13,101 results for Doctoral

  • Effect of sodium hypochlorite and Tooth Mousse™ on hypomineralised enamel in Molar Incisor Hypomineralisation

    Batra, Anuj (2011)

    Doctoral thesis
    University of Otago

    Although Molar Incisor Hypomineralisation (MIH) is being investigated in various parts of the world but our understanding of this entity is still quite limited. The hypomineralised enamel in MIH is weaker than normal enamel and may present with white chalky spots, yellow or brown areas. The surface may be rough with missing enamel due to post-eruptive breakdown. Teeth affected by MIH may be sensitive to cold air and foods, and mechanical stimuli like tooth brushing. Children avoid brushing the affected teeth leading to plaque accumulation which may make these teeth more susceptible to dental caries. Post-eruptive enamel breakdown also contributes to dentine exposure with increasing severity of sensitivity (Weerheijm et al, 2001a). In addition, management strategies for treating teeth affected by MIH are limited with a high failure rate of restorations. As a result of issues of sensitivity and poor long term success rate of restorations many MIH molar teeth are extracted. Saroglu et al (2006) and Venezie et al (1994) have recommended the use of sodium hypochlorite (NaOCl) to remove proteins from enamel in order to improve bonding. However, this was based on case reports without any scientific evidence of the efficacy of this pre-treatment with NaOCl. The remineralisation potential of Tooth Mousse™ (Casein Phosphopeptide-Amorphous Calcium Phosphate) has been investigated in dental caries but its efficacy in altering hypomineralised enamel has only been investigated in one study (Baroni et al, 2011). The objective of this research was to investigate the potential improvement in mechanical properties of Molar Incisor Hypomineralisation (MIH) enamel following application of Tooth Mousse™ with and without pre-treatment with NaOCl. It was hypothesised that NaOCl might remove some of the excessive organic content from MIH enamel which might improve the uptake of minerals by hypomineralised enamel. Brief study outline: Seven extracted first permanent molar teeth affected by MIH were collected from different dental practitioners around New Zealand after ethics approval from the Multi-region ethics committee. These teeth were sectioned and a total of twelve samples were obtained. All samples were subjected to three tests; laser fluorescence (LF), nanoindentation (NI) and confocal microscopy (CM). This was followed by division into four groups: Group I: Sodium hypochlorite (NaOCl) pre-treatment group Group II: Sodium hypochlorite (NaOCl) and Tooth Mousse™ treatment group Group III: No treatment group Group IV: Tooth Mousse™ treatment group The NaOCl (5 percent NaOCl for 5 minutes) pre-treatment was done in the first two groups followed by LF, NI and CM tests. All the samples were then stored for 30 days following which LF, NI and CM were repeated. The Tooth Mousse™ application was done daily and the Hank‟s solution was replenished every day. The results of this in vitro study showed based on nanoindentation and laser fluorescence that surface organic was removed from hypomineralised enamel following a single application of five percent NaOCl for five minutes. This resulted in reduction of mechanical properties of hypomineralised enamel as shown by nanoindentation testing (surface H and E reduction of upto 41% and 30% respectively). Confocal microscopy showed mixed results after NaOCl use; protein content appeared to be slightly increased after NaOCl pre-treatment in Group I whereas it was decreased in Group II. Daily application of Tooth Mousse™ for thirty days and storage in Hank‟s solution without prior NaOCl pre-treatment improved the mechanical properties of hypomineralised enamel (surface H and E improved by 258% and 226% respectively). Storing the hypomineralised teeth in Hank‟s solution also resulted in improved mechanical properties of enamel (surface H and E increased by 49% and 34% respectively). Therefore, it is not clear how much improvement in mechanical properties of hypomineralised enamel was due to Tooth Mousse™ alone. In conclusion, further investigation is needed to study the longer term effects of Tooth Mousse™ in MIH. This would be improved by investigating the enamel in an in situ design study. Also, future investigations should aim at a larger sample size as the present study only involved three samples in each group.

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  • Perceptions of Relational Aggression among New Zealand Adolescent Girls and their Classroom Teachers: The Popular, the Regular, and the Tough Girls

    Page, Angela (2011)

    Doctoral thesis
    University of Otago

    Relational aggression concerns behaviours intended to harm someone by damaging or manipulating relationships or feelings of acceptance, friendship, or group inclusion (Crick & Grotpeter, 1995). The purpose of this study was to identify perceptions of relational aggression of Year 9 and 10 girls (N = 282) in New Zealand, compare views of teachers and adolescent girls with regard to relational aggression in the classroom, and explore strategies to effectively manage relational aggression in the classroom. To achieve this goal, The Personal Experience Questionnaire (PEQ) and Relational and Physical Aggression Scenarios, revised with permission (Basow, Cahill, Phelan, Longshore, & McGillicuddy-DeLisi, 2007), were used to determine girls’ perceptions of relational aggression. Subsequent to the surveys, semi-structured interviews were conducted with n = 15 girls and their classroom teachers (n = 15) to provide a deeper understanding of relational aggression and the strategies considered important to address it. Findings indicated that overall, the types of relational aggression that occur among girls in Year 9 and Year 10 schools in New Zealand involved more indirect than direct behaviours. However, the most prevalent behaviour was direct verbal aggression (yelling at or calling another mean names, and direct verbal put-downs). Text bullying did not play a major role in relational aggression in class. Differences and similarities of the perceptions of teachers and girls of relational aggression in the classroom are reported. PEQ results showed that all participants were more likely to view others as engaging in non-aggressive relational aggression more than themselves. Similarly, girls were more likely during the interviews to report on other girls’ relationally aggressive behaviours rather than their own. Year 10 girls reported showing and receiving more prosocial behaviour than did the Year 9 girls; the Year 9 girls reported perpetrating more relationally aggressive behaviour. Relationally aggressive scenarios were perceived by the girls as significantly more acceptable, but more distressing, than the physically aggressive scenarios. Differences in year level were significant in that Year 9 girls reported a greater tolerance and lower level of hurt from physical aggression than Year 10 girls. Significant correlations were also found between the PEQ Self and Others scores and the scenarios, indicating differences in perception between how girls view themselves compared to others. A strong relationship between PEQ Self and Other scores for relational and physical aggression indicated that girls viewed outcomes of physical and relational aggression similarly, differing from reports with the scenarios. Strategies described to effectively collaborate in efforts that prevent and/or manage incidences of relational aggression in the classroom indicated that talking to a supportive adult was found to be best strategy by both girls and their teachers. From the study, three types of aggressors emerged: Popular, Regular, and Tough girls. These are presented in a proposed model that describes each type. The model is then applied to examine how teachers use different behaviour management strategies depending upon the behaviour and type of student perpetrating relational aggression in their classroom. The results of this research may provide help for adolescent girls to develop ways forward for building healthy relationships.

