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Effect of sitting postures on the hemodynamics of the popliteal and femoral veins
No full textIf one were to choose a single object to epitomise the discipline of Design, it could easily be the chair. Most buildings, vehicles or machines contain them. Many of us find ourselves compelled to sit in seats or chairs for eight hours, or more, every day. However, the health implications of this extended chair use are not well understood. Particularly, there is little quantitative research on how the act of sitting affects venous blood flow in the legs.
In 2001, the Joint Aviation Authorities of the European Union asked for research that would test how venous physiology responded to different seat designs. They wondered if current aircraft seat design could adversely affect blood flow in the legs, possibly causing the increased risk of venous thrombo-embolic diseases (VTE) found in air travellers.
A 2007 study found a significant correlation between travelling by air with a 320% increased risk of developing VTE disease. Moreover, this study also showed that shorter travellers, when compared to averaged sized travellers, had a further 263% increased risk of developing VTE.
For this present study, fifteen healthy adult subjects with uncomplicated popliteal/femoral veins were recruited. They sat at three different seat depths and with three degrees of foot support: (1) unsupported (dependent), (2) extended and (3) supported. Doppler ultrasound was used to record cross-sectional diameters of the popliteal/ femoral vein at seven points distributed from the popliteal fossa, behind the knee, to a point 2 cm distal to the sapheno/femoral junction, in the upper thigh. The peak systolic velocities (PSVs) and time averaged mean velocities (TAM) of the venous blood were recorded and the volume flow rate of blood, calculated.
The femoral vein must pass through he adductor hiatus, a small rectangular opening in the adductor magnus tendons. The adductor hiatus was discovered to be the site of dramatic decreases in lumen diameter and corresponding large increases in PSV in every subject as they sat with their legs unsupported. The constriction extended at least 5 cm distal and proximal to the adductor hiatus. There was a 68% mean decrease in venous volume flow rate at one measurement point, distal to the adductor hiatus.
One subject was excluded from the main study because she had incompetent valves in her calf muscle. When she sat with unsupported legs, blood flow ceased in a 12 cm section of her popliteal/ femoral vein. This was unexpected and concerning.
When the legs of the 15 subjects were unsupported, an acute narrowmg formed in thefemoral/popliteal vein. Conversely, when their legs were correctly supported, normal hemodynamics were restored. This may help explain the increased risk of VTE experienced by airline passengers. The current design of economy class seats may preclude many passengers from sitting with fully supported legs. Therefore, it is recommended that seating designers, engineers, manufacturers, researchers and consumers become conscious of the effects that seat designs and seating postures have on the return of the blood to the heart. The resultant seat designs should allow unimpeded venous blood flow in the legs of people, regardless of their height
There is No Water Coming Out of the Tap. An Interdisciplinary Approach to Understanding Water Resources in the Jhikhu Khola Catchment, Nepal
No full textWater resources in Nepal are vulnerable to over consumption and degradation. Agricultural intensification has led to high applications of fertiliser and pesticides, that degrades local water quality through elevated concentrations of nutrients, while population pressures have increased water demand leading to river-bed drying and exacerbated sanitation and hygiene issues. These issues are explored through a case study analysis of the Jhikhu Khola catchment in the Middle Hills region of Nepal, which exemplifies the intersection of intensified agriculture, population, and migration. To meet increasing demands, groundwater wells in the region have been developed haphazardly. The conjunctive (surface water groundwater or rural urban) and unregulated use observed in the Jhikhu Khola highlights the lack of effective water management. Water resources are often approached from a narrow perspective that limits the connection between technical data and the everyday issues that water users face. The societal hydrological nexus within the Jhikhu Khola catchment illustrates the disparities between rural and urban areas and the contamination issues they face. In this setting there are clear asymmetries between the degradation of upstream and downstream water resources. To conceptually frame these management deficiencies, a common pool resource lens was utilised, as water is central to many people lives but there is a continued lack of formal water rules. To effectively integrate the complex issues that water users face, a mixed methodology was employed. Water quality was quantified by measuring the heavy metals, suspended sediments, nitrogen concentrations, as well as pathogenic indicators: E. coli and total coliforms. Additionally, semi-structured interviews and key informant interviews were conducted with water users and experts, respectively. The key findings of the study indicate that every site was contaminated with total coliforms and E. coli. Lower riparian and Hill region water users face acute water scarcity because of upstream appropriation and a lack of groundwater infrastructure. The development of groundwater sources has reduced the value of surface water, leading to degradation. Finally, the significant variations in the use of water and the lack of social capital between water users presents a considerable barrier to cooperative water management. For sustainable and equitable access to water resources, there needs to be effective water management practices developed to prevent further water degradation in the Middle Hills region as water use changes in response to population pressures and changing land use
An Epigenetic Analysis of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
No full textMyalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease affecting approximately 20,000 New Zealanders. Patients experience lifelong persistence of the disease with symptoms including a characteristic post exertional malaise, and dysfunctions in cognition, sleep and the autonomic nervous system. Symptoms are severe enough to prevent normal function, leaving a significant proportion of patients house or bed bound greatly reducing quality of life. Prior research and disease presentation indicates a multi-systemic pathophysiology primarily involving metabolic, immune and neurological dysfunctions. Susceptibility is believed to be a combination of a genetic predisposition in combination with environmental stressors. Recent investigative efforts have turned to epigenetics in order to further understand the disease. DNA methylation is a well-characterized epigenetic modification that is linked to changes in gene expression, especially when it is found within the regulatory regions of the genome such as promoters. Additionally, DNA methylation is a malleable, environmentally affected regulatory modification with the potential to provide insights into systematic changes linked to the disease. This investigation aimed to characterize, in depth, the DNA methylation patterns of ME/CFS patients compared with age and gender matched healthy controls.
