250 results for 2010, Undergraduate

  • Rib Fractures in Infants: Retrospective Survey of Fractures and Biomechanical Study.

    Blackburne, William Bligh (2015)

    Undergraduate thesis
    University of Otago

    Literature suggests that rib fractures are highly associated with abuse and the present understanding is that antero-posterior compression associated with the ‘shaken baby syndrome’ is their cause. However, this mechanism rests on a number of assumptions with little experimental data to support them. Recent work using a porcine model of fractures suggests that, in the case of lateral fractures this may be highly unlikely. This work shows a feasible alternate mechanism, that of blunt force trauma (BFT), for the cause of these lateral fractures. A piglet model is used and shows the ease with which ribs fracture as a result of BFT, compared to the difficulty of fracture seen previously in compressive injury. The initial development of a computational simulation of these ribs for use in injury scenarios is also outlined here. Secondly, skeletal surveys from New Zealand’s largest children’s care facility, Starship Hospital, were examined to give a picture of non-accidental injury (NAI) and how its patterns compare with accidental injury in New Zealand. It has been found that, as in foreign studies, there are a number of lesions highly associated with abuse and these include rib fractures, which are highly specific (97%) for NAI. Unusuallyhigh frequencies of lateral-type rib fractures (46.4%) were found and half the cases were found to be unilateral. This is not wholly in line with the currently accepted idea that rib fracture is due to antero-posterior compression, in which bilateral, posterior fractures are said to be most common. Overall, this work brings into question the traditional mechanism of rib fractures, provides a highly useful snapshot of abusive injury in NZ and also sets a strong foundation for future work.

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  • The role of cytoskeletal elements in the trafficking of KCa3.1 to the basolateral membrane of polarised epithelial cells

    Farquhar, Rachel (2015)

    Undergraduate thesis
    University of Otago

    The intermediate conductance, Ca2+-activated K+ channel (KCa3.1) is targeted to the basolateral membrane in polarized epithelia where it plays an essential role in promoting trans-epithelial ion transport. KCa3.1 is found in many tissues in the body and plays an important role in many physiological and pathological processes (e.g., regulation of salt and fluid transport in the gastrointestinal tract, atherosclerosis, sickle cell disease and asthma). Functional KCa3.1 must be targeted to the basolateral membrane, a process that is dependent upon proper cytoskeletal function. The cytoskeleton is comprised of actin and microtubule filaments. Actin filaments are comprised of polymerised G-actin monomers bound to form filamentous F-actin strands. Microtubules are long filamentous structures comprised of tubulin subunits, made from α-tubulin and β-tubulin monomers. This study examines the role of microfilaments and microtubules in the trafficking of KCa3.1 to the basolateral membrane of polarised epithelial cells. To address this, Fischer Rat Thyroid cells grown on filter inserts to form a confluent epithelium were stably transfected with the Biotin Ligase Acceptor Peptide (BLAP)-KCa3.1 construct. This construct allowed for the selective labeling of basolaterally expressed KCa3.1 using streptavidin. Selective labeling of membrane bound KCa3.1 allowed for the measurement of changes in KCa3.1 expression, in response to drugs that disrupt cytoskeletal elements, to reflect changes in KCa3.1 located on the basolateral membrane. This measure allowed for a direct correlation to be drawn between targeted disruption of specific cytoskeletal elements, e.g. microtubules and microfilaments, and expression of basolaterally-located KCa3.1. PCR was used to determine the mRNA expression levels of KCa3.1 in stably transfected cell lines and SDS-PAGE techniques were employed to investigate protein expression levels of KCa3.1. Western blotting was used to explore the effects of Cytochalasin D (Cyto D), Latrunculin A (Lat A), and Myosin Light Chain Inhibitor-7 (ML-7) which inhibit the function of actin (Cyto D, Lat A) and myosin light chain kinase (ML-7) respectively. Toxicity tests were performed to determine cell survival under a range concentrations of 0-20 μM (0, 3, 5 hr) for all three drugs with cell survival reduced with 20 μM at t = 5 hr for Cyto D and Lat A. Cyto D was administered over intervals of 0, 3 and 5 hr at 10 μM resulting in a decreased relative expression of KCa3.1 (compared to control) of 0.6±0.14 at t = 3 and further decrease in the expression of the channel at t = 5 hr with a relative expression of 0.12±0.035 (n = 5, p < 0.05). Lat A was also administered over intervals of 0, 3 and 5 hr at 10 μM causing a relative reduction in the expression of KCa3.1 at the basolateral membrane compared to the control. At t = 3 hr the expression of KCa3.1 was reduced to 0.7±0.065 and decreased to 0.3±0.049 at t = 5 hr (n = 4, p < 0.001). Finally, cells treated with microtubule inhibitor ML-7 showed a relative reduction in KCa3.1 expression of 0.55±0.12 at t = 3 hr, the expression was further decreased to 0.33±0.11 at t = 5 hr compared to the control. These data confirm that microtubules and microfilaments of the cytoskeleton are crucial in trafficking KCa3.1 to the basolateral membrane of polarised epithelial cells.

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  • 11 week Beta-Hydroxy beta-Methylbutyric acid (HMB) supplementation: Effects on body composition and exercise performance in trained athletes.

    McIntosh, Nicholas Dean (2015)

    Undergraduate thesis
    University of Otago

    Background: Originally used in the farming industry to ‘bulk up’ cattle, interest in the leucine metabolite, beta-hydroxy beta-methylbutyrate (HMB), has been growing following a clinical trial which demonstrated significant improvements in strength and body composition in humans. Subsequent trials reaffirmed that previously untrained individuals benefitted from supplementation. However, trials involving athletes have demonstrated mixed results with short (0.05), nor was there a statistically significant difference with respect to skin fold measurements (p>0.05). Conclusion: The increase in body mass found in this study is consistent with other long term (>6 week) HMB supplementation studies. These gains in body mass may have influenced running performance as a larger mass is required to be moved. As no significant differences in body composition or strength were seen, the findings of this study suggest caution needs to be taken when supplementing with HMB as negative performance effects may occur. Therefore close attention to the type of activities required by the athlete needs to be considered prior to supplementation.