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  • Influence of preparative techniques on the structure, stability and dissolution of amorphous drugs

    Karmwar, Pranav (2011)

    Doctoral thesis
    University of Otago

    Poorly soluble drugs are becoming increasingly common in the pharmaceutical setting. Such drugs often exhibit dissolution rate-limited absorption and therefore methods to increase the dissolution rate of such drugs are of considerable interest. One promising strategy to increase the dissolution rate is to prepare the drug in an amorphous form. However, since the amorphous form is thermodynamically unstable, it may crystallise at any stage of the "life cycle" of the pharmaceutical formulation, including during manufacturing, storage and administration, with the result being a loss of the increased dissolution rate. The stability of amorphous forms depends on a variety of factors such as thermal, structural, thermodynamic and kinetic properties of the compound in addition to preparation techniques, processing parameters and storage conditions. Amorphous drugs prepared by different preparative techniques and different processing parameters may exhibit different crystallisation behaviour or solid-state transformations during storage and dissolution. In this work, indomethacin is made amorphous using different preparative techniques such as melting, milling and spray-drying. Firstly, the amorphous drugs were prepared by the different methods and processing parameters and were characterised by x-ray powder diffraction, differential scanning calorimetry and spectroscopic methods. Secondly, the theoretical stability (based on thermodynamic equations) was correlated with the experimental stability. Furthermore, intrinsic dissolution studies of the prepared amorphous solids were performed. In addition in this study the interpretation of analytical data, and especially spectroscopic data was supported by the use of multivariate data analysis methods. In Chapter 2, the amorphous samples prepared by different preparative techniques were investigated and structural and thermal differences due to preparative techniques were revealed. The ranking of the samples with respect to stability was: quench cooled amorphous samples > cryo-milled (α-form) > spray dried > ball milled (α-form) > ball milled (γ-form) = cryo-milled (γ-form). While structural differences, identified using Raman spectroscopy (using multivariate analysis), did not appear to directly correlate with the physical stability ranking. The relaxation times, calculated by using the Adam Gibbs and Kohlrausch–Williams–Watts equations however were in accordance with the experimentally determined stability rank order. This study showed that correlation of physical stability with calculated relaxation time is possible for the amorphous forms of a single compound. In Chapter 3, pair-wise distribution function (PDF) analysis was performed on samples of indomethacin obtained by cryogenic ball milling (cryo-milling) for different periods of time to detect the extent of disorder induced. Using PDF analysis it was possible to determine the optimal cryo-milling time that facilitated the highest degree of disorder in the samples. In Chapter 4, the effect of cooling rate on the physicochemical properties of the resulting amorphous solids prepared from the melt was investigated. It was revealed that the minimum cooling rate required to obtain amorphous indomethacin was 1.2 K min-1, as assessed from the time-temperature-transformation diagram. The stability of the samples was found to increase as a function of cooling rate and was in agreement with descriptors for the glass forming ability and the kinetic exponent M from the autocatalytic Sestak-Berggren model. In Chapter 5, intrinsic dissolution studies were carried out for the amorphous solids prepared in Chapters 2 - 4. The samples cooled at different cooling rates showed no significant differences in their dissolution profiles and dissolution rates. In contrast, the dissolution rate of the cryo-milled samples depended on the milling time. The milling process appeared to continue to affect the degree of disorder in the solid material, enhancing its dissolution rate. It can be concluded that amorphous solids prepared by different preparative techniques and different processing parameters have different structural and thermal properties. These differences affect the physical stability and dissolution profiles of the amorphous solids. Some predictive relationships between the preparation and performance characteristics have been determined, which can support the development of optimised formulations containing amorphous drugs.

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  • Vernalization response in Medicago truncatula

    Jaudal, Mauren Cali (2011)

    Doctoral thesis
    University of Otago

    Vernalization is the acquisition of the competence to flower upon exposure to prolonged winter cold. The physical conditions that promote vernalization have been analyzed here in the model legume, Medicago truncatula. The length of cold treatment correlates with the promotion of floral transition. Vernalization is optimum within the 4C- 10C range for two weeks and tends to saturate at longer duration. Whole plants are equally responsive to vernalization treatment as imbibed seeds. FT is a key flowering time gene that has been shown in a range of plants to encode a floral signal molecule that is produced in the leaves and moves to the apex to induce flowering. There are five copies of FT-like genes in Medicago (MtFTLa-e), but only MtFTLa, MtFTLb, and MtFTLc were shown to be upregulated by vernalization. Among the MtFTLs, MtFTLa has been shown to be the major flowering time gene whose expression is regulated both by long-day (LD) photoperiod and vernalization. The duration of cold has a quantitative effect on MtFTLa expression and induction of flowering. However, vernalization-induced upregulation of MtFTLa does not occur right after the prolonged cold treatment but takes place after growth in LD photoperiods. This finding and the observation that MtFTLa is expressed only in leaves that expanded after vernalization but not in differentiated ones present prior to the treatment, suggest that vernalization is an epigenetic process that requires dividing or undifferentiated cells. Further analysis of the MtFTLa locus using chromatin immunoprecipitation techniques revealed that the epigenetic regulation of MtFTLa expression is indeed associated with changes in chromatin modification. High transcript levels of MtFTLa following vernalization are consistent with enrichment of the H3Ac mark and concurrent loss of the H3K27me3 at part of the promoter (promoter B) of MtFTLa, modifications that are linked with chromatin structure permissive for transcription. Changes in histone marks were also observed at the more distal promoter region (promoter A) of MtFTLa. To identify components that might be involved in vernalization response, sequences homologous to the PHD-finger containing VIN3 and the MADS-box genes AGL19, AGL24, and SVP were identified in Medicago. Although, MtVIN3 has relatively conserved PHD and VID domains typical of the VIN3/VEL family, unlike in Arabidopsis, its expression was not significantly induced by vernalization. Ectopic expression of MtVIN3 in Arabidopsis did not alter the flowering time. MtAGL19, MtAGL24, MtSVP1 and MtSVP2 are highly-expressed in apical buds and leaves during the vegetative stage of development but minimally detected in floral organs. These MADS-box genes are not responsive to vernalization, which is expected for MtSVPs. The flowering time of Arabidopsis was not hastened by the ectopic expression of either MtAGL19 or MtAGL24. However, 35S:MtAGL24 plants exhibited floral abnormalities that phenocopy 35S:AtAGL24 plants, such as enlarged sepals, elongated carpel, greenish/leaf-like petals, stunted siliques, and delayed maturation rate and senescence of siliques. Overexpression of both MtSVP1 and MtSVP2 genes in Arabidopsis delayed flowering with accompanying floral defects including alterations in floral organ number and symmetry, elongated carpel, larger sepals and pale green petals. The severity of the floral defects also correlated with the delay in flowering time. Apical bud genes regulated by short term cold and by vernalization treatment were identified using Affymetrix GeneChip Medicago Genome Arrays. The microarray data showed that the “cold-shock” transcriptome of Medicago resembles that of Arabidopsis, which mainly involves genes implicated in the cold-acclimation pathway and putative transcription factors (TFs). Among the genes stably upregulated by prolonged cold include three genes with predicted chromatin-related functions and one uncharacterized gene annotated as “cold-responsive”. There are significantly more genes downregulated than upregulated by prolonged cold in apical buds, among of which encode products homologous to the chromatin modifier SNF-2, a FYVE/PHD zinc finger-containing protein, and a putative novel TF with annotated transcriptional repressor activity. Analysis of the leaf microarray data also showed that among the genes stably upregulated by prolonged cold treatment following growth in LD photoperiod, MtFTLa exhibited the highest fold change in expression level, consistent with its important role in vernalization response.