In order to determine the DNA methylation variation in ME/CFS a cohort of 10 patients and 10 matched controls were investigated in the study. DNA was extracted from peripheral blood mononuclear cell fractions purified from whole blood. Following quality assessment of isolated DNA, DNA fragment libraries were prepared for Reduced Representation Bisulfite Sequencing (RRBS). The RRBS libraries were sequenced using high throughput next generation sequencing. The subsequent data were analysed using multiple bioinformatic platforms in order to determine patterns of differential methylation between the patient and control groups. RRBS designed MethylKit and DMAP analysis pipelines were utilised in order to investigate changes at each individual cytosine and at clustered cytosines within DNA 40-220bp fragments respectively. Additional methylation variation was investigated across genomic features of interest including promoters, enhancers and gene bodies. Genes identified associated with gene body differential methylation were then utilised for further pathway enrichment analyses.
With appropriate statistical significance thresholds, Methylkit identified 394 differentially methylated cytosines and DMAP identified 76 differentially methylated fragments. Manual inspection of the data identified four clusters of MethylKit cytosines overlapping or in close proximity to DMAP fragments. These clusters identified regions of regulatory importance for 16 protein-coding genes. Further independent regulatory feature analysis identified 22 promoter regions associated with 45 differentially methylated cytosines (utilising MethylKit data) and 11 promoters associated with 12 fragments (utilising DMAP data). Analysis of gene body differential methylation identified 91 genes associated with 121 individual differentially methylated cytosines and 31 genes associated with 31 fragments containing methylated cytosines. Functional pathway enrichment analysis with a FDR <0.05 identified 7 functional pathways through analysis of MethylKit identified genes, and 23 functional pathways through analysis of DMAP identified
The 16 genes associated with the regulatory regions identified by clusters of differential methylation largely falling into either immune or metabolic/mitochondrial related functions. Further gene body analysis identified a number of enriched functional pathways including a number of immune, metabolic and particularly neurological related functions. Together the pattern of DNA methylation in patients implicated components of a number of systems that may be differentially methylated and therefore potentially differentially regulated compared to a healthy population. Particularly the large number of enriched neurotransmitters and neuropeptide reactome pathways identified by DMAP genes implicate an irregular stimulation of the HPA axis through the ‘Stress Centre’ (Paraventricular nucleus), a link between an irregular neuroendocrine response to stress and the stress sensitivity of ME/CFS patients. Overall this work shows specific changes in ME/CFS methylation with compelling links to the pathophysiology of the diseas
Augmenting anti-tumour T cell responses using innate-like T cell ligands
No full textImmunosurveillance is critical for the detection and elimination of malignant cells. Activated CD8+ T cells are fundamental to anti-tumour immune responses due to their ability to specifically target peptide antigens, including neoantigens, derived from tumour cells, and eliminate tumour cells in response.
The activation of naïve CD8+ T cells by antigen presenting cells (APCs) requires presentation of peptide antigens alongside co-stimulatory molecules. APCs upregulate co-stimulatory molecules in response to additional immunostimulatory signals that are not provided by peptide alone. Therapeutic peptide vaccines often attempt to provide these signals by incorporating adjuvants, molecules that enhance an immune response, which activate the APC and lead to enhanced cross-presentation of the exogenously-applied peptide to CD8+ T cells. However, two large phase III cancer vaccine trials failed to demonstrate clinical efficacy, raising the possibility that current adjuvant strategies are insufficient to drive potent anti-tumour CD8+ T cell responses.