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  • Child Mortality after Discharge from a Health Facility Following Suspected Pneumonia, Meningitis and Septicaemia in Rural Gambia

    Chhibber, Aakash Varun (2015)

    Undergraduate thesis
    University of Otago

    Background Two years away from 2015, the decline in child mortality is not fast enough to reach Millennium Development Goal 4. The Integrated Management of Childhood Illness (IMCI) is a strategy that simplifies management of child health. Beyond effective disease management, IMCI recommendations for care following illnesses are based on limited evidence from the field. The aim of this project was to find (1) the magnitude of and (2) risk factors for child mortality following discharge from a health facility in a low-income setting. Methods This study used an established population-based surveillance system for suspected invasive pneumococcal disease in Upper River Region, The Gambia, West Africa. Children that survived admission for suspected pneumonia, meningitis or septicaemia at the Region’s only referral centre (Basse Major Health Centre, Upper River Region) were followed for 180 days after discharge. Vitality status monitored by the DSS informed time-to-death information in a survival analysis that identified predictors of post-discharge mortality. Two multivariable Cox proportional hazards models were constructed. Model A described the clinical syndrome on admission (provisional diagnosis) and risk of post-discharge mortality. Model B used a reverse step-wise approach to find pre-discharge risk factors for mortality following discharge. Results The cohort that survived admission had higher mortality rates than the background rate in the community. Overall, 105 (2.8%) of 3735 patients died during the 6 months of follow-up. Half of the deaths occurred within 45 days of discharge. Approximately half as many patients died in the six months following discharge as died during hospital admission. Age stratified post-discharge mortality rates were three to six times higher than community mortality rates. In addition to demonstrating the protective effect of increasing age at discharge (HR 0.98 [95%CI: 0.96, 0.99] for every month increase in age), Model A showed that, compared to pneumonia alone, a provisional diagnosis of: pneumonia with visible signs of severe malnutrition had a HR 8.74 (95%CI: 4.93, 15.49); meningitis with visible signs of severe malnutrition had a HR of 13.90 (95%CI: 5.43, 35.58); sepsis with visible signs of severe malnutrition had a HR 18.79 (95%CI: 11.65, 30.32). Model B showed independent risk factors associated with post-discharge mortality were: the presence of neck stiffness on assessment (HR 17.60 [95%CI: 7.36, 42.10]); low mid-upper arm circumference (MUAC) (<10.5cm, HR 11.52 [4.59, 28.90]); visible signs of severe malnutrition (HR 3.94 [95%CI: 2.11, 7.36]); non- medical discharge (HR 6.22 [95%CI: 2.98, 13.01]); discharge during dry season (HR 2.33 [95%CI: 1.44, 3.77]); decreasing peripheral arterial haemoglobin oxygen saturation (HR 0.95 [95%CI: 0.93, 0.98] per percent increase); decreasing haemoglobin concentration (HR 0.82 [95%CI: 0.74, 0.90]) per unit g/dL increase); and decreasing axillary temperature (HR 0.70 [0.58, 0.84] per unit oC increase). Conclusion Gambian children in Upper River Region with suspected invasive pneumococcal disease are at increased risk of death following discharge from a health facility, and most of these deaths occur early. There are identifiable risk factors for death, including neck stiffness, low MUAC, visible signs of severe malnutrition, non-medical discharge, discharge during dry season, decreasing peripheral arterial haemoglobin oxygen saturation, decreasing haemoglobin concentration and decreasing axillary temperature. These data add to the evidence base needed to inform the development key guidelines and may be helpful towards development of a tool with clinical utility to identify children for intervention after discharge from hospital.

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

    Wellington, Grace Charlotte (2016)

    Undergraduate thesis
    University of Otago

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

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  • What’s the harm in waiting? Patient harms in the referral waiting gap

    Patel, Vimal (2016)

    Undergraduate thesis
    University of Otago

    Background Patient safety research seeks to improve the delivery of care, and ensure that patients’ risk of injury from healthcare itself is minimised. Referral between primary healthcare, specialist diagnostic agencies (such as community medical laboratories and radiological centres), and hospital based healthcare is common and important in primary care, yet patients have highly variable waiting times before receiving their care. However, there is almost no research exploring what happens to patients while they wait. Aims This study aims to investigate patient’s waiting periods between referral from their General Practitioner (GP) and receiving specialist healthcare. Specifically, this study aims to determine if patients come to any harm in this waiting gap, and if so, which patients are harmed and what types of harm happen. Methods I reviewed 5 years (2003-2007) of healthcare records of 201 general practice patient’s notes. Each consultation record was examined to identify the types of referral that were made and to find evidence of harms while the patient was waiting for referred healthcare. A subset of 101 of these patients also had the records reviewed for investigation types and evidence of harm while waiting for investigation. A broad definition of harm was used to capture a greater number of harms. Harms were categorised as related to referral for investigation, referral to medical specialty or referral to other non-medical specialty. Harms were also graded in severity (mild, moderate and severe) and were described under the following: ‘continued symptoms’, ‘delay in subsequent management’, ‘deterioration of condition’, ‘financial cost to patient’, ‘anxiety/mental harm’ or ‘other’. Comparisons were made between patients whose referrals had evidence of harm in the waiting gap with patients who did not. Comparisons included length of waiting gap, age, gender and specialty referred to and used t-tests or non-parametric tests, as appropriate. Results 5003 Consultation records were reviewed. A referral rate of 0.21 per person per year for medical and non-medical specialties was found, and a referral rate of 1.00 per person per year for investigations was found. 45 of 183 (25.5%) of referrals to medical or non-medical specialties had evidence of harm in the waiting gap, whereas 9 of 105 (1.8%) of referrals for investigation had harm in the waiting gap. Of the 58 total harms, 43 (74.1%) of harms were minor, 12 (20.5%) were moderate and 3 (5.2%) were severe. The largest broad classification of harm was “continued symptoms” with 38 harms (65.5%), followed by “delay in subsequent management” with 14 harms (24.1%) and “deterioration in condition” with 14 harms (24.1%). There were no statistically significant relationships between the age of patient nor sex of patient nor length of waiting time and the incidence of harm in the waiting gap. Conclusion This is the first study of harm in the referral waiting gap. The findings indicate that harm does happen while patients wait for referred care, and more research is needed to explore these harms. While the relatively small number of patients in this study limits the ability to draw robust implications for changed clinical practice, it is a strong starting point for larger, future research.

