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Prognostic Molecular Markers of Response to Radiotherapy in Rectal Cancer
Get PDFColorectal cancer (CRC) is the second most deadly cancer globally, and 30% of these cancers occur in the rectum. The primary treatment for CRC is surgery, often radiotherapy with adjuvant chemotherapy is used before or following surgical resection.
Treatment carries with it a high cost and side effect burden while response rates remain unpredictable. Approximately 20% of patients have total tumour regression post chemoradiotherapy; however, most patients receive only partial or no benefit from treatment. The ability to predict which patients would benefit from standard treatment and those who should be directed to an alternative treatment or an accelerated pathway to surgery would potentially avoid lengthy and costly treatments that may only cause side effects for patients, improving survival rates and quality of life.
In this study, the microbiome, immune cells and patient gene expression were evaluated for their use as predictive biomarkers for response to chemoradiotherapy in rectal cancer patients. Tumour and adjacent normal tissue biopsies were taken before treatment and had DNA and RNA extracted and sequenced.
First, the methodology for analysing microbiomes via shotgun sequencing data was evaluated and improved, increasing taxonomic assignment accuracy by 11% and potentially decreasing analysis time more than nine-fold. Secondly, the sequencing technologies, Oxford Nanopore, 16S rRNA and RNA-sequencing, were evaluated for their ability to assess the microbiome. The results demonstrated that platforms had concordance with one another; however, this was reduced at the species level.
Third, microbial transcription was used to assess rectal cancer microbiomes, correlating them with response rates. The results showed that microbial diversity did not contribute to radiotherapy response, but that individual microbes may influence response. It was hypothesised that species such as Hungatella hathewayi, Fusobacterium nucleatum, Butyricimonas faecalis, Alistipes finegoldii, Bacteroides thetaiotaomicron, and B. fragilis may contribute to tumour regression by modulating metabolism and immune responses.
Third, the abundance of infiltrating immune cells was predicted using RNA-Sequencing data. Analysis indicated that the abundance of M1 macrophages and resting mast cells were correlated with response, while microbial transcription was correlated with the abundance of allergic and anti-tumour effector cells, as well as antigen-presenting cells. It was hypothesised that the microbiome might modulate anti-tumour immune responses directly, and indirectly by altering the tumour microenvironment. Microbes may help maintain a population of anti-tumour effector and antigen-presenting cells for tumour-antigen presentation during tumour cell death and neo-antigen uptake, which may be otherwise exhausted by targeting aspects of the inflammatory tumour microenvironment (i.e., lipid phagocytosis, anti-bacterial and allergic responses).
Lastly, machine-learning was employed to establish a panel of molecular biomarkers predictive of response, including microbial transcription, immune cells and gene expression. The final model demonstrated the ability to predict response with a 7% overall error rate, and that predicting response relied mostly on normal and tumour tissue gene expression, and tumour infiltrating immune cells.
This study provides a panel of prognostic biomarkers which could be utilised to predict patient response. Additionally, it provides evidence for microbial-immune interactions that could be manipulated to enhance treatment and increase response rates
Understanding Processes of Rural Change in New Zealand: The Case of Maniototo
Get PDFRural places are extremely diverse and represent far more than the agricultural activity often associated with them. They provide lifestyles to people and communities and are celebrated as places of symbolic importance (Cloke, 2006; Woods, 2011). However, the recent development of rural areas have largely been dictated by the trajectory of the agricultural industry. This is exacerbated by external forces and non-agricultural demands. This is due to complex links between national-level policy and the reflection of this on-farm (Cloke & Goodwin, 1992; Wilson, 2007).
Recent rural geography identifies how ‘rurality’ is a social construct, constantly being (re)shaped by forces within rural places (Halfacree, 2006). A range of national and local stakeholders interact across scales to produce the ‘reality’ of life for rural communities. Within rural research, this ‘reality’ has been framed within concepts such as productivism and post- productivism (Ilbery & Bowler, 1998; Walford, 1999; McCarthy, 2005). Literature on the post- productive transition and multifunctionality have been used to explain how rural places have changed over time. However, these are often taken from the perspective of Britain and the European Union. Adding to this literature, this research investigation aims to explore rural and agricultural change in the context of New Zealand.