This thesis examines whether molecules that activate innate-like T cells can serve as adjuvants to stimulate CD8+ T cell responses with anti-tumour activity, when chemically conjugated to antigenic peptides. In particular, the anti-tumour activity of a new aminobisphosphonate (ABP)-peptide conjugate vaccine was assessed. ABPs inhibit the mevalonate pathway, leading to the accumulation of a compound that activates a subset of human innate-like T cells called, Vγ9Vδ2 T cells. These vaccines enhanced both Vγ9Vδ2 T cell, and peptide-specific CD8+ T cell responses in human cell cultures in vitro. However, the CD8+ T cell response was independent of Vγ9Vδ2 T cell activity, suggesting an alternative mechanism was involved in the adjuvant activity. In support of this, these vaccines induced T cell responses in mice, which completely lack Vγ9Vδ2 T cells, and these responses were sufficient to delay tumour progression in murine models of melanoma and lung carcinoma.
Investigation into the cell-types responsible for the anti-tumour activity revealed responses were independent of the classical cross-presenting APC subset, conventional type 1 dendritic cells (cDC1s), and required a phagocytic CD11c+ APC subset outside of the spleen. Unexpectedly, vaccine activity was also dependent on CD1d and activated NKT cells in vivo. This was not a direct effect of ABP activity, as free ABPs failed to activate NKT cells in vivo. Further assessment raised the possibility that a contaminating particle or macromolecule was responsible for the NKT cell stimulatory activity. Interestingly, the required APC subsets differed from vaccines designed to rely on NKT cell activity, and NKT cells were neither activated nor required for the activity of the ABP-peptide vaccines in human peripheral blood cell assays. Further dissection of the mechanism of these vaccines was confounded by batch-to-batch variability of ABP-peptide conjugate vaccines, requiring modification to the manufacture and testing strategy in the partner chemistry laboratory.
Another class of conjugate vaccines that activate NKT cells had already been assessed in models of melanoma and lung cancer, using model or viral peptides. To extend the applicability of these findings, I sought to assess this concept in a model of HER2+ breast cancer (4T1.2-HER2). This model extends the NKT cell activating conjugate work to a different mouse strain (with lower NKT cell frequency and different NKT cell phenotype), a relevant human tumour-associated antigen (TAA), and to a different tumour model. I demonstrated that NKT cell activation can enhance CD8+ T cell responses against HER2 in vivo, and showed that this glycolipid-HER2 vaccine prevented lung colonisation by 4T1.2-HER2 tumour cells in a metastatic model of breast cancer, providing evidence that NKT cells can adjuvant immune responses against an antigen of translational relevance in breast cancer.
In summary, this thesis first demonstrates that a new class of ABP-peptide conjugate vaccines can drive peptide-specific CD8+ T cell responses independently of the innate-like T-cells it was designed to stimulate, and likely via mevalonate pathway blockade. I show that ABP-peptide vaccines can elicit anti-tumour efficacy in vivo independently of classical cross-presenting APCs, although additional mechanistic work was hindered by manufacturing issues with the ABP-peptide vaccines. Alternative vaccine design strategies are proposed. Second, I show that an existing class of innate-like T-cell-stimulating conjugate vaccines can be successfully employed in a mouse strain that had not previously been used, against a clinically-relevant human TAA, and in a breast cancer model, widening the scope of disease models for conjugate vaccine investigation. I conclude that the concept of conjugate vaccines that target the mevalonate pathway is a promising means of stimulating immune responses against cancer
Finding without searching: A theological engagement with the conversion narratives of young people in Canterbury, New Zealand
No full textWhile academic projects investigating religious conversion are not uncommon, specifically New Zealand-based work on this subject is rare. Moreover, examinations of religious conversion come from a variety of academic disciplines. A discussion of conversion to Christianity from a theological perspective offers a lens through which individual experiences can be understood, thus deepening the body of knowledge that exists within Christian theologies of conversion. A focus on the conversion experiences of young people means that this project makes a meaningful contribution to current theologies of Christian youth ministry. Problematically, the absence of such knowledge in church settings can lead to discussions of conversion that are ill-informed and largely based on anecdotal evidence and conjecture. In my own experience as a former youth pastor in an evangelical church, I heard many Christians share their perspectives on how and why secular young people might decide to become followers of Jesus, and the discussion of these issues motivated the re-design and modification of the ministries of the local church. The present project aims to provide a greater body of data to aid both academic and ecclesial understanding of how and why secular young people are coming to faith in Christ in New Zealand today.