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  • Umbilical Cord Serum Chemokines and the Development of Atopic Dermatitis

    Townsley, Hermaleigh (2016)

    Undergraduate thesis
    University of Otago

    Background: Atopic dermatitis (AD) is a chronic skin condition characterised by the development of pruritic and inflamed lesions. One key component of AD pathogenesis is a cutaneous hyper-reactivity to allergens influenced by a Th2-polarised immune response. Macrophage-derived chemokine (MDC) and Thymus and activation-regulated chemokine (TARC) are two chemokines involved in this pathological immune response. Research has shown a strong association between MDC and TARC levels in blood and AD severity. Recently, some cohort studies have suggested that levels of MDC and TARC in umbilical cord blood (UCB) may be predictive of whether infants will develop AD during childhood. This cohort study aimed to further investigate the potential predictive value of UCB MDC and TARC for AD development in childhood. Methods: This project involved a retrospective analysis of data obtained from the NZA2CS population birth cohort study. Information about AD-related outcomes was gathered using questionnaires at various time points, along with physical examination of flexural dermatitis and measurement of total and specific IgE levels at age six. UCB MDC levels were measured using enzyme-linked immunosorbent assay (ELISA) techniques for a total of 647 participants. Haemolysis of UCB samples was found to affect TARC measurement; therefore fewer (n = 270) samples were analysed for TARC. Haemolysis of UCB samples did not affect measurement of MDC concentration. Logistic regression was used to calculate odds ratios to determine the association between UCB chemokine levels and development of AD- related outcomes in childhood. Results: UCB MDC and TARC levels were not predictive of development of AD at age six. Neither were they consistently significantly associated with the development of AD-related outcomes such as an itchy rash or atopy. Some statistically significant associations were found, although their value is difficult to interpret as these were isolated findings. UCB MDC levels were significantly associated with the development of an itchy rash at four years of age (p = 0.027) and with the level of specific IgE to cat allergen at age six (p = 0.05). When the data was segregated by sex, UCB MDC levels in males were consistently significantly associated with development of an itchy rash during childhood (p < 0.05). Conclusion: UCB MDC and TARC concentrations are unlikely to be clinically useful biomarkers for the development of AD in childhood. This was the largest cohort study so far to investigate cord MDC and TARC levels as predictors of future AD onset, and the findings are concordant one other large cohort study. Therefore, these results do not warrant further research into UCB MDC and TARC as predictive biomarkers of AD development.

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  • An analysis of vessel loading of export logs at four New Zealand ports.

    Duval, Alfred W. (2016)

    Undergraduate thesis
    University of Canterbury Library

    Over half of New Zealand’s annual harvest was exported as logs in 2015 (MPI, 2016). The large scale and economic importance of log exports highlights the importance of efficient port operations. Productive cycle elements for the log loading operation were defined. The vessel loading cycle was split into six elements: three ‘action elements’ (loading, tallying, and slinging), and three ‘carting elements’ between the ‘action elements’. Time study measurements were carried out at four New Zealand ports (Tauranga, Marsden Point, Gisborne, and Port Chalmers) to identify differences in productive time to load log export vessels. Port Chalmers wasn’t compared to the other ports as it was too different operationally. Loading had the longest productive element time, followed by slinging and tallying, and lastly the ‘carting elements’. Loading was uninfluenced by port but affected by log grade, length, operator skill, and the time of day. Tallying was significantly different between the three ports with Marsden Point fastest and Tauranga slowest. Slinging was quickest in Gisborne and faster whilst loading below-deck and during the daytime. Carting elements were heavily influenced by distance to or from log stack for all four ports. Tauranga displayed the fastest historic gross load rate (JASm³/hour) yet the slowest productive cycle time. Gross load rate is influenced by delays, volume per cycle, and productive cycle time. The difference in productive time and gross load rate could therefore be assumed to be from increased volume per cycle and/or reduced delays in Tauranga. Exporters are fined for loading slower than scheduled. This cost is greater when shipping rates are high as fines are based on shipping rates. A 5% increase in loading efficiency can save the exporter US$11,000 per vessel at historic maximum shipping rates.

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  • Native forest monitoring : tracking changes in native forest remnants.