Rural changes within New Zealand have been inherently linked with the British productivist regime. The drive to become the ‘farm of Britain’ within New Zealand saw investments and interventions into the industry to enhance the intensification and commercialisation of agriculture. Subsequently, the withdrawal of state assistance in the 1980s led to a period of decline. In response, rural areas are now diversifying their on-farm and off-farm economies to improve local economic sustainability and rural social and cultural capital. Within the literature, these changes have been theorised as the ‘post-productive transition’ (Cloke & Goodwin, 1992; Halfacree, 1993; 2006; Woods, 2011). However, most important to this thesis is the application of these ideas in a local context. The chosen case study of Maniototo largely mirrored the development trajectories of other rural New Zealand areas and provided a means to understand local place-specific dynamics.
Using a combination of key informant interviews and historical information, this thesis identifies to identify how rural actions and agendas at a national level (New Zealand) were reflected through a wide-range of local impacts in Maniototo. The findings of this research demonstrate that, while ideas of productivism are applicable in the national and local context, there was insufficient evidence in Maniototo to suggest a shift to post-productivism that the concept of a ‘transition’ implies. As a result, the concept of multifunctionality serves as a better lens to understand the reality of diverse rural change in New Zealand and Maniototo. Further, if research is to continue to frame change within the transition, it must give substantially more focus to the era of ‘pre-productivism’
A Comparative Analysis of Emotion Recognition: Young Versus Older Adults Across Gender and Cultures
Get PDFThe purpose of this research was to investigate emotion recognition in adults across age, gender and culture. Using the six basic emotions of anger, disgust, fear, happiness, sadness, and surprise as stimuli, the aim is to examine whether men and women benefit differently from eye and mouth gazing. Comparisons will be made, first, between male and female participants, second, between young and older adults and third, between Europeans and South-east Asian Chinese. The dependent measure will be correct responses to emotion recognition items. Six basic emotions were shown to 108 young adults (M20 years) and 109 older adults (M70 years) from European and Asian Chinese descent. The two-part experiment which consisted of a web-based survey and the use of an eye-tracker, was conducted in New Zealand (NZ) and Singapore (SG) with facilities provided by the Psychology departments of the University of Otago and the National University of Singapore respectively. I found age-related deficits across cultures and disparity in emotion recognition with NZ Europeans participants outperforming their south-east Asian Chinese counterparts in all emotion recognition tasks. While older women benefitted more from nose gazing, older men’s mouth gazing was associated with worse emotion recognition. In addition, higher depression and loneliness, and lower well-being correlated with worse emotion recognition for younger adults
The behaviour of the banded dotterel, Charadrius bicinctus.
No full textA comprehensive study has not previously been made of any aspects of the Banded Dotterel's ecology or behaviour. […]
Two study areas were used for this research. One was the environs of Lake Wainono (Fig. 1), a small lagoon on the east coast of the South Island - a typical coastal wintering site for Banded Dotterels, which were present there throughout the year. The behaviour of nonbreeding flocks was observed from January to June 1977 there. Observations in this area were made on feeding preferences, techniques and habitats, daily routines, flock sizes and reactions to predators.
The other study area was the Cass River delta (Fig. 2), near Lake Tekapo. This was a typical inland breeding ground and breeding behaviour was studied from June 1977 to January 1978. [Extract from Introduction
Impact of Active Commuting, Organised Sport and Physical Education on Overall Physical Activity in a Sample of New Zealand Female Adolescents
Get PDFBackground: Physical activity (PA), specifically moderate-to-vigorous PA (MVPA), is associated with better health outcomes in adolescents. Active commuting to school, participating in organised sport and physical education (PE) have been shown to increase adolescents’ daily levels of PA, but have never been investigated in a nationwide cohort in New Zealand. Having a better understanding of how these domains of PA influence overall PA can better inform future interventions in adolescents.
Objective: To investigate the patterns of PA in a sample of adolescent females in New Zealand. In particular this thesis will describe how active commuting, participation in organised sport and participation in school PE contribute to the total amount of light PA (LPA) and MVPA accumulated over a 24 h day.