Three sub-questions are used in this project as a means of investigating facets of the conversion experiences of young people: how secular young people might best engage with a church or Christian youth group; how spiritual experiences function in conversion; and the question of the nature and duration of the conversion process. The primary body of data for this project comes from my interviews with thirty-two young adults in Canterbury, New Zealand, each of whom had converted to Christianity in their adolescent years. In every case, these participants’ parents were not practising Christians at the time of their children’s conversions. I used a process of inductive thematic analysis to analyse the interview data. The themes that emerged from the collected data shed light on all of the three sub-questions. In addition, an unexpected finding emerged in the data analysis process. I called it “the match,” and this finding is discussed in a separate chapter.
Analysis of the interview data led to unique and valuable findings related to each of the three sub-questions. For those I interviewed, the church or youth groups were experienced as a place of connection, where key relationships and a supportive, warm environment were experienced as something deeply significant, and even counter-cultural. Spiritual experiences evoked a wide variety of personal consequences in the lives of those I interviewed, and some of these were not entirely positive or expected. I heard how many participants struggled with the reactions of their parents, the various emotions they experienced during their conversion journeys, as well as the doubts and questions that accompanied this time for some. Also, most of those I interviewed experienced conversion as a process that took months or years to complete, although three participants described more punctiliar experiences.
The key unforeseen finding, “the match,” relates to the way that many participants described moments in their conversion journeys where they encountered an unexpected degree of congruity between one of their own emotional or practical needs and something that they encountered in the Christian world. Many participants were quite surprised by this congruity. In fact, analysis of the interviews indicates that they found what they were not looking for at church or youth group. This indicates something as to the relative social position of the church in New Zealand today, as well as how religion in general is perceived in this largely secular nation. Implications from this and other findings are offered at the end of this thesis. These implications can inform both the academy and the Christian world, in that they reveal key dynamics of the relationship between the church and society, between young people and local expressions of Christianity, and between God and those who are not explicitly embarking on a religious search
Intra-individual variability of reaction time and subclinical psychosis
No full textClinical and epidemiological studies have indicated that elevated intra-individual variability (IIV) of reaction time (RT) is a trait phenomenon that indexes vulnerability for a number of clinical conditions, including schizophrenia. Persons classified as at-risk of developing psychotic disorder also exhibit increases in IIV, which has led to suggestions that IIV may represent a potentially useful risk marker for psychosis. However, many aspects of this relationship remain unstudied. My aim in presenting this thesis and its component studies was to determine the robustness of the relationship from IIV to two manifestations of schizophrenia liability—psychotic-like experiences (PLE) and schizotypy. In Chapter 2, the predictive validity of IIV for PLE during adolescence was assessed using birth-cohort data. Elevated IIV on a stop-signal task at 15 years of age predicted suspected or definite PLE at 18 years of age, with stronger associations for frequent and severe classifications of PLE. Elevated IIV at age 15 also predicted the presence of more persistent PLE. There were no associations between any measures of IIV at age 13 and PLE classifications or trajectories. Chapter 3 investigated whether elevations in IIV were stronger for PLE or schizotypy, and whether relationships were due to affective dysregulation. Increases in IIV were more strongly associated with PLE than schizotypy, to a greater extent for complex than simple RT tasks. Associations between IIV and PLE did not appear to be due to affective distress. In two studies presented in Chapter 4, I sought to determine whether cognitive control mediated the relationship between IIV and subclinical psychosis. Here, mediation depended on whether self-report or performance-based measures of cognitive control were used. In Study 1, there were consistent relationships between the assessed constructs of self-reported executive dysfunction, schizotypy, and IIV. Self-reported executive dysfunction appeared to mediate the relationship between IIV and schizotypy. In Study 2, elevations in IIV were associated with poorer performance on an executive task battery, and endorsement of PLE. However, cognitive control was not associated with PLE occurrence, nor did it mediate the relationship between IIV and risk status. Throughout the thesis, IIV did not appear to be consistently related to specific expressions of subclinical symptoms. Overall, these findings suggest that IIV is somewhat uniquely able to index liability to psychosis and may represent an interface between cognitive functioning and psychotic symptoms. However, its utility as a clinical marker appears limited
Same same, but different? Cycling and e-scootering in a rapidly changing urban transport landscape
No full textThis paper explores whether e-scooters can be considered similar to cycling in terms of their demographic appeal and skills required. Building on a social practices approach, we hypothesise that e-scootering and urban cycling may appeal to a similar demographic and require similar competencies. We draw on data from a 2019 survey of users and non-users of e-scooters. Respondents are not more likely to use an e-scooter if they have cycling experience. E-scooters seem to appeal to a broader demographic than cycling. Users are more likely to be young, able, males. Cycling experience is not associated with e-scooter competence.Peer Reviewe
A Last Glacial Maximum to Present Paleoenvironmental Investigation of Port Pegasus, Stewart Island, New Zealand
No full textAlmost all modern-day estuaries evolved during the Holocene and contain sedimentary sequences that preserve the evolution of these coastal environments. Incised-valley fill sequences in estuaries often contain facies that illustrate the transition from terrestrial to marine conditions during post-glacial sea-level rise. The timing of sea-level rise and inundation can be constrained by dating these transitions, and geochemical characterization of the facies exposed in sediment cores provides information about the ways in which sea-level incursion has altered the sediment deposition and carbon accumulation in these environments. Coastal margins are known to be hot spots of carbon accumulation and burial and important components of the global carbon cycle. However, more information is needed to fully understand carbon sequestration processes, rates, and variability, particularly as sea-level begins to rise again after the Holocene still stand (7.5-7.3 ka).