    Arnold, T. A. H. (2016)

    Undergraduate thesis
    University of Canterbury Library

    Native forest monitoring is undertaken by forest companies as a requirement for certification of their forests by groups such as the FSC. It is important for companies to be able to track changes that are occurring to native forest remnants that are often spread throughout their operational plantation forest estate. Pan Pac tasked me with completing their 2016 native forest monitoring programme and review the results that have been collected since the programme was implemented in 2002. The objective of this was to both gain a better understanding of how the composition of the remnants in their5 estate is changing and to make recommendations on how the programme could be improved in the future. The majority of the 11 Permanent Sample Plots (PSPs) measured were in good or stable condition, several of which showed strong regeneration of the understory over the past 14 years. Three of the sites have been affected by heavy ungulate browsing (deer and/or goats), which has resulted in the continued suppression of the understory vegetation. While all current canopy layers of the PSP have not changed significantly, current and future disturbance such as ungulate browse could result in a change in composition from the current forest makeup. Ungulate browsing has been identified as the biggest driver of change in the native forest remnants within Pan Pac’s estate. To further examine to magnitude of this, exclosure plots could be established in impacted remnants to assess the effect of removal of browsing pests as a basis for Pan Pac to make decisions about future ungulate control. Continued monitoring of native forests is key to be able to identify as well as understand what is happening with native forest remnants. Tracking composition change is important as it allows the forest manager to target management practices such as ungulate control to combat non-natural changes that are occurring.

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  • Falcon Forestry Carriage Series 2 : a case study of productivity and operation.

    Bolitho, Callum (2015)

    Undergraduate thesis
    University of Canterbury Library

    The multiple drivers of workplace safety and increasing productivity are resulting in increased mechanisation within the forestry industry. The use of motorised grapples in cable harvesting is an applicable mechanisation method to the large proportion of steep terrain harvesting in New Zealand. In this dissertation a time study of the Falcon Forestry Carriage Series 2 has been undertaken in order to access its productivity and operation. Mean values of productivity were found to be 54.9m³/PMH for wood extracted from the ground, 64.6m³/PMH for bunched wood and 75.6m³/PMH for excavator fed wood after adjustment for the cycle distance and accumulation type. Longer cycles were found to decrease productivity by 0.15m³/PMH for each meter of cycle distance. Utilisation in the study was found to be 56% of total time which was similar to previous studies. 15% of total study time was accounted for by operational delays, 7% by personal delays and 23% by mechanical delays. Mechanical problems with the carriage occurred 6 times and accounted for 171 minutes or 13.4% of total delay time. Mechanical delay breakdown was similar to that found by McFadzean (2012) who recorded that 15% of total delay time was attributable to carriage mechanical delays. During a study of Operator effect it was found that the inexperienced Operator 3 and Operator 4 had a productivity of 52.2% (not statistically significantly different) and 18.5% (p value <0.05). The effects of accumulation method and cycle distance upon productivity were found to be similar to the results of previous studies, as was the utilisation of time within the study.

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  • Understanding demand for wood products in New Zealand’s major log markets.

    Drummond, Ryan C.M. (2015)

    Undergraduate thesis
    University of Canterbury Library

    New Zealand’s forestry sector is largely reliant on the presence of a strong export market with 57% of the volume harvested being exported of which 99% goes to Japan, the Republic of Korea, China and India. This identifies the need to analyse demand in these countries to better understand their needs in the future. Consumption of wood products per capita is a commonly used metric for estimating demand and was used in this research. Volumes of imports, exports and production were collected from the Food and Agricultural Organisation of the United Nations (FAO) and data for a range of explanatory variables was collected from a variety of official sources. Historical trends in consumption identified that as countries develop socially and economically their consumption shifts from largely solid wood products such as sawn timber to more processed products such as wood-based panels and paper and paperboard. Consumption was modelled using linear regression techniques to develop models which could be used to forecast consumption in the future. A wide variety of potential explanatory variables were considered and the models presented represent the most effective of these. GDP per capita was found to be the single most effective explanatory variable being highly significant (p<0.01) in all models. Price was also found to be a strong determinant of consumption, understandable as price is a major component of supply and demand dynamics. Measures of construction activity were found to be related to consumption of sawn timber in all studied countries and for wood-based panels in Japan. Forecasts produced for consumption in Japan should be used as only an example of the capability of the models presented herein. More work is required to develop these equations into a form where they can be used to more accurately estimate future consumption.

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  • Comparing performance of seedlot types in the Kaingaroa Forest using ground pilots and aerial LIDAR : comparing the performance of open-pollinated, control pollinated and clonal seedlots in a plantation trial in the Kaingaroa forest utilising airborne LIDAR.

    Henderson, Theo J. A. (2016)

    Undergraduate thesis
    University of Canterbury Library

    Problem: As more improved planting stock such as clones and genetically improved seedlings are introduced to the market it is important to properly understand the benefits of each production type. Various breeding programmes make claims around performance of their seedlots but there is a shortage of literature around the performance of these production types in a plantation setting for most production species. Approach: One seedling, two cuttings, and 7 clonal varieties were compared in a plantation setting on a single site. The stand was measured via five permanent sample plots (PSPs) per seedlot. The seedlots were categorised by material production type and compared using pair-wise analysis to find statistically significant differences. The seedlots were then compared individually to find any intramaterial differences. Available aerial LIDAR was then used to estimate tree height for the total seedlot area and establish whether this was an accurate estimate. Average LIDAR height was then used to estimate tree height for each of the five PSPs to establish whether this would improve the prediction of heights and permit its use for large-scale evaluation of genetic material. Results: Categorising seedlots by material type there was no statistical difference for height performance but there was for DBH and basal area. Clones and open-pollinated seedlots showed superior performance over controlled-pollinated material, but not different from each other. Clones showed reduced height variability over non-clones. DBH and basal area variability was also reduced but the difference was only statistically significant versus open-pollinated seedlots. Comparing seedlots individually there was large variation in performance and variability within material types, with clones showing some superiority and non-clones inconsistent improvements. The LIDAR tree height model for whole seedlot area showed to be a significant predictor average PSP height but poorly predicted CV. Predicting PSP area provided with LIDAR improved correlations over whole stand predictions for both values. Implications: The performance superiority for clones over other production types in this trial is not as pronounced as previously suspected. Clones do, however, provide a more uniform crop. The LIDAR tree height model could be used for further analysis but not for height variability without further improvement. Result validity was, however, reduced by the lack of trial replication and randomisation. This is the key limitation and makes guaranteeing improvements are due to improved genetics (not environment) problematic.