Methods: This sample included 114 female adolescents, aged 15-18 years, from the 2019 SuNDiAL study. Participants completed a Dietary Habits, Motivations, Attitudes and Beliefs questionnaire online, which included questions about each PA domain of interest: mode of active transport, participation in sport and participation in PE. PA was measured using ActiGraph accelerometers worn continuously for seven days.
Results: On average, participants spent 437 min/d (7 h 17 min) sleeping, 711 min/d (11 h 51 min) in sedentary time, 220 min/d (3 h 40 min) in LPA and 42 min/d in MVPA. Twenty four percent of participants met PA guidelines. Sixty eight percent participated in organised sport and accumulated, on average, an additional 46 min/d (95% CI 17.8 to 74.5) of LPA and 17 min/d (95% CI 8.5 to 24.5) of MVPA compared to those who did not. Thirty six percent participated in PE and accumulated, on average, an additional 37 min/d (95% CI 7.7 to 65.9) of LPA and 7 min/d (95% CI -1.7 to 16.4) of MVPA compared to those who did not. Twenty one percent used active transport, and accumulated, on average 11 min/d (95% CI -51.3 to 30.1) less LPA and an additional 12 min/d (95% CI -0.3 to 24.1) of MVPA compared to those who did not. In the hour directly before and after school, compared to those that used motorised transport, those that actively commuted accumulated an additional, 5 min/d (95% CI 1.4 to 8.6) of MVPA before school, and 4 min/d (0.6 to 6.9) respectively. Participants who participated in one, two or three PA domains of interest accumulated an additional 11 min/d, 15 min/d and 35 min/d of MVPA respectively.
Conclusion: Findings from this study confirm that majority of female adolescents are not meeting PA guidelines. Furthermore, active transport and participation in organised sport and/or PE result in meaningful increases in LPA and MVPA, with the greatest difference seen for those that participate in organised sport. For every additional PA domain of interest, time spent in MVPA was increased, suggesting that a combination of PA domains is an important concept to consider when targeting engagement in PA for adolescent females
Intakes and Food Sources of Fat Among Adolescent Males in New Zealand
Get PDFIntroduction: Both inadequate and excessive intakes of fat can lead to negative health consequences. Adolescence may be an important period where longer term food habits are formed. This is also a time of increased autonomy around food choice, which may lead to a higher intake of processed foods high in saturated fat. Few studies have assessed intakes and food sources of fat among adolescents. In addition, only a limited number of studies separate males from females or assess fatty acid composition. Also, the most recent data among New Zealand adolescents are dated and up to date information is needed to inform public health initiatives.
Objectives: The aim of this study was to determine current intakes, composition, and the main food contributors of fat in the diets of adolescent males in New Zealand.
Methods: A sample of 135 adolescent males were recruited from high schools in six centres between February 2020 to April 2020. Participants completed questionnaires on demographics and dietary habits, and two multiple pass 24-hour recalls, height, and weight measurements were taken. The Multiple Source Method was used to adjust for intra-personal variation. Statistical comparisons among demographic groups were made by calculating mean differences and 95% confidence intervals between groups to see if they were statistically significantly different. Results: Mean intakes as a percentage of total energy for total, saturated, monounsaturated, and polyunsaturated fats were 37.5%, 14.0%, 13.9%, and 5.6%, respectively. For total fat, 69.6% of participants had intakes above the recommended range. For saturated fatty acids, 3.9% of participants intakes fell within the recommended intake range, and 96.1% exceeded the recommended intake. Monounsaturated fatty acid intakes could not be compared with a recommended range due to New Zealand not having specific recommendations for this nutrient. For polyunsaturated fatty acids, 67.6% of participants fell short of the recommended intake range, while 2.0% exceeded the recommended intake. Intakes of fats by New Zealand Deprivation Index (NZDep), ethnicity, and Z-BMI (body mass index) weight categories were similar with no statistically significant differences.