The location of this study, Port Pegasus, is an incised valley estuary located on the southeast margin of Stewart Island, New Zealand, at 47°S. Multibeam bathymetric surveys in combination with tide and catchment data are used to characterize Port Pegasus as a drowned valley, mixed energy estuary with low fluvial input and sediment depocenters within its back basins, and seismic surveys are used to identify and interpret the stratigraphic fill as a transgressive sequence. Five sediment cores sample terrestrial to marine flooding surfaces and sedimentary depocenters and are analyzed for physical properties, paleomagnetic parameters, elemental data, and bulk carbon and nitrogen concentrations and stable isotopes. Radiocarbon ages date the terrestrial to marine transition, identified using geochemical data, and the flooding of Port Pegasus at -22 m to 11.6-11.1 ka. Carbon accumulation rates show that zones of high carbon accumulation shifted from a terrestrial depocenter in the central basin of the inlet with an accumulation rate of 10 g C m-2 yr-1 to the present-day marine depocenters in the isolated back basins with an average rate of 19 g C m-2 yr-1, suggesting that sea-level incursion had a significant influence on carbon accumulation dynamics in the estuary. The source of the organic carbon has also changed; the underlying facies shows a clear abundance of terrestrial organic matter, whereas all Holocene and modern sediment is dominated by marine organic matter. Analysis of back basin sediment cores demonstrates that Port Pegasus may be a promising new location for paleoclimate reconstructions of Southern Hemisphere westerly wind variability and that cores extracted closer to the fluvial inputs in the estuary will likely contain terrestrial signals that vary with the magnitude of freshwater flux. This study gives insights into New Zealand Holocene sea-level rise and the potential role of meltwater pulses in coastal estuarine formation as well as the significant effect of sea-level transgression on coastal carbon storage dynamics and the important role that drowned valley systems such as Port Pegasus play in the global carbon cycle
Exploration and discovery: Learning at a science centre
No full textFree-choice learning provides the majority of human learning over the course of a lifetime. Since interactivity developed in science centres fifty years ago, hands-on learning has been spreading itself all around the world, with a current estimated visitation of 300 million people each year. This research investigated the impact of visiting a science centre on three aspects of scientific literacy: scientific knowledge, self-beliefs in science, and science engagement. While there is research around these constructs, the literature investigating the effect of a single visit on them using matched measurements before and after that visit is sparse. Data were collected with mixed methods, including pre-post surveys, interviews, and focus groups at the Otago Museum’s science centre. The science centre is located in Dunedin, New Zealand, and recently underwent a major renovation. Before the redevelopment, 224 respondents filled out a pre-post survey. After the redevelopment, three more surveys were administered, collecting another 1,099 paired responses.
A brief ‘formal’ multiple-choice test proved to be useful in assessing knowledge without alienating visitors. A new self-reporting instrument was developed, called fluency in scientific concepts; results were closely related to scientific knowledge. Both constructs increased steeply with age from eight years old to early twenties and then changed only moderately. Also, both scientific knowledge and fluency increased significantly after one visit to the science centre, irrespective of age. Interviews with museum staff and two focus groups with children contributed to the research by identifying specific science exhibit characteristics that relate to visitor engagement and learning in all generations.
Self-efficacy and self-concept are related self-beliefs that behave differently. Self-reported self-efficacy increased dramatically with