeneration with cognitive impairment and conversion to dementia in Parkinson’s disease (PD). Background Cognitive decline and dementia are common in Parkinson's disease, however the pathophysiological basis of cognitive impairment in PD is unresolved. The time-course from diagnosis to development of dementia is highly variable, and imaging biomarkers are urgently needed to assist estimation of long-term cognitive outcomes, and enable targeted therapeutic interventions in early disease. Misfolded beta-amyloid protein aggregates, or amyloid plaques, are a significant pathology in Alzheimer's disease, and may play a part in future cognitive decline in PD. Measures of cerebral blood flow and white matter micro- and macro-structural degeneration may correlate more directly with current cognitive impairment, and may interact with amyloid to affect cognitive decline in PD. This thesis comprehensively investigates these measures in PD and aims to differentiate pathology and age-related effects, using both cross-sectional and longitudinal (three-year) study designs. Methods We acquired [18F]-Florbetaben (FBB) amyloid PET, arterial spin labelling perfusion MRI, and structural MRI in 115 patients with Parkinson’s disease, recruited from the Movement Disorders clinic at the New Zealand Brain Research Institute. Movement Disorders Society level II criteria were used to classify PD patients as having normal cognition (PDN, n=23), mild-cognitive impairment (PD-MCI, n=76), or dementia (PDD, n=16), at study baseline and over the course of three-year neuropsychological follow-up. The relationship between amyloid deposition and cognitive classification, global cognitive ability, cerebral blood flow, and conversion to dementia during the three-year follow-up was assessed using both Bayesian regression and whole-brain voxel-wise analysis. High angular resolution diffusion imaging (HARDI) MRI was acquired in a wider cohort of 123 PD participants and 37 controls, for the investigation of white matter integrity in PD across the cognitive spectrum (PDN, n=46; PD-MCI, n=66; PDD, n=11). Cross-sectional fixel-based analysis investigated measures of fibre density, fibre cross-section, and combined fibre-density-cross-section across PD, controls, and PD cognitive subgroups. Clinical measures of global cognitive ability and motor impairment were also assessed for association with these fixel-based metrics. Results We observed significantly higher cortical amyloid accumulation in our PDD group relative to other cognitive subgroups, but model comparison indicated this was due to an effect of age. Cortical amyloid was seen to be present in PD at levels comparable to healthy ageing. Longitudinal assessment identified that, while increased cortical and subcortical amyloid was associated with conversion to dementia within three years, this did not represent a clinically relevant effect. There was no evidence of an interactive effect of amyloid with cerebral blood flow to affect cognition. Reduced fibre density in the substantia nigra correlated with disease, however age exhibited the most widespread association with white matter metrics in this cohort. Conclusions This thesis investigated the effect of amyloid on cognitive impairment within a large, well-characterised, longitudinal PD cohort, and subsequently challenged existing characterisations of regional amyloid deposition relating to cognitive decline. This work also represents the largest application to-date of fixel-based analysis for the investigation of white matter degeneration across the cognitive spectrum in PD

    Identifying genes underlying adaptive traits of bulbing and bolting in onion (Allium cepa L.)