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  • The Straight Mind in Corinth: Queer Readings Across 1 Cor 11.2-16

    Townsley, Gillian Marie (2011)

    Doctoral thesis
    University of Otago

    Despite the lack of both historical and exegetical clarity that has emerged from scholarly study of 1 Cor 11.2-16, this passage has often been fundamental to understandings of gender and sexuality in many Christian traditions. Although both hierarchical and egalitarian models of gender have been supported by this text, with regard to sexuality there is almost always an assumption of heteronormativity. Within Christian traditions these models are often presented as “natural” and “God-ordained,” yet they are in fact profoundly political as they are viewed as foundational to notions of identity and thus determinative for power relations at individual through to societal levels. Because misogyny and homophobia are still present in Western societies, an androcentric heteropatriarchal model of gender and sexuality tends to dominate. That 1 Cor 11.2-16 can be read as supporting such a model highlights the importance of examining the sex-gender ideologies as well as the politics and power relations that lie behind both the text itself and various interpretations of it. This thesis engages queer theory in order to enable such a critical examination. Queer theory reveals models of gender and sexuality as ideological constructs but goes further than this and challenges these models by both exposing the instabilities of the supposedly normal model and presenting alternative models of gendered and sexed being. This thesis therefore intersects various biblical, theological and queer lines of inquiry across 1 Cor 11.2-16 in order to trouble the androcentric heteropatriarchal norm that has dominated this field. Accordingly, the materialist lesbian theory of Monique Wittig provides the theoretical basis for discussion in this thesis. Unlike many previous studies on this passage that focus on the “problematic women” of Corinth, Wittig’s challenge to both “particularise the masculine” and “lesbianize the men” means that the Corinthian men come under scrutiny in the first part of this thesis. The possibility that Paul is addressing the behaviour of the men in this passage and the suggestion that he is dealing with “a horror of homosexualism” reveals that inadequate attention has been given to the ways in which ideology influences biblical studies and also to the range of differences between the first and twenty-first century understandings of sex, gender and sexuality. Wittig also challenges us to “attack the order of heterosexuality in the texts” and to “produce a political transformation of the key concepts.” Therefore, the second half of this thesis explores three key terms from 1 Cor 11.2-16, namely kephale (“head”), the imago dei and fusis (“nature”). A diverse range of material is examined, including the primary evangelical groups that debate the meaning of kephale (“head”), Karl Barth’s theology on “Man and Woman” and the imago dei, and Robert Gagnon’s work The Bible and Homosexual Practice. By critically investigating these in light of Wittig’s theories, the androcentric heteropatriarchal systems of thought that Wittig calls “the straight mind” are both revealed and challenged. With regard to Gagnon, in Chapter Six Wittig’s fictional work The Lesbian Body even physically forces his work to disappear altogether through the inter-play of columns on the page. Rather than continuing the debates on the various exegetical and historical issues that occupy much of the scholarship on this passage, this thesis shifts the discussion of 1 Cor 11.2-16 into what Stephen Moore describes as “a radically different register” – traversing, troubling and transgressing the normal – and ultimately affirms Wittig’s proposal that, “a new personal and subjective definition for all humankind can only be found beyond the categories of sex (woman and man).”

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  • Pacific participation in Aotearoa/Niu Sila Netball: Body image, family, church, culture, education and physical education.

    Schaaf, Rosaline Michelle Joyce (2011)

    Doctoral thesis
    University of Otago

    This thesis explores the netball experiences of a selection of people residing in Aotearoa/Niu Sila who have participated or continued to participate in netball. Adopting an inter-disciplinary approach, it sheds a light on the broader socio-cultural and political factors that have influenced and shaped Pacific women’s experiences of netball. In particular, this research investigates how Pacific women negotiate and grapple with the following aspects of their lived experiences: family, church, culture, education, physical education, sport and body image in relation to their participation in the sport of netball. The information for this study was gleaned from primary and secondary sources and in-depth interviews with 18 current and former netball participants. Case studies of media representation of the body shape alongside the participants’ voices were utilised to illustrate the ways Pacific women have begun to mirror Western norms for beauty, the contingent nature of normative body ideals, and the ways non-normative bodies are regarded as ‘projects of remediation and the minimal currency that strong muscular women’s bodies’ hold within a Western aesthetic. The participants’ words have been integrated throughout from Chapter Four onwards because I wanted to move away from the traditional literature review, method, results, and discussion structure. As a result, the participants’ testimonies have been brought alongside current literature, as opposed to being used as a ‘results to add’ to current literature in a positivistic sense. Exploring Pacific women’s netball experiences in relation to family, church, culture, education, physical education, sport and body image, provides unique insights into the nature and dynamics of netball in Aotearoa/Niu Sila, shifting social constructions of femininity and Pacific women’s sporting identities, as well as Pacific women’s unique and diverse experiences and understandings of their participation.

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  • Chronic Kidney Disease and its Clinical Implications on Red Blood Cell Survival and Glycaemic Control

    Vos, Frederiek Eva (2011)

    Doctoral thesis
    University of Otago

    World-wide the incidence of individuals developing stage 3 to stage 5 chronic kidney disease (CKD) is increasing. Diabetic nephropathy is the major aetiological factor for this increasing epidemic of CKD. A significant complication of CKD is the development of a normochromic normocytic anaemia related to a lack of erythropoietin as well as possible erythropoietin resistance along with a reported decrease in red blood cell (RBC) survival. The altered RBC survival may affect the validity of glycated haemoglobin (HbA1c) which is used as the standard assessment of glycaemic control in long term diabetes management. The uraemic environment of stage 4 and 5 CKD and potentially the dialysis procedure itself may contribute to altered RBC survival. At present, there is inconsistent data and little agreement to what extent the RBC survival is reduced in the setting of CKD, particularly now with the availability of erythropoietin stimulating agents (ESAs) and modern dialysis techniques. Additionally, it is unclear what impact ESAs, now used in the majority of dialysis patients, have on the accuracy of HbA1c. Normal RBC survival is considered to be 120 days, however this value was based on very few data using methods that were inadequate and is for this reason debatable. The available methods to study RBC survival are all limited in their applicability, and no ideal technique exists. Labelling with radioactive chromium (51Cr), currently deemed the gold standard for measuring RBC survival, is limited by unavoidable losses of label from RBCs. When using the 51Cr method, it is necessary to incorporate factors to account for these inevitable losses. However, these losses have not been systematically investigated. The first part of this thesis was to examine the accuracy of current methods of assessing RBC survival both in vitro and in vivo. Prior to conducting in vivo RBC survival studies, the different pathways of 51Cr loss were explored. To identify and evaluate the unavoidable losses occurring from intact RBCs, blood of healthy and CKD subjects was labelled with 51Cr and disappearance of label was studied under in vitro conditions. Elution and vesiculation were identified as mechanisms of label loss, and are independent of RBC destruction. The major pathway of loss was elution and vesiculation accounted only for minor amounts, further quantification was restricted by the in vitro design of the study. To determine whether RBC survival is reduced in dialysis patients and differs among dialysis modalities, survival was determined by means of the 51Cr labelling. Relative RBC survivals were measured in haemodialysis (HD) and peritoneal dialysis (PD) patients and compared to healthy subjects. The RBC survival was demonstrated to be significant shortened in dialysis patients when compared to healthy controls, though the observed relative reduction was less than previously stated, it remains to contribute to the anaemia of CKD. Similar RBC survivals were noted in HD and PD patients. The second part of the thesis examined the impact of decreased RBC survival on the accuracy of glycated haemoglobin (HbA1c) as a marker of glycaemic control in diabetic patients with stage 4 and 5 CKD compared to other assessments of glycaemic control including glycated albumin, fructosamine and continuous glucose monitoring. In CKD, the alterations in RBC turnover, due to reduced cell survival and/or ESA administration, have an impact on the HbA1c concentration and thereby likely reduce its accuracy. The exact relationship between different markers of long-term glycaemic control and real-time glucose needed to be established. The reliability of HbA1c was investigated in a population with diabetes and severe CKD (CKD stages 4 and 5: glomerular filtration rate < 30 mL/min) by means of continuous glucose monitoring and compared to other markers of glycaemic control, namely glycated albumin (GA) and fructosamine. Average glucose concentrations were underestimated by HbA1c concentrations in diabetic subjects with CKD stages 4 and 5. It was demonstrated that GA was more accurate in reflecting average glucose in predialysis and dialysis patients and should be the preferred marker in the assessment of long-term glycaemic control in this population. The final aspect of the thesis arose from an interest in the role of insulin as an anti-inflammatory agent and what impact a continuous insulin infusion during a haemodialysis session might have on markers of inflammation which are known to be elevated in haemodialysis patients. The risk of cardiovascular morbidity and mortality is substantially increased in the dialysis population. Haemodialysis is associated with a pro-inflammatory state and increased oxidative stress which contributes to the increased risk of cardiovascular disease in CKD. Insulin has been demonstrated to exhibit anti-inflammatory actions. A pilot study was undertaken to explore if an insulin infusion during haemodialysis modifies markers of inflammation and oxidative stress. Anti-inflammatory effects of insulin were demonstrated by a reduction of CRP in the immediate 24 hours following a standard dialysis accompanied by an insulin infusion. Further exploration of the relevance of this finding is required.