Poultry was the top contributor of total fat intake, providing 11.9%. The following top contributors were milk (6.7%), grains/pasta (6.7%), bread-based dishes (6.5%), cheese (5.4%), and potatoes/kumara/taro (4.9%). The top five contributors to saturated fat intake were poultry (10.8%), milk (10.2%), cheese (7.8%), bread- based dishes (6.6%), and grains/pasta (6.3%). The top five contributors to monounsaturated fat intake were poultry (14.3%), grains/pasta (6.4%), potatoes/kumara/taro (6.2%), bread-based dishes (6.1%), and nuts/seeds, (5.7%). The top five contributors to polyunsaturated fat intake were poultry (12.3%), grains/pasta (6.9%), potatoes/kumara/taro (6.7%), bread (6.4%), and bread-based dishes (6.1%).
Conclusions: The current study is the most recent cross-sectional study to assess fat intakes of adolescent boys in New Zealand. Findings illustrate an excess in the intake of total and saturated fats, and low intakes of polyunsaturated fat. These results reflect the supporting literature from New Zealand and overseas. It is essential that public health initiatives focus on intake of fats, in order to combat the array of non-communicable diseases influenced by nutrition
Policy and planning in urban and peri-urban agriculture: The cases of Uyo and Benin City, Southern Nigeria
No full textIn Africa, the practice of urban and peri-urban agriculture (UPA) can be traced back to ancient civilizations. However, in recent times, farming in the developing world more broadly, is promoted for its contribution to household food security and poverty alleviation. Much research effort has thus been geared toward establishing these benefits, especially as urban poverty and unemployment continue to rise. Despite these benefits, UPA is still often considered illegal in many countries, with little official recognition and support from urban authorities. This attitude on the part of officials is said to stem from the restrictions on urban farming during the colonial era through planning policies. The inclusion of UPA in urban plans and the formulation of supporting policies are proposed as a way to ensure its future sustainability and enhance its potential benefits.
The most populous country in Africa, Nigeria, provides important case study cities for several reasons. First, the legal and planning context of UPA has not previously been studied in depth. Secondly, it allows for the comparison of the historical significance of UPA between a precolonial metropolis, Benin City, and the city of Uyo, which developed in the context of colonial planning regulations. Thirdly, there are gaps in our understanding of UPA in Nigeria, especially in relation to class and power. Using key informant interviews, questionnaire surveys and observation, this study has investigated the nature, significance, planning and policy implications of UPA in the two cities.
This thesis explores the significance and planning context of UPA in Nigeria through a historical lens. It examines the policy implications of these findings, as well as the potential opportunities and limitations for the support of farming and its inclusion in urban plans. It argues that UPA is not simply a technical fix to the existing system, but a potential driver for positive political, environmental, social, and economic transformation and, given its significance, there is a need for alternative conceptual framings of the practice in Africa beyond survival and poverty alleviation. It is cautioned that UPA is not in itself a way out of poverty, but an important component of robust food security and poverty alleviation strategies, therefore, necessitating its inclusion in urban food policies and development strategies. While this study problematizes support and policy in the context of rapid urbanisation and the resulting pressure on land, support and policy are, nonetheless necessary. However, such policy must be sensitive to participating households on the margin and any support must be aware of the political outcomes, whether intentional or not
How to Compute Compensation for the Extinguishment of Native Title in Australia: Northern Territory v Mr A. Griffiths (deceased) and Lorraine Jones on behalf of the Ngaliwurru and Nungali Peoples
No full textThis note explains Northern Territory v Griffiths (‘Timber Creek’), which is a native title case concerning land valuation in the northwestern corner of Australia’s Northern Territory. It is an important case because it is the first to articulate how to compensate Aboriginal and Torres Strait Islander peoples for the extinguishment of native title rights under the Native Title Act 1993.Peer Reviewe
New Zealand Deprivation Index 2018 - TA57: Westland District
No full textFor further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/
NZDep2018 analysis of census 2018 variables - Overall (New Zealand)
No full textFor further information about data sources, interpretation of the graphs, and cautions, please see the separate Introduction Chapter.
All data relating to the 2018 census is provided by Stats NZ, https://www.stats.govt.nz/