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  • Factors which influence corewood stiffness in radiata pine.

    Jones, Grace (2016)

    Undergraduate thesis
    University of Canterbury Library

    Increasing stocking and competition with weeds significantly increased Hitman estimates of stiffness at the significance level α=0.05. Accuracy of models predicting Hitman from TreeTap measurements can be improved by customizing them for particular silvicultural regimes and diameter at 1.4m (DBH). Controlled factors: genetics, wind sway and fertilizer use, did not significantly influence Hitman estimates of stiffness. Tree height did not significantly influence stiffness estimates, but including DBH in prediction models improved models of stiffness estimates. Stiffness in 10 year old Pinus radiata stems was studied in an experiment with the following factors: genetics, herbicide/fertilizer use, stocking and wind sway. Acoustic velocity was used as an estimate of modulus of elasticity (MOE) and was estimated using 2 different tools: Hitman, a resonance based tool used on 2m log sections, and TreeTap, a time-of-flight based tool used on 1.2m outer-wood sections of standing trees. DBH and tree height were also recorded for each tree. Green density was measured using submersion in order to use the formula: MOE = green density∗ acoustic velocity² Stiffness estimates from TreeTap were strongly correlated with Hitman estimates, but were about 30% higher on average. The relationship between stiffness estimates from these tools changed with weed competition and with stocking. No significant difference in stiffness was found between the northwest and the southeast sides of the stems when using the TreeTap tool, and an average value for each tree was used for subsequent analyses. These findings are similar to those from other studies carried out on different sites, and to a previous destructive sample at the same site. There were a few major outliers, but despite these the final model relating TreeTap and Hitman estimates was significant (P<0.0001). Weed competition and stocking significantly affected the intercept (P=5.71e-05 and P=1.08e 05 respectively) of a model predicting Hitman values from TreeTap estimates of stiffness.

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  • Men’s experience of virtual simulation to aid patient education for radiation treatment to the prostate

    Flockton, Alannah - Jayne (2017)

    Undergraduate thesis
    University of Otago

    Prostate cancer affects more than 3000 New Zealand men each year. Many of these men receive a complex type of radiation treatment which requires patients to have a full bladder and empty rectum to aid in the accuracy of treatment delivery and minimise side effects. These concepts can be difficult to explain and current patient education involves verbal and written materials. A 3D immersive teaching tool Virtual Environment Radiotherapy Training system (VERT) can visually simulate and demonstrate how radiation treatment is delivered to the prostate. There is sufficient evidence to support VERT as a useful teaching tool in the academic environment however; using VERT for one-on-one patient education is a novel approach. This qualitative, pilot study set out to explore men’s experience of VERT when it was incorporated into education sessions for prostate radiation treatment. More specifically, how VERT shaped the men’s understanding of how radiation treatment is delivered; why a full bladder and empty rectum is required; and their initial treatment experience. Data collection involved semi-structured interviews one week after the participants had experienced the VERT education and received their first week of radiation treatment. Interpretative phenomenological analysis (IPA) was used to offer insight into the men’s experience of the VERT education session. The findings strongly suggest VERT education enhances patient understanding of radiation treatment through visual learning. There is a preference to have the VERT education delivered sometime near the first treatment appointment and VERT has the potential to support men through engagement, information sharing and encouraging peer support. There is a role for visual tools such as VERT to be included as part of patient education sessions for radiation treatment to the prostate.

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  • Novel Organic Carbon Monoxide Releasing Molecules as a Potential Treatment for Triple Negative Breast Cancer

    Gunatunga, Kishan (2011)

    Undergraduate thesis
    University of Otago

    Carbon monoxide (CO) plays a role in many physiological and pathophysiological processes as a second messenger. Emerging evidence reveals the potential CO has as a therapeutic agent as it has been implicated in the modulation in a range of intracellular functions including apoptosis and proliferation. In the case of cancer, specifically triple negative breast cancer (TNBC), there is very little information regarding the effects of this molecule. Here we hypothesize that the targeted delivery of CO to a tumour will result in an anti-cancer effect in TNBC. The current study examines a novel class of compounds termed organic CO releasing molecules (CORMs) (CO-1 – CO-8) and previously published metal containing CORMs (CORM-2), as potential treatments for TNBC. Firstly a wide range of synthesised novel organic CORMs were screened for toxicity in MDA-MB-231 cells, a model for TNBC, and the lead compound CO-1 was identified from a range of 8 potential candidates (CO-1 – CO-8). Analysis of cell viability data revealed that CO-1 (1 – 200 μM) resulted in significant reductions in cell viability with an IC75 value of around 5 μM in the MDA-MB-231 TNBC cell line, while the by-product of CO-1, BP-1, demonstrated no residual cytotoxic effects. Time course and gas chromatograph-mass spectrometry (GC-MS) studies revealed that the compound released CO at a slow rate with a half-life in vitro between 9 and 24 hours. The ability of CO-1 and CORM-2 to modulate cell death via the induction of apoptosis was demonstrated using Annexin V conjugated to fluorescein (FITC) and propidium iodide (PI) staining followed by FACS analysis. CO-1 was able to induce apoptosis in MDA-MB-231 cells at both low (10 μM) and high (200 μM) concentrations (6% and 6% respectively) with no apoptotic or necrotic effects being observed when cells were treated with the by-product of CO-1, BP-1. The transition metal containing CORM-2 (200 μM) did not increase apoptotic markers compared to control, however treatment of cells with its “inactive” counterpart iCORM-2 (200 μM) resulted in a significant increase (7%) in apoptosis. In addition high (200 μM) but not low (5 and 10 μM) concentrations of CO-1 and CORM-2 produced a significant increase in the percentage of cells with a damaged mitochondrial membrane (3% and 5% for CO-1 and CORM-2 respectively), indicating that CO may have some concentration specific effects in vitro. High (200 μM) concentrations of both CO-1 and CORM-2 were also shown to induce mitochondrial damage in the MDA-MB-231 cell line and further to the potential anti-cancer effects of the novel compound CO-1, we have shown that low (10 μM) concentrations of the molecule causes a 1.2-fold and 1.4-fold increase in caspase 3 and p53 expression and a 1.2-fold increase in caspase 3 activation. The safety of both organic and transition metal CORMs were also assessed in the renal epithelial MDCK cell line. In MDCK cells treated with CO-1 (10 and 200 μM), COM-2 and iCORM-2 (20 and 100 μM) showed histopathological changes indicative of cell death were observed. These changes were not present in cells treated with the by-product of CO-1, BP-1. Interestingly the changes in histological architecture in MDCK cells treated with iCORM-2 appeared more extensive and severe that in cells treated with the active form of the compound CORM-2. Furthermore treatment of MDCK cells with low (10 μM) concentrations of CO-1, 20 and 200 μM CORM-2 and 200 μM iCORM-2 resulted in G2/M cell cycle arrest in the MDCK cell line. The current study proved CO-1, to be a safe and efficacious pharmacological agent with the ability to induce a cytotoxic and cytostatic effect in the MDA-MB-231 and MDCK cell line with no residual toxic effects resulting from treatment of cell with the by-product of CO-1 (BP-1). Our findings cast doubt over the notion that existing transition metal CORMs in their “inactive” form are not without biological effects. Therefore the current study has shown that novel organic CORMs have a combination of properties that translate into a desirable and potential treatment for TNBC.

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  • Predictors of Referral Delay and Treatment Response to Intravitreal Bevacizumab for Wet Age-Related Macular Degeneration

    Ang, Wee Choen (Sebastian) (2017)

    Undergraduate thesis
    University of Otago

    Background: Recent years have seen anti-vascular endothelial growth factor (VEGF) agents revolutionize the treatment of wet age-related macular degeneration (AMD). To ensure optimal outcomes for this time-sensitive disease, current guidelines recommend that patients should be seen in clinic within two weeks of referral and treated with a loading phase of three injections, followed by a follow-up visit for reassessment. However, meeting these guidelines is challenging due to the increasing global prevalence of wet AMD and the accumulating cohort of patients requiring treatment. In addition, services with inefficient referral pathways and limited treatment capacities have been shown to threaten patient access to prompt treatment and increase adverse patient outcomes. Aims and Methods: This project is a two-year retrospective audit conducted at the Eye Department in Dunedin Public Hospital with the aims to (1) assess the efficiency of the current wet AMD referral pathway against contemporary guidelines and (2) identify any risk factors that are predictive of referral delay and treatment outcome. Relevant patient, referrer, referral and clinical characteristics were retrieved from retrospective analysis of clinical records and OCT scans of 113 patients. The outcome measures were referral delay (i.e. duration from point of referral to first assessment clinic); and treatment response measured by changes in visual acuity, changes in central macular thickness (CMT) and clearance of macular fluid. All potential predictors of these outcome measures were analysed via multivariable binomial logistic regression. Results: Only 49% of patients at Dunedin Public Hospital met referral guidelines, but 85% met treatment guidelines. Overall median time from point of referral to first treatment was 10 days. A loading phase of three bevacizumab injections significantly improved mean visual acuity by 5 ± 24 letters (p=0.03) and reduced mean central macular thickness (CMT) by 55μm (p85 years) were associated with an increased likelihood of CMT reduction (OR 9.157; 95% CI 2.6, 31.747; p<0.001 and OR 4.79; 95% CI 1.11, 20.7; p=0.036 respectively), whereas patients with longer duration of symptoms (1 to 3 months) were significantly associated with a decreased likelihood of CMT reduction compared to patients with symptoms of less than one month (OR 1.65; 95% CI 0.044, 0.616, p value = 0.007). Thicker baseline CMT was also found to be significantly associated with a greater reduction of macular fluid (OR 1.475; 95% CI 0.75, 4.578; p=0.017) after treatment, and so were females compared to males (OR 3.9; 95% CI 1.2, 12.58; p=0.02). Conclusion: This study identified that the current wet AMD referral pathway at Dunedin Public Hospital can and should be more efficient, and quality improvement work is warranted to improve compliance to contemporary guidelines.

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  • Nanopore Sequencing of RNA from Breast Cancer Genes

    de Jong, Lucy Clair (2016)

    Undergraduate thesis
    University of Otago

    Abnormal mRNA splicing can disrupt gene function and influence the course of disease. Analysis of abnormal splicing is an important part of determining whether a particular genetic variant found in the population is pathogenic or not. However, to correctly identify abnormal splicing, we must first understand what is normal. This project assessed the isoforms of the genes BRCA1 and BARD1, which are particularly relevant to the onset of breast cancer. BRCA1 is a tumour suppressor gene implicated in breast cancer onset. BARD1 codes for a protein that interacts with BRCA1 and produces a smaller mRNA transcript. Normal exon skipping events have been identified for both BRCA1 and BARD1, however, current methods are unable to reliably identify full transcripts. This has resulted in knowledge of individual exon skipping events but often does not tell us whether multiple events occur in the same transcript. The MinION nanopore sequencer (Oxford Nanopore Technologies), uses a nanopore to produce long-read, single molecule sequences. This has great potential for identifying multiple long isoforms, which is not practical using current technologies. The aim of this project was to examine the ability of the MinION to identify mRNA splicing patterns of transcripts derived from BRCA1 and BARD1. All mRNA from a normal lymphoblastoid cell line was converted to cDNA and targeted genes of interest were amplified by polymerase chain reaction (PCR). All potential isoforms generated from BRCA1 and BARD1 were then pooled and analysed using the MinION sequencer. After trialling many different analysis methods, the read data was analysed using the BLAST-like Alignment Tool (BLAT) with two outputs, a tabular and a graphical format. The tabular format grouped reads into potential isoforms, while the graphical format allowed visualisation of these isoforms and identified the exon/intron boundaries. Using both these formats 34 BRCA1 isoforms and 39 BARD1 isoforms were identified, 24 and 17 of which were potential novel isoforms respectively. Two of these novel isoforms from the BRCA1 dataset (Δ10-17 and Δ11q21) were further verified using Sanger sequencing. This was a proof of principle research project that demonstrated the potential use of the MinION nanopore sequencer for successful characterisation of multiple mRNA isoforms. This research has successfully identified a number of novel isoforms from the BRCA1 and BARD1 genes using the MinION sequencing device.

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  • The effect of Mepitel Film on skin reaction severity in patients undergoing radiation therapy for head and neck cancer: a feasibility study

    Wooding, Hayley (2017)

    Undergraduate thesis
    University of Otago

    Radiation skin reactions are a common side effect of radiation therapy and can be distressing and painful for patients. Head and neck cancer patients receive a high dose of radiation to the skin and are therefore at high risk of acute skin toxicity. There have been many clinical trials investigating topical agents to reduce or prevent these reactions but the evidence to date is lacking and many centres still base their practice on anecdotal evidence. Recently clinical trials in breast cancer patients have shown that using Mepitel Film® (Mölnlycke Health Care AB, Gothenburg, Sweden) reduced skin reaction severity and stopped the development of moist desquamation when used prophylactically (from the first day of radiation therapy). Mepitel Film and other soft silicone dressings that adhere very closely to the folds of the skin, have been hypothesized to decrease skin reaction severity by stopping friction by clothing and allow the radiation damaged skin to repair itself. The aim of this randomised controlled feasibility study in this thesis was to investigate whether Mepitel Film dressings were superior to Sorbolene cream in reducing or managing radiation-induced skin reactions in patients with head and neck cancer Head and neck cancer patients are prescribed a higher dose than breast cancer patients, have an uneven surface for the Mepitel Film to adhere to and have complex non-homogenous dose distributions, This means that testing the effect of Mepitel Film in this cohort would be challenging. Despite this, it was hypothesised that Mepitel Film was superior to standard Sorbolene cream in decreasing the severity of acute radiation-induced skin reaction in patients receiving radiation therapy for head and neck cancer. In order to test this hypothesis a randomised, controlled, multi-centre, international, open label intra-patient feasibility study was conducted in New Zealand and China. This thesis analyses a subset of 12 patients recruited at the Canterbury Regional Cancer and Haematology Service (CRCHS) at Christchurch Public Hospital. For the first six patients, the study area was chosen as the area of first erythema which was divided into equal halves. Each half was randomised to either Mepitel Film or Sorbolene cream. Mepitel Film was applied as soon as erythema was visible (management protocol). For the next six patients, the study area was chosen at the planning stage to include an area of relatively uniform high dose (>40Gy). This area was divided into two equal halves; one half was randomised to Mepitel Film the other half to Sorbolene cream. Mepitel Film was applied from day one of radiation therapy treatment (prophylactic protocol). Sorbolene cream was applied twice a day by the patient. The Modified Radiation-induced Skin Reaction Assessment Scale (RISRAS) and the Modified Radiation Therapy Oncology Group (RTOG) skin toxicity score were used to assess skin reaction severity three times a week. Patients also filled out the New Zealand validated Distress screening tool once a week and completed exit questionnaires at the end of the follow-up period. Thermoluminescent dosimeters (TLDs) were used to measure the actual dose to the skin underneath Mepitel Film and the control cream for all patients. When results of all 12 patients were combined, there was a statistically significant decrease in skin reaction severity in favour of Mepitel Film of 29% for combined scores, of 15% for researcher scores and of 49% for patients’ scores (p= 0.001, 0.002 and 0.004 respectively). The difference in peak RISRAS score between skin covered with Mepitel Film and control skin covered in cream was also significantly lower (p=0.02). The results were disappointing compared to those reported by the breast cancer trial where skin reaction severity was reduced by more than 90% when Mepitel Film was used prophylactically. Several factors may explain the lack of effectiveness of the Mepitel Film in this patient cohort. Dose to the skin was significantly higher in head and neck cancer patients and Mepitel Film did not adhere well to skin with heavy beard stubble, which meant Mepitel Film needed to be replaced almost daily for the first few weeks of radiation therapy. The latter may also explain why there was no difference in the Mepitel Film effect between the skin of patients on the management protocol and those on the prophylactic protocol which should have had the strongest skin protective effect. In addition, compared with skin covering the breast area, skin in the neck area may be “tougher” and less likely to benefit from “friction protection”. The results suggest that Mepitel Film does reduce skin reaction severity in head and neck cancer patients but the increase in skin folds, beard growth and high skin dose mean that the protective effects of Mepitel Film are limited, particularly in men with heavy beard growth. Mepitel Film appeared to be more effective in women but there were too few women in this trial to perform a statistically meaningful analysis. Future research should include clinical studies in different cohorts of head and neck patients, such as in women and men with less beard growth.

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  • Development of Novel Triadin-Based Biosensor for the Quantification of H2O2 in the Cardiac Dyad Microdomain

    McLachlan, Julia Jocelyn (2016)

    Undergraduate thesis
    University of Otago

    Release of Ca2+ from the sarcoplasmic reticulum (SR), mediated by the activation of the ryanodine receptor (RyR2), initiates myocardial contraction. This process of Ca2+-induced Ca2+ release is confined within a 20 nm region termed the dyad, located between the transverse tubule and the SR. Architectural properties of the dyad restrict diffusion of Ca2+ and other intracellular messengers to create a unique, subcellular microdomain. Previous research has shown that endogenous producers of reactive oxygen species (ROS) are abundant within the dyad, and have attributed alterations in Ca2+ release with the oxidation of RyR2. However, the spatiotemporal dynamics of ROS within this microdomain remain unquantified due to an absence of tools that enable subcompartmental ROS resolution. Therefore, this research aimed to utilise the recent development of genetically encoded redox biosensors, capable of ROS detection, to create a biosensor tethered to the N-terminus of the dyadic protein, triadin. A Human Embryonic Kidney (HEK) 293 cell model was used to characterise two ROS (H2O2) sensors, HyPer3 and roGFP2-Orp1, in vitro to determine the biosensor more suitable for the triadin-based construct. Using single-cell imaging, HEK 293 cells transiently transfected with HyPer3 or roGFP2-Orp1 were superfused with a range of oxidising and reducing agents. Based on these data, roGFP2-Orp1 exhibits a greater dynamic range, increased sensitivity, and faster oxidation-reduction kinetics than HyPer3, and thus was selected for the triadin-based construct. In parallel, single-cell Ca2+ imaging was used to confirm that co-expression of triadin has a neutral effect on RyR2 function. HEK 293 cells expressing RyR2 WT or RyR2 WT + triadin were loaded with the cytosolic Ca2+ indicator, Fluo-4 AM and superfused with 0.1–1 mM Ca2+ to activate RyR2 WT. These data found a non-significant (p = 0.9) difference in Ca2+ release in RyR2 WT (61.9 ± 3.1%) and RyR2 WT + triadin (60.3 ± 3.5%) cells exposed to 1 mM Ca2+. To create roGFP2-Orp1-triadin, overlap extension PCR was used to generate an SfaAI restriction site that enabled roGFP2-Orp1 to be subcloned into the triadin plasmid. However, the development of roGFP2-Orp1-triadin was unsuccessful. This research highlights a novel method for H2O2 quantification within the dyadic microdomain. Characterisation of HyPer3 and roGFP2-Orp1 revealed that roGFP2-Orp1 exhibits the sensitivity and reversibility required for an in vivo biosensor. In addition, co-expression of triadin has a neutral effect on the properties of RyR2-mediated Ca2+ release, which indicates that triadin is an appropriate tether for the dyadic localisation of roGFP2-Orp1. Future directions include the generation of an animal model to further understand the spatiotemporal dynamics of ROS in relation to alterations in Ca2+ release in vivo.

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  • The proportion of fast and slow neuromuscular junctions in young and old mice

    Lloyd, Jordan (2017)

    Undergraduate thesis
    University of Otago

    Human skeletal mass and strength increase from birth until ~35 years of age, thereafter a decline in mass and strength occurs in a process called sarcopenia. Beyond 60 years of age muscular weakness falls to a point where it imposes physical disability and individuals lose the ability to live independently. The loss of muscle mass and strength can be attributed, at least in part, to a fast to slow muscle fibre type transition (increased proportion of slow type muscle fibres. An age associated change in the innervation of skeletal muscle with ageing is a probable underlying cause of this fibre type transition. Muscle fibre types are determined by their innervating axon; fast muscle fibres are innervated by fast axons forming fast neuromuscular junctions (NMJs) and slow muscle fibres are innervated by slow axons forming slow NMJs. If a muscle fibre is innervated by a motor axon of the wrong type e.g. a fast muscle fibre is innervated by a slow axon, that axon converts the muscle fibre type to slow. The present study hypothesised that the reduction in the proportion of fast muscle fibres seen in ageing may be caused by a selective loss of innervation of fast muscle fibres with a subsequent reinnervation by slow axons resulting in the conversion of the fast muscle fibres to slow muscle fibres. This fast to slow muscle fibre type change would therefore be coupled with an increased proportion of slow NMJs with a reduction of fast NMJs (a fast to slow NMJ transition). To determine this, a comparison of the proportion of fast and slow NMJs present in the soleus (containing both fast and slow muscle fibres), and extensor digitorum longus, (containing almost entirely fast muscle fibres) of young (2-2.4 months old) and old (20-24 months old) C57BL/6 mice was made. Immunohistochemistry was used to selectively label slow NMJs by targeting SV2a, a synaptic vesicle protein present only in the nerve terminals of slow axons. Nicotinic acetylcholine receptors (nAChRs) and Synaptophysin, present in all nerve terminals, were used as a general marker for NMJs. The proportion of SV2a positive (slow) NMJs was compared to the proportion of SV2a negative (fast) NMJs in young and old mice to determine whether there was a difference in the proportion of slow and fast NMJs with ageing. Sectioned muscles were viewed by widefield fluorescence microscopy. An average of 180 NMJs were counted in each soleus muscle and 162 in each EDL. A reduction in the proportion of fast nerve terminals with an increase in slow was found in the soleus muscle, 40.41 ± 3.3% of young NMJs were fast and 59.59 ± 3.3% were slow, of old NMJs 10.80 ± 4.1% were fast and 90.20 ± 4.1% were slow. No change was found in the EDL, 89.66 ± 6.3% of young NMJs were fast and 10.44 ± 6.3% were slow. Of old NMJs 90.06 ± 2.5% were fast and 9.94 ± 2.5% were slow. There was an insufficient number of EDL muscles used (n=2) meaning no valid statistical analysis could be drawn from the EDL results. These observations suggest that in the soleus there may be a deinnervation of fast muscle fibres with a reinnervation by slow axons occurring which promotes an increase in the proportion of slow NMJs with ageing and reduces the proportion of fast NMJs. This deinnervation-reinnervation process may underlie the increase in slow muscle fibres with a reduction in fast muscle fibres seen in the ageing soleus.

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