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    Onion (Allium cepa L.) is a biennial plant and completes its life cycle in two growing seasons i.e., forms bulbs in the first year and flowering and seed production occurs in the second year. The poor adaptation of onion cultivars at different latitudes results in substantial losses due to reduced yield and precocious flowering. Onions form bulbs when grown under inductive daylength and an adequate amount of far-red light. Onion cultivars grown at particular latitudes require minimum critical day length to form a bulb. At the physiological level, bulb initiation in temperate regions is regulated in a similar manner to the photoperiodic flowering of Arabidopsis (Mettananda and Fordham, 1997; Taylor, 2010; Lee et al., 2013). The first aim of this study was to identify photoperiodic pathway genes responsible for the adaptation of onion under different daylength. The expression of photoperiodic pathways gene was measured under the long-day and short-day condition in DH2150 (long-day onion) and Albasile (short-day onion) over a 24 hours period using RT-qPCR. Two FT genes (AcFT1 and AcFT4) regulate bulbing in long-day and short-day onions but respond differently under different daylength. Consistent with their proposed roles, the diurnal experiment suggested that AcFT1 and AcAP1 are only expressed in bulbing, whereas AcFT4 is expressed in non-bulbing population. The photoreceptor, circadian clock, and output pathway genes follow diurnal expression patterns peaking at different times of the day and these genes were not altered in bulbing and non-bulbing populations indicating that they are not involved in the adaptation of two onion cultivars studied here. To determine the functional role of genes is very challenging in bulb onion due to lack of an efficient genetic transformation method (Eady, et al., 2000; McCallum, 2007). The second aim of this study was to develop an efficient and reliable protocol for generating transformed onion callus cells from shoot tip tissue of germinating seed. Callus was induced efficiently from the two onion cultivars: PLK (Pukekohe long keeper) and DH2107 using Agrobacterium tumefaciens strains GV3101 and EHA105. Premature flower¬ing before bulb development is an undesirable trait and reduces the quality of the bulbs. Baldwin et al., (2014) found AcBlt1 locus on chromosome 1 which is responsible for bolting. Khosa (2018) found AcVRN1 gene is important for onion flowering. AcVRN1 gene turns on by vernalization but optimum temperature for vernalization varies. The third aim of this study was to develop a molecular marker for the AcVRN1 gene to identify which onion cultivar are susceptible to bolting at early stage of onion development. TAIL-PCR was used to amplify the unknown promoter and intron 1 region. No polymorphism was found in the promoter and intron 1 region of AcVRN1 gene in all the seven varieties studied here. Overall this study will help to understand molecular and genetic difference between LD and SD onion cultivars, which is important for adapting new onion cultivars at different latitudes

    The Archaeology of Porcellanite in New Zealand

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    Porcellanite is a lithic material that was used by early Māori to manufacture flake tools in Murihiku. This thesis examines how porcellanite was procured during the early colonisation of Murihiku. How lithic sources were utilised is important for studying the colonisation of new landscapes, as lithic sources begin as unknown variables at the onset of colonisation. Known porcellanite source sites were surveyed and material was archaeologically and geologically characterised, since the quality, form and availability of raw material influences the lithic production process. Evidence regarding how material was procured was identified, as decisions made at lithic procurement sites impact all subsequent aspects of a subsistence system. Raw porcellanite samples were collected from surveyed source sites and were subject to hand-specimen characterisation and pXRF analysis. pXRF analysis of porcellanite was highly experimental, but the results showed confident separation between the known porcellanite sources. A small porcellanite flake assemblage from the Shag River Mouth site was also analysed by pXRF and the majority of artefacts were positively correlated with the known source samples. The research of this thesis assessed how archaeologically recorded porcellanite sources were utilised, and in turn, this helped to better understand landscape exploration, settlement patterns and resource use strategies

    Thermal Selection of Seneca Valley Virus Gives Rise to a Novel Thermostable Mutant

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    This project aimed to improve the stability of the novel oncolytic virus, Seneca Valley virus (SVV). This was with the overarching goal of determining the residues and mutations thereof within the viral capsid that are responsible for capsid stability, to inform the future production of SVV Virus-Like Particles (VLPs) for use as a drug delivery vector. The thermal stability of wild-type SVV-001 was first investigated to determine a baseline to which thermostable mutants could be compared, and to inform a regimen of heating and passage to derive thermostable mutants. During optimisation of these initial experiments, heating of a sample containing approximately 107 PFU/mL SVV-001 to 58.5 °C for 30 minutes produced a single viral plaque. Virus collected from this plaque was shown to be resistant to heating at 56 °C, an improvement on the wild-type, which was shown to lose approximately 99% viral titre to heating at 53.5 °C for 30 minutes. This thermostable phenotype was also confirmed using Particle Stability Thermal Release Assays (PaSTRy). Attempts to select for increasingly thermostable virus were unsuccessful. Mutant virus was purified and the capsid-coding region of the genome sequenced. This revealed four mutations in the thermostable mutants. One of these mutations, A1776G, was predicted to have an effect on the maturation of capsid proteins, which was supported by initial results of SDS-PAGE gel analysis. The other three mutations were either synonymous mutations well-conserved in Senecavirus isolates, or outside of the capsid coding region of the genome, and so were of limited applicability to the production of VLPs. Thermostable virus was then optimised for cryo-electron microscopy to determine its structure, with a low-resolution structure derived as a proof-of-principle. Future studies are warranted to determine if the A1776G confers a thermostable phenotype to the wild-type virus, and in turn to the SVV VLP. The basis for this phenotype should also be investigated, as well as a means to introduce the desired drugs into the genomeless capsid

    Effect of pulsed electric fields on potato chips processing

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    This thesis aims to investigate how pulsed electric fields (PEF) at low field strength (E < 1.5 kV/cm) influences potato processing. The impact of PEF and potato cultivars on the colour development during frying of potato chips was studied thoroughly. The impacts of PEF on the properties of starch granules located inside the potato tissue was also investigated. Four potatoes cultivars – Russet Burbank, Nadine, Moonlight and Crop-77 – were chosen to study the effect of PEF on colour development during frying, due to their distinct differences in chemical composition such as dry matter content, total starch, amylose, glucose and total amino acids. PEF treatment was conducted on peeled potato at an electric field strength of 1 kV/cm, 20 µs pulse width, frequency of 50 Hz and different specific energy inputs of 50 kJ/kg (PEF Low) and 150 kJ/kg (PEF High). After being PEF-treated, potatoes were sliced (1.0 ± 0.5 mm thickness), blanched (boiling water for 3 min), pre-dried (75 °C for 10 min) and fried at temperatures of 150 – 190 °C for different time intervals. It was found that PEF processing did not change the first-order kinetics of the colour (L*) change of potato chips made from the four cultivars. The inherent differences in reducing sugar and amino acids content are the important factors influencing the estimated kinetic rate constant (k) of changes in parameter L* during frying, showing Nadine having the fastest rate and Crop-77 having the slowest rate of darkening regardless of the frying temperature. Depending on the cultivars, PEF treatment combined with blanching affected the estimated k and Arrhenius activation energy (Ea) values. Combined PEF and blanching treatment decreased the estimated Ea values for Russet Burbank and Crop-77. The intensity of Maillard reaction that occurred during frying was further studied using the volatile profile obtained in the headspace fraction of potato chips fried for 4.5 min in the temperature range of 150 and 190 °C. From a total of 76 volatile compounds identified across cultivars, it was found that the volatile compounds came not only from Maillard reaction but also from thermal degradation of fatty acids. (Alkyl) Pyrazines dominated the volatiles from Russet Burbank, Moonlight, and Crop-77, while Strecker aldehydes dominated those from Nadine. Alkylpyrazines are considered as precursors for acrylamide that is considered to be carcinogenic. Increasing frying temperature from 150 to 190 °C enhanced the occurrence of Maillard reaction to the final stage with increased pyrazine formation and decreased Strecker aldehydes, compared to thermo-oxidation. Based on discriminant analysis of headspace volatiles of potato chips, Maillard reaction at the final stage (heterocycles formation) is hypothetically became less intense with increasing PEF energy for Crop-77, depended on PEF energy for Moonlight and Nadine, and became more intense for Russet Burbank. Strecker degradation is hypothetically became less intense after PEF for Crop-77, depended on PEF energy for Moonlight and Nadine, and became less intense for Russet Burbank. Oxidative degradation is hypothetically depended on PEF energy for Crop-77, became more intense for Moonlight, Russet Burbank, and Nadine. Moreover, the effect of PEF (electric fields of 0.5, 0.7, 0.9, 1.1 kV/cm; 20 µs pulse width; 100 Hz and specific energy inputs of 50 and 150 kJ/kg) on the properties of potato starch was investigated on Agria potato. This study has shown that PEF had no effect on the native state of starch granules inside potato tissue as indicated by the presence of birefringence properties of starch after PEF treatment. The thermal stability, gelatinisation behaviour, susceptibility of starch in potato to hydrolysis by heat-stable α-amylase and digestive enzymes under in vitro human digestion conditions remained unchanged after PEF treatment. However, starch on the surface of potato that leached out into the medium was found to be more prone to PEF treatment effects, especially after treatment with high energy of PEF, as indicated by a narrow range of the gelatinisation temperature. The impact of PEF on colour development and formation of volatile compounds through Maillard reaction and during frying of potato chips was shown in this study to be cultivar dependent. As hypothesised, potato cultivars having distinct different chemical properties responded differently to PEF when processed into potato chips. Concerning both colour and volatile parameters, the frying performance of potato cultivar was influenced by PEF when the glucose content was relatively low (as found in Crop-77 and Russet Burbank). Crop-77, a cultivar having a distinct low in glucose/amino acids ratio showed decreased levels of alkylpyrazines with increasing PEF, while Russet Burbank, a cultivar having a moderate glucose/amino acids ratio showed lowered activation energies of frying with increasing PEF. However, the impact of PEF on the colour and volatile profiles was not affected by decrease in glucose content due to leaching. Probably, changes in amino acids was more influential in determining the effect of PEF on the colour and volatile profiles of the potato cultivars. Lastly, this study shows that PEF treatment does not influence the properties of starch found in potatoes. Based on this study, strategic selection of potato cultivar and optimisation of PEF processing parameters are possible and essential to achieve optimal benefits of retained starch properties, improved colour, and reduced levels of acrylamide-precursors in potato chips

    Assessing the translational potential of oxytocin receptor blockade as a novel therapy for cardiac sympathetic activation following acute myocardial infarction

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    Abnormal elevation of cardiac sympathetic nerve activity (cSNA) is a major contributor to the high mortality rate associated with acute myocardial infarction (MI). Increase in cSNA results in the propagation of ventricular arrhythmias, worsening the severity of damage to the heart and increasing the risk of sudden death. It was recently discovered that immediate administration of oxytocin receptor blockers (OTB) after a MI prevented increases in cSNA and improved survival outcomes. However, it is unknown whether the efficacy of OTBs would be maintained if administered at a later stage when cSNA would already be elevated. Thus, the purpose of this study was to investigate whether delayed administration of OTBs would allow for the reversal of elevated cSNA back to normal pre-infarct levels. CSNA was recorded pre- and post-infarct for four hours using surgical and in vivo electrophysiological techniques on 22 urethane-anesthetised rats. In vivo surgical procedures were conducted in order to obtain haemodynamic and electrophysiological data. A MI was induced via physical ligation of the left anterior descending coronary artery. One hour post-infarct, a proportion of MI rats were treated with Atosiban (ATB), an OTB, to determine if there were any alterations to cSNA levels when compared to an untreated MI. CSNA was also recorded in sham rats without inducing a MI. All rats treated with ATB (n=6) survived throughout the four hour recording, compared to the 50% survival rate of untreated MI rats (n=10). As expected, MI rats exhibited increases in cSNA, with a significant difference from the sham group occurring from 120 minutes (34 ± 11%, P = 0.0417) onwards. However, the cSNA levels of ATB treated rats did not present any significant decreases and continued to increase over time, following a similar trend to the untreated MI group. These findings suggest that delayed administration of ATB may not significantly reduce elevated cSNA levels, but could possibly lessen the overall increase in cSNA over time. Further investigation is needed to determine whether or not OTBs can be used as a therapeutic strategy in treating acute MI

    Ecological restoration and environmental philosophy: International visitor experiences at Aotearoa (New Zealand) eco-sanctuaries

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    Ecological restoration projects have been developed in various regions in Aotearoa (New Zealand) to address biodiversity loss and to provide human-assisted recovery of damaged, destroyed and degraded ecosystems. While the success of the ecological restoration is primarily assessed in terms of the science of ecology, it is also dependent on sustained social and economic support. Human values and action profoundly shape the implementation and success of ecological restoration projects. Societal discourses relating to ecological restoration are important to an extent that demands rigorous social science insights. Tourism provides biodiversity conservation and ecological restoration with both economic justification and opportunities arising from human-nature experiences. Nevertheless, the intersection of ecological restoration and the social sciences is largely overlooked in rigorous academic studies. In Aotearoa, a number of eco-sanctuaries have set out to develop tourism to financially support their primary function of ecological restoration. The development of these projects is mainly in response to New Zealand’s biodiversity crisis which has been historically driven by the ravages of introduced alien (exotic) species. Accordingly, eco-sanctuaries are predominantly characterized by intensive eradication and control of invasive alien species, and the translocation and breeding of endangered native species. These aspects of ecological intervention and management raise a number of complex moral and ethical issues that are poorly understood. Although tourism is argued to bring both opportunities and challenges to the development of eco-sanctuaries, little is known about eco-sanctuary visitors and their experiences at these sites. This thesis examines social perceptions of ecological restoration and considers their implications for visitor experiences in mainland eco-sanctuaries. The thesis focuses on international visitors and eco-sanctuary stakeholders, employing theories of environmental philosophy, including environmental ethics and aesthetics, in order to achieve in-depth insights into how aspects of ecological restoration are perceived and understood by different actors. Guided by social constructionism, the thesis uses a case study approach at three mainland eco-sanctuaries, using qualitative methods including photo-elicitation and flash interviews, combined with a comprehensive programme of semi-structured interviews. The thesis provides empirical evidence of the multiple meanings of ecological restoration by international visitors. It finds that international visitor perceptions of ecological restoration reflect disparate biodiversity interpretations and contrasting conservation narratives which inform potentially polarising visitor experiences at New Zealand eco-sanctuaries. At a deeper level, the thesis uncovers the critical roles of environmental ethics and knowledge and awareness in shaping distinct individual perceptions of ecological restoration. These perceptions cast light upon sharp distinctions and subtle nuances between the eco-sanctuary experiences among international visitors. The thesis also reveals a wide range of perceptions of ecological restoration and tourism held by eco-sanctuary stakeholders. Informed by these insights, the philosophies of eco-sanctuary stakeholders can either challenge visitors to reflect upon their ecological perspectives or pay increased attention to visitor interests and accommodate diverse perspectives in the provision of the tourist experience. The different philosophies of eco-sanctuary stakeholders may offer valuable insights into the co-creation of diverse international visitor experiences at New Zealand eco-sanctuaries. Through addressing several significant gaps in the existing literature, the thesis responds to calls to advance the social sciences of ecological restoration through the development of relevant tourism knowledge. Furthermore, it complements and extends current research on environmental and conservation narratives in Aotearoa by highlighting contrasting tourist narratives. The thesis empirically advances the transdisciplinary agenda of tourism and environmental philosophy by adding new understandings of environmental ethics and aesthetics on both the supply and demand sides of tourism. Two empirically informed conceptual frameworks are presented and discussed to cast light upon (co-created) visitor experiences that are produced by key actors and consumed by international visitors at mainland eco-sanctuaries in Aotearoa. Given that ecological restoration projects and tourism have been increasingly connected at a global scale, the thesis also provides valuable information for international audiences through building emerging theory which clarifies the relationship between international visitor experiences and perceptions of ecological restoration

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