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  • Surgical trainee decision making: Exploring, modelling, teaching and learning

    Rennie, Sarah Catherine (2011)

    Doctoral thesis
    University of Otago

    Decision making is a key competency for surgeons and trainees; however, neither its key components, nor how it should be taught and assessed, are well understood in all surgical settings. Most surgical decision making research has investigated elements of decision making in elective, pre- and intra-operative settings. This thesis explores trainee surgical decision making in the acute setting, focusing on less controlled settings of the ward and emergency room. Using qualitative structured interviews found that trainees primarily described using naturalistic methods in contrast to previous hypotheses. They predominantly utilised pattern recognition, with patient appearance being one of their main cues. In contrast to descriptions of expert decision makers, they did not act quickly on their decisions, consider absent cues, or trial their decision with mental simulation. Trainees described many factors influencing decision making, indicating its complexity. From this a “surgical trainee decision making mind map” was developed. Criteria that defined good and poor decisions, decision makers and essential factors for developing decision making skills were developed from a qualitative survey of international experts in surgery, cognitive research and medical education. From this the following definition of a good decision maker was compiled. A good surgical decision maker is a surgeon or trainee who makes well informed and considered, timely, patient focused decisions which are backed by a sound knowledge and good evidence-base, while recognising their own limitations, the need for collaboration, reflection and clear communication to bring about an appropriate action. The “Global Surgical Decision Making Model” was created to assist conceptualisation of acute surgical decision making and compared to current decision models. The model was also validated. A surgical decision making (SDM) eLearning package was constructed to facilitate understanding and acquisition of SDM skills. This was presented to surgical trainees and medical students for evaluation, and to assess whether medical students could act as a surrogate for the trainees. The SDM eLearning package used the “Global Surgical Decision Making Model” as a framework. Evaluation of the SDM eLearning package contributed to validation of the model, achieved learning gains in understanding of SDM, and was well received by participants. A summary of the key findings of this thesis offering interpretation and implications of the main results, and recommendations for how research can be progressed in the future has been compiled. This thesis adds to the body of surgical decision making research by: • detailing surgical trainee decision making in the acute surgical setting; • illustrating the complexity of acute trainee decisions in the “surgical trainee decision making mind map”; • identifying criteria for distinguishing good and poor decision making and decision makers, and offering a definition of a good decision maker; • detailing factors that facilitate the development of decision making skills; • providing a new model to act as a framework for considering decision making as it applies to surgical trainees; • contributing a SDM eLearning package that can be incorporated into surgical decision making curricula for both surgical trainees and medical students.

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  • Effects of Folic Acid Supplementation on Human Leukocyte DNA Methylation and Gene Expression

    Elworthy, James Mark Anthony (2011)

    Doctoral thesis
    University of Otago

    Folic acid and natural folates are B group vitamins obtained exclusively from the diet. Biochemically, folate derivatives participate in the transfer of single carbon units, acting as methyl group donors for numerous cellular processes, including the addition of methyl moieties to genomic CpG dinucleotides, a process termed DNA methylation. This is an important epigenetic mechanism that contributes to the control of gene expression and maintenance of genomic integrity. Low folate intake can result in hypomethylation of DNA, which can disrupt gene expression and promote genetic instability. Genomic hypomethylation is associated with the progression of numerous diseases, including multiple cancers and atherosclerosis. Conversely, limited evidence suggests excessive folate intake may also enhance development of certain carcinomas. The enzyme methylenetetrahydrofolate reductase (MTHFR) commits folate-bound one-carbon moieties to the DNA methylation pathway. A common enzyme variant of reduced catalytic function may modify the relationship between dietary folate intake, DNA methylation and disease propensity. However, there is a paucity of studies in humans that wholly link these events. Additionally, New Zealand is considering introducing mandatory folic acid fortification to reduce the incidence of neural tube defects. Accordingly, the current study sought to assess changes in DNA methylation as a result of modulated folate intakes in a normal, healthy New Zealand population, which might infer a propensity towards disease. Peripheral blood was obtained from 93 participants (equally matched by number, age and sex across all MTHFR genotypes) following a thirteen week folic acid avoidance period and a subsequent eleven week folic acid supplementation period (400 µg folic acid/day). Mean plasma folate fell across all MTHFR genotypes by 7 nmol/L (p < 0.001) and increased by 26 nmol/L (p < 0.001) following folic acid avoidance and supplementation, respectively. Total homocysteine, an inverse and intermediate indicator between folate status and DNA methylation, decreased significantly following supplementation (p < 0.001). This was most pronounced in individuals homozygous for the MTHFR polymorphism with a low folate status (< 12 nmol/L) during the avoidance period. Despite global hypomethylation being observed under similar conditions by other researchers, no significant change in leukocyte DNA total methylation was found in the current study, either between MTHFR genotypes, or between folate avoidance and supplementation periods. This was measured using high performance liquid chromatography and mass spectrometry methods. Microarray analysis of leukocyte-derived RNA revealed a small number of genes differentially expressed between genotypes and dietary regimes; however fold change was slight and follow-up analysis indicated none were probable disease candidates. The methylation status of repetitive satellite 2 elements was queried using a methylation-sensitive restriction digest followed by quantitative PCR. Participants homozygous for the MTHFR polymorphism displayed a small but significantly lower level of Sat2 methylation. This difference was not observed following supplementation. These results suggested a negligible DNA methylation response to modulated folate status and no indication of disease propensity – DNA methylation is particularly immune from medium term perturbations to folate intake in healthy New Zealanders.

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  • Developing and Preserving Wellbeing at the Frontline of New Zealand Police

    Gavigan, Kathleen Mary (2011)

    Doctoral thesis
    University of Otago

    New Zealand’s health and safety legislation now requires employers to manage exposure to hazards that result in stress and fatigue. Although policing is defined as a high stress occupation, due to the dangerous and unpleasant nature of the work, prevalence rates for posttraumatic stress disorder are generally low. Nevertheless, there is a need to identify hazards, as there is no consensus on police-specific hazards and their management. There is also a lack of research on the aspects of the police work environment that promote wellbeing. Thus, this research asks what keeps officers well, what aspects of police work might adversely affect officers and how might exposure to psychosocial hazards be managed? Its focus is on frontline police officers’ experiences of police work and their conditions of deployment. Grounded Theory is used to reach an understanding of officers’ perceptions and interpretations of their work as well as the conditions of variation and how these are associated with the outcomes of exposure. Unstructured, in-depth interviews were conducted with sixty-one officers across a range of police roles and two field observations were undertaken. Incidents in the data were analysed using the constant comparison method and processes, conditions and consequences of exposure were identified, in relation to both wellbeing and adverse effects. Dealing with death, victims of violent crime, confrontation and criticism, work overload and unsupportive aspects of the work environment are areas of concern for officers. Exploring and analysing these issues led to the development of a dynamic and interactive model that relates emotional reactivity to learning from experience. Through the interacting processes of habituation and sensitisation, officers develop knowledge and expectancies that enable automatic responding, a task focus and perspective taking. Organisational structures, systems, practices and niches that enable a fit within the organisation, are all essential to developing means of control. Thus, officers acquire mastery of problematic situations, mental barriers and a self-efficacy belief, which reduce emotional arousal, enable avoidance of adverse consequences and keep them well. However, under- or over-exposure to emotionally challenging aspects of police work, without an adequate means of control, can lead to prolonged sensitisation and an inability to re-establish habituated responding, which may adversely affect officers occupational functioning. It is argued that four conditions associated with repeated exposure need to be managed, namely empathic over-arousal, tunnel vision, inadequate recovery intervals and unresolved practice issues. Furthermore, in the absence of the organisational provision of means of control, officers act to ensure their survival in the job. While this is protective for officers, it may have unintended consequences for the police organisation and so a collaborative approach is needed to resolve persistent practice dilemmas. This research highlights the importance of conceptualising cumulative exposure to aversive situations and avoidance behaviour, as having both beneficial and adverse effects. Although emotional detachment is often viewed as an unhelpful aspect of police culture, this needs to be distinguished from emotional suppression since detachment itself appears to keep police officers well.

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  • 'We live inside a dream': Ideology and Utopia in the Films of David Lynch

    Cartwright, Garth (2011)

    Doctoral thesis
    University of Otago

    In this thesis I contribute a political reading of David Lynch’s films. To do so I employ a mode of ideological analysis that draws explicitly on the thinking of Fredric Jameson and in particular his conception of three ‘concentric interpretative horizons’: the political, social, and historical. Taking these horizons as three perspectives on David Lynch, I contend that Lynch’s films have entered into a dialogue with various processes and events inhering in our own historical moment of globalised multi-national capitalism. My Introduction surveys the terrain of existing scholarship on David Lynch, identifies the various alternative or competing modes of analysis and interpretation and enables a number of Lynch’s most notable commentators to have their say prior to setting out the terms of my own argument. Chapter one constitutes an analysis of Jameson’s thinking, particularly in relation to his conception of a ‘political unconscious’. This chapter also attempts to situate this thinking historically in relation to Marxist critical theory. Chapter Two, corresponding to Jameson’s first interpretative horizon — the political — involves an analysis of Lynch’s narratives which are discussed in relation to genres, institutions and traditions, so as to situate them in relation to contemporary and postmodern forms of cultural production. In Chapter Three I introduce the argument that Lynch’s films can, to greater or lesser degrees be seen as variants of what Jameson refers to as ‘conspiratorial texts’. In focusing on the second interpretative horizon — the social — I consider Lynch’s filmic conceptions of community. In particular I explore the inherent antagonisms pertaining between Lynch’s protagonists and their respective community’s institutions and social structures. Finally, Chapter Four is explicitly concerned with the form of Lynch’s films and corresponds to the third and final of the interpretative horizons; the historical. Here I consider Lynch’s connections with and relations to what I will call discourses of ‘non-rationalism’, most significantly Surrealism. I argue that these discourses, involving specific modes of knowledge and understanding, are set in opposition to, and possibly constitute critiques of, forms of reason and rationality primarily associated with the Enlightenment. Each of these three levels of interpretation, the political, social and historical, involves a dialectic — between form and content, subject and community, and present and future — and it is in relation to these dialectics that I situate my political interpretation of David Lynch’s films.

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  • Mandibular deformation in a partially dentate mandible with and without restoration with a fixed implant restoration

    Law, Ching-Yee Constance (2011)

    Doctoral thesis
    University of Otago

    Background:The human mandible, like all long bones in the body, deforms when loaded. The force exerted by the muscles of mastication during various movements on the body of the mandible has been suggested to play a significant role in mandibular flexure. The effect of the lateral pterygoid muscle on mandibular deformation is controversial with some authors believing that the location of insertion and action of the inferior head of the lateral pterygoid muscle contributes most to mandibular deformation during opening. Restoration of mandibular edentulous areas with implant prostheses is increasing in popularity. Osseointegrated implants behave differently to natural teeth due to the absence of a periodontal ligament, and therefore strain introduced to an implant is transmitted directly to the body of the mandible. Different stages of implant treatment, including implant placement, impression technique and the material used to fabricate the implant prosthesis can be affected by mandibular flexure and alter the outcome of implant treatment. The significance of mandibular flexure in implant dentistry, however, is unclear at this time and it is hoped that this study will contribute to knowledge in this area. Aim:To measure the extent of mandibular deformation and strain distribution within a mandible model restored with a screw-retained implant prosthesis. Methodology:Two Certain® Biomet 3i implants were placed in a partially dentate resin mandible model and four cobalt-chromium alloy implant fixed frameworks were constructed. Eight strain gauges were attached to the body of the mandible and eight adjacent to the implants. The mandible was suspended from a customized jig simulating the temporomandibular joint with elastic cords that enabled simulation of the glenoid fossa and the muscles of mastication. Using a universal testing machine, mastication was simulated to generate a unilateral 50 N force on the occlusal surface of the mandibular first molar. The strains were continuously recorded using a computer, first without the implant framework, then during and after framework tightening to 20 Ncm. Results:Under unilateral loading without the implant framework in place, the area of strain distribution was similar to that of a finite element analysis of a human mandible developed at the School of Dentistry, University of Otago. The results showed that the epoxy resin mandible model used in this study behaved similarly to a human mandible under unilateral loading. Unilateral loading of the epoxy resin mandible model with the implant framework in place showed a strain distribution on the body of the mandible model that was similar to that without implant frameworks. Each of the four frameworks showed a different pattern of peri-implant strain distribution after they were tightened to the implants. The difference in strain could be contributed by variation in casting conditions and solidification shrinkage. The strain distribution patterns at the peri-implant level more closely resembled the strain distribution after implant framework placement. Peri-implant strain was framework-specific depending on the extent of initial misfit of the individual framework. Conclusions:This study showed that mandibular flexure occurred during unilateral loading. The amount of peri-implant strain during unilateral loading before implant framework placement was within the limits that the mandible is able to repair micro-damage occurring within the body of the mandible and around the implants. Placement of misfitting implant frameworks affected the strain distribution at peri-implant level. Unilateral loading, combined with the strain generated by mandibular flexure, as well as the existing strain resulting from a misfitting implant framework, can increase the strain at peri-implant level. This amount of strain could be harmful to the peri-impant bone during cyclic loading. The clinical implications of the results of this study are unclear at this stage and further research is required.

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  • Sleep and the potential of sleep hygiene for weight management in youth

    Tan, Evan (2011)

    Doctoral thesis
    University of Otago

    The rate and prevalence of childhood obesity and its associated morbidities, such as obstructive sleep apnoea (OSA), is increasing. Sleep disruption due to OSA has been associated with neurobehavioural impairments such as less well intelligence, memory, behaviour and executive function in younger children. However, neurobehavioural studies in obese children are lacking. Thus, the first of two main studies in this thesis, the obesity study, aimed to establish a detailed description of neurobehavioural problems that can arise due to OSA occurring in obese adolescents. There is growing evidence of the relationship between short sleep duration and risk for obesity with the dysregulation of appetite hormones leptin and ghrelin thought to be a contributing factor. However, no study that we are aware of, has looked at a sleep-only intervention as a potential weight management tool in children. Thus, the second main study, the sleep study, aimed to examine the effectiveness of a sleep-hygiene-only intervention on improving sleep hygiene, sleep quality and daytime symptoms in youth. Methods and Results: In the obesity study, 31 participants aged 13.7 (SD ±2.49) years, with a mean (SD) BMI z-score of 3.0 (0.68) were classified into OSA (AHI ≥ 1) and non- OSA (AHI < 1) groups using overnight polysomnography (PSG). The mean (SD) obstructive AHI obtained for the OSA and non-OSA group was 4.69 (3.72) and 0.49 (0.32) respectively. Intelligence, memory & learning, academic achievement, behaviour and executive function were assessed using the Weschler Abbreviated Scale of Intelligence (WASI), Wide Range Assessment of Memory and Learning 2 (WRAML-2), Weschler Individual Achievement Test II (WIAT-II), Behavioural Assessment System for Children 2 (BASC-2) and Behavior Rating Inventory of Executive Function (BRIEF) respectively. Performance scores across most measures were statistically (but not clinically) significantly less well than the normative mean. There was also a non-significant tendency for the OSA group to perform less well across most measures compared to the non-OSA group. This seems to indicate possible additive impairments in obese children with OSA compared to their non-apenic but obese counterparts. In the sleep study, we first developed an age-appropriate sleep hygiene programme in consultation with children (10-18 years old) and then piloted this programme in 33 other children of the same age-group (mean age ±SD 12.9 ±2.19) and found significant improvements, 20 weeks post-intervention, in sleep hygiene as assessed by the Adolescent Sleep Hygiene Scale (0.19, CI 0.06 to 0.33; p = 0.005), sleep quality as reflected in the Pittsburgh Sleep Quality Index (-2.93, CI -3.61 to -2.24; p < 0.001) and Sleep Disturbances Scale for Children (-14.1, CI -17.1 to -11.1; p < 0.001) as well as daytime sleepiness as reflected in the Pediatric Daytime Sleepiness Scale (-5.1, CI -7.0 to -3.2; p < 0.001). A small but statistically significant decrease in BMI z-scores (-0.13, CI -0.20 to 0.05; p = 0.001) and sedentary/light energy expenditure (-27, CI -50 to -3; p = 0.025) were also observed. Conclusion: Findings from the obesity study suggest that obese children tend to perform less well on neurobehavioural assessments compared to the normative population and that there is a non-significant but consistent pattern of even less well performance in the combined obesity-OSA condition. Findings of the sleep study suggest that the sleep hygiene programme developed is effective in improving sleep hygiene and quality, but more importantly highlights the potential of sleep hygiene for weight management in youth. Indeed, a follow-up randomised controlled trial investigating the long term effects of a sleep hygiene intervention on physiological, psychological and behavioural health outcomes in obese youth has been proposed and is currently being considered.

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  • A Cognitive-Relational Approach to Leadership Studies: Finding a Middle Ground For Leadership Research

    Hunt, Tresna Jacqueline (2011)

    Doctoral thesis
    University of Otago

    This thesis uses the New Zealand Police as a case study to answer the question “how can a cognitive-relational theoretical perspective provide a middle ground between the conventional Objectivist and Subjectivist polarities within leadership research?” A cognitive-relational theoretical perspective termed Relational Script Theory is engaged to explore the epistemological space between the Objectivist and Subjectivist extremes that have dominated the leadership literature. The research question reflects talk within the leadership literature that a paradigm shift is emerging. The terms “new economic era” and “post-bureaucratic organisation” reference a move away from Objectivist, static and bureaucratic approaches to leadership towards a more Subjectivist, participatory and dynamic framing of the phenomenon. A move in this direction has significant implications for traditionally bureaucratic organisations such as the New Zealand Police. The differentiation between Objectivist/static and Subjectivist/dynamic approaches to leadership has also generated a significant level of confusion and division amongst leadership scholars. The current thesis contributes to an emerging body of literature that offers alternative, middle ground strategies for researching leadership. These middle ground strategies are important because they offer a more holistic approach for researchers, interventionists and organisational practitioners when engaging with the leadership phenomenon. Moving away from the rigidity that accompanies the Objectivist/Subjectivist binary allows both the static and dynamic qualities of leadership relationships to be seen and examined. The current research employs a mixed method design to collect data from 15 leadership relationship dyads within the New Zealand Police. The data gathering techniques have been designed to allow for collecting information in two different ways. The first, hypothesis-testing interview allows for the collection of data using the Relational Script theoretical lens. The second, exploratory interview allows for the gathering of data that is not constrained by the five hypotheses and which has more emergent properties. The results of the study illustrate the cognitive-relational features of the leadership concept by observing both the dynamic and static characteristics of the relationship. At the dynamic level, the results show how leadership partners can: a) think about their relationships in multiple ways; b) adjust their relational behaviours across changing contexts; c) respond in increasingly creative ways as they become more experienced and; d) influence one another’s constructions of the relationship. At the static level, the results show how the New Zealand Police can: a) follow a particular, pre-defined developmental trajectory in their relationships and; b) desire the same qualities in their relationships across role-related groups. Two different theoretical concepts are extracted from the results including The Equity-Hierarchy Juncture and inter-relational agency. These concepts illustrate how a middle ground theoretical position has utility for generating insights into both local (organisational) and universal level leadership issues. The research shows that a middle ground research position has a high level of utility because, unlike most contemporary research, it can simultaneously contribute to research and practice in a way that does not either separate or collapse these concepts. Rather, a middle ground theoretical position presents a synergy between research and practice that has been neglected in the leadership literature.

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  • Capacity to consent to treatment in forensic mental health care

    Skipworth, Jeremy John (2011)

    Doctoral thesis
    University of Otago

    Mental health legislation is often criticised for being fundamentally inconsistent with a rights-based approach to healthcare. One problem is that it often permits the treatment choices of detained patients with capacity to be overridden. In many jurisdictions this concern has led to legislative reform which gives greater respect for individual autonomy concerning treatment. However, unusual healthcare issues exist for mentally disordered forensic patients who are detained in part to protect third party interests, particularly if the patient is detained following criminal behaviour. Balancing the competing interests in these cases is arguably one of the most difficult ethical and clinical issues in psychiatric practice. To what extent should patient autonomy be respected in the compulsory treatment of forensic patients, and what is at stake if greater respect for a forensic patient’s capacitous treatment wishes is prescribed in law? Very little is known about the epidemiology of capacity to consent to treatment among forensic patients, or even the extent to which it can be reliably and validly assessed in this population. The first main aim of this thesis was to consider how ethical and legal issues relate to mental capacity, with particular reference to their applicability to capacity to consent to treatment in forensic patients. The second aim was to conduct an empirical study to examine the reliability and validity of mental capacity evaluations in forensic patients, followed by an assessment of the demographic and clinical factors which were associated with incapacity in this group. This included an analysis of capacitous treatment-refusing forensic patients. The last aim was to apply this empirical data to the question of legislative reform, and in particular, the consequences were considered of giving greater respect to treatment related decision-making capacity in this population. In a cross-sectional study, 109 forensic patients in diverse clinical settings were interviewed using a comprehensive range of assessment measures. Despite the challenges created by the coercive nature of the treatment setting, the assessment of capacity to consent to treatment was found to be highly reliable, although some concerns regarding validity were identified. A taxonomy of capacity, coercion and consent was developed to assist in the classification of patients. Overall, the majority of participants (66%) had decision-making capacity regarding their treatment. Severity of psychopathology, in particular insight, was highly correlated with capacity, whereas demographic variables were, in general, unrelated to capacity. A small minority of participants (2.8%) were classified as competent treatment refusers . The real impact of permitting capacitous treatment refusal was difficult to determine, but there would appear to be a small number of patients who would challenge the ability of forensic services to provide safe and effective care if their wishes were enacted. Notwithstanding these concerns, it is concluded that there are a variety of ways in which legislators could further promote the autonomy of capacitous and incapacitous forensic patients without significantly compromising the safety of institutional staff, other patients, or the community.

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  • Inducing Anti-Tumor Immune Responses with Antigen Conjugated Virus-Like Particles

    Win, Stephanie Joy (2011)

    Doctoral thesis
    University of Otago

    Virus-like particles (VLP) have been shown to be useful nanoscale platforms in a diverse range of applications including their use as vaccines. They can act as vehicles for the delivery of heterologous antigens to the immune system thereby initiating strong anti-tumor responses. Model tumor antigens chemically coupled to rabbit hemorrhagic disease virus VLP (RHDV VLP) have been shown to delay or prevent the development of tumors in vivo using an aggressive model of murine melanoma. RHDV VLP are amenable to conjugation with a range of peptide antigens, single proteins or complex tumor lysates, all of which are relevant for studying immune responses to tumors in mouse models or with human systems in vitro. Dendritic cells (DC) play a key role in the development of anti-tumor T cell responses due to their ability to take up antigens, process them into peptides and present them to CD8+ T cells on MHC-I by cross-presentation. Inhibitor studies showed RHDV VLP are rapidly taken up by both mouse- and human-derived DC by macropinocytosis and phagocytosis and are subsequently prepared for presentation on MHC-I that has recycled from the cell surface within acidified lysosomal compartments. Additionally, the ability of murine DC to cross-present VLP does not seem to be confined to specific subsets as DC expressing CD8α were able to cross-present VLP-SIINFEKL in vivo, to equivalent levels as other populations of DC. RHDV VLP conjugated to tumor peptides or lysates do not stimulate phenotypic maturation of the DC required for the cross-priming of naïve T cell responses. The addition of an adjuvant, either OK432 or oncolytic reovirus, to DC pulsed with VLP-MART1 or VLP-Lysates, resulted in phenotypic maturation of DC and enabled the priming of naïve T cells able to produce IFN-γ and directly lyse specific target cells. Furthermore, MART-1 specific MHC-I pentamer staining demonstrated the expansion of CD8+ T cells possessing a TCR specific for MART-1 while the T cells took on a more activated, effector memory phenotype through diminished expression of CD45RA and increased expression of CD45RO and CCR7. Importantly, T cell responses primed using VLP-MART1 or VLP-Lysate with either adjuvant were more pronounced than where MART1 peptide or Lysate was used with that same adjuvant indicating a significant benefit in delivery of antigen on VLP. Collectively, these results indicate that VLP-conjugates, together with adjuvant, have the ability to stimulate cytotoxic T cell responses specifically against tumor cells. Production of a VLP able to induce DC maturation was attempted by conjugation of melanoma lysates infected previously with oncolytic reovirus to the VLP (VLP-ReoLysate). Results indicate that these VLP-ReoLysate are able to induce activation of innate NK and NKT cells as well as DC. Furthermore, DC pulsed with VLP-ReoLysate resulted in priming of naïve T cells with cytotoxic capabilities against melanoma cells in vitro, however minimal differences were seen where ReoLysates were delivered alone or conjugated to VLP. Collectively these results demonstrate that the delivery of antigens coupled to VLP, along with an adjuvant, to DC are able to induce strong and highly specific cytotoxic T cell responses against tumor cells to a greater degree than antigens delivered alone. The potential to further modify the VLP to incorporate an adjuvant would further enhance the appeal of VLP as a clinical agent to target tumors.

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  • Lactobacillus dialogues: the impact of cell signalling on gene expression and ecological behaviour of a gut commensal

    Wilson, Charlotte Mary (2011)

    Doctoral thesis
    University of Otago

    Quorum-sensing is a system where genes are regulated in response to changing cell density by the synthesis, release and detection of a signalling molecule to facilitate the coordination of group behaviour such as in the development of a biofilm. Studies in Vibrio, Salmonella and Escherichia identified the autoinducer-2 (AI-2) signalling molecule produced by LuxS, an enzyme widely distributed among bacterial species. The extensive taxonomic distribution of luxS suggested a universal signalling role for AI-2 with potential for interspecies microbial communication. The identification of loss of quorum-sensing phenotypes when luxS is mutated is complicated however by the dual role of LuxS in both the production of AI-2 and catalysis of a reaction in the activated methyl cycle (AMC). Previously a luxS mutant strain of Lactobacillus reuteri 100-23, an autochthonous inhabitant of the mouse gastrointestinal (GI) tract, was developed and found to have altered biofilm formation, lower cellular ATP and a reduced ability to compete with a closely related species in the GI tract of mice. It was hypothesised that loss of quorum-sensing ability affected the phenotype of L. reuteri 100-23. Cells of wild type and luxS mutant L. reuteri 100-23 were harvested from log phase and stationary growth phases, when extracellular amounts of AI-2 were highest and near baseline, respectively. Transcriptome analysis, using a microarray representing the genome of strain 100-23, identified altered gene regulation in the metabolic pathways of methionine biosynthesis, cysteine biosynthesis, and pyrimidine biosynthesis when luxS was mutated. Two prophage regions were down-regulated in the mutant relative to the wild type and circularised phage DNA could be detected in the wild type. The regulation of two genes encoding proteins with LPXTG motifs was affected by luxS mutation during growth in laboratory culture. The expression pattern of one of these genes was similarly affected when the mutant formed in vitro biofilms in a bioreactor and during colonisation of the mouse stomach. Stress response genes were induced in all conditions analysed when luxS was mutated. The metabolite profile measured by GC-MS supported the cellular stress response induced by luxS mutation, and an accumulation of amino acids in the mutant relative to the wild type suggested a redirection of metabolic pathways to compensate for loss of LuxS. Further studies investigated important colonisation features of L. reuteri 100-23 by transcriptome comparison of L. reuteri 100-23 harvested from the mouse stomach to L. reuteri 100-23 harvested from broth culture. Genes involved in the acid tolerance response including glutamate decarboxylase and the urease enzyme were substantially up-regulated during gut colonisation. The urease enzyme was functional and a knockout of the main subunit of the enzyme, UreC, resulted in a strain unable to use urea and with a reduced tolerance to acid. This strain was severely compromised during colonisation of the mouse and constituted less than 1% of the total Lactobacillus population in the stomach, jejunum and caecum seven days after co-inoculation with the wild type strain. Under the conditions analysed in this study, the effects of AI-2-mediated quorum-sensing in L. reuteri 100-23 were negligible and may be limited to the induction of prophage. The majority of transcriptome effects were attributable to the metabolic disturbances caused by loss of a complete AMC. A functional urease enzyme was found to be essential for the successful colonisation of the mouse stomach by L. reuteri 100-23 and in the ability of this organism to compete and persist in the mouse GI tract.

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  • A Framework for Tourism Destination Marketing in Network Destination Structures

    Ermen, David Friedrich (2011)

    Doctoral thesis
    University of Otago

    Tourism destinations are an essential part of the tourism system and are the place where most tourism consumption occurs. In order to achieve a competitive advantage in the market place, individual destinations need to market themselves and provide a service that fulfils the guests needs. This is complicated by the fact that destinations are made up of a multitude of heterogeneous actors that provide the complete tourism experience together. The management of the destination system is facilitated through networks, which provide the governance structure or framework for the destination to function. This thesis analyses the structure of these networks at the normative, strategic and operative management levels to determine the effect they have on the destination. The major bodies of theory used in this thesis are the destination marketing and management literature, drawing heavily on the Swiss tourism and management perspectives, and network theory to examine relationships between actors within the destinations. The Swiss school of tourism management uses an integrated systems approach to tourism planning, applying managerial models to tourism firms and regions. These are complemented by the networks literature, which can be used to analyse the interaction between different components or actors within a given system. Network analysis provides a foundation on which the destination system can then be analysed. Qualitative theory building research allowed for more accurate delineation of destination network types for both research and managerial purposes. The empirical research examined three case studies; Wanaka in New Zealand, Åre in Sweden, and St Moritz in Switzerland to determine how the networks affect the destination management. Interviews with relevant actors in each destination were used to collect data. Secondary documents provided further insight into the cases. Each case was analysed individually first and then they were compared across cases. The findings show that different network structures can be found at the three levels of destination management. The thesis presents new insights into destination networks that take into account the relationships between actors within the destination at the normative, strategic and operative management levels. This provides the framework for destination marketing and other destination wide activities. These activities provide the basis for a sustainable competitive position for the destination. This thesis contributes to the destination marketing literature in three ways. First, The thesis integrates the Swiss tourism and management literature with English literature to suggest a new framework for analysing destinations, based on three levels of management. Secondly, it operationalises this model in three international case studies and clearly differentiates between different types of destination networks, providing criteria for their analysis. Thirdly, the results of the research distinguish key success factors for operating in networks at the three different management levels. In addition, the sources of influence for actors in these networks and success factors for operating at each of the three levels provide a resource for tourism managers to improve the marketing and management of their destination.

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  • Milling Behaviour of Drugs

    Zimper, Ulrike (2011)

    Doctoral thesis
    University of Otago

    Milling is a common pharmaceutical unit operation, which provides two possible pathways to enhance the dissolution rate of poorly water soluble drugs: particle size reduction and solid state form transformation. This thesis is investigating the effect of milling on the solid-state properties and dissolution rate of different BCS-class II compounds. Milling was conducted on an oscillatory ball mill and a media (bead) mill. For particle size reduction, any process induced transformation (PIT), i.e., solid-state alteration during milling needs to be avoided in order to ensure the final product quality. However, the milling conditions applied in industrial settings do not necessarily lead to distinct singular solid-state forms (like defined crystalline polymorphs or completely amorphous forms) of an active pharmaceutical ingredient. Hence, the challenge of this thesis lay in the determination of various degrees of process-induced disorder, which was hypothesized to be generated during milling. X-ray powder diffraction, differential scanning calorimetry and Raman spectroscopy were the analytical methods that were compared with respect to the detection and quantification of solid-state modifications and process induced disorder. Complementarity as well as advantages and disadvantages of each method are investigated and discussed in this thesis. Process induced disorder and particle size are the two opposing responses in a milling operation. A central composite face centered design was utilized to optimize a dry ball milling operation with regard to these responses. The dissolution rate of the optimized formulation was investigated with regard to the impact of process induced disorder and particle size on dissolution. It was found that process induced disorder was negligible with respect to the dissolution rate and the primary particle size could not be translated into a dissolution rate advantage due to particle agglomeration. Since particle agglomeration of small primary particles to larger secondary particles was found to be a hindrance in dry milling processes, wet milling as an alternative milling operation was explored with regard to its effect on process induced disorder and dissolution rate enhancement for the BCS-class II model compound BIX. A PLS model was developed which allowed for the semi-quantitative determination of process-induced disorder in a media milling process. Furthermore, a nano-crystalline drug formulation of BIX was compared to an amorphous drug formulation with regard to dissolution rate improvement. The amorphous drug formulation failed to enhance the dissolution rate of BIX due to recrystallisation upon dissolution. Overall, if the objective is to enhance the dissolution performance of a poorly water soluble drug whilst limiting the introduction of crystalline disorder during processing, nano-crystal drug formulation by wet media milling proved to be a superior formulation approach over dry ball milling and amorphous formulation for the model drug investigated in this thesis.

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  • Innovation and Resources: A qualitative study of start-up entrepreneurial ventures through the lens of the Resource-Based View

    Paradkar, Amit (2011)

    Doctoral thesis
    University of Otago

    Understanding how young entrepreneurial firms achieve and maintain competitive advantage is of critical importance for entrepreneurs and venture capitalists alike. Although innovation is a well-known source of competitive advantage for firms in general and for entrepreneurial start-up firms in particular, the resource-based view holds that the strategic resources (e.g., assets and capabilities) owned by a firm are determinants of a firm’s competitive advantage and thus its performance. Entrepreneurship involves creating and combining resources in profitable combinations, yet the role of the resource-based view (RBV) in explaining these actions largely remains unexplored. This research examines the relationship between innovation and resources in entrepreneurial start-up firms through the lens of the RBV. Specifically, this research aims to: (i) integrate the literature on innovation and the RBV to investigate their influence on the commercialisation of innovation in entrepreneurial firms; (ii) to identify which resources are most strategic for entrepreneurial firms; and (iii) to study how entrepreneurial firms create and combine resources to generate competitive advantage. Based on the prescriptions of extant innovation literature and the RBV, the study proposed that successful commercialisation of innovation and the performance of entrepreneurial ventures requires key resources, and that intangible resources in particular are highly strategic to entrepreneurial firms. These propositions were tested through case studies of 12 New Zealand-based entrepreneurial ventures in a wide range of fields, from technology-based to cosmetics firms. Results indicate that superior business execution capability, along with other intangible assets such as brands, patents and alliances, are crucial sources of competitive advantage for entrepreneurial start-up firms. Entrepreneurial firms should therefore focus considerable attention on the development and retention of such intangible assets and capabilities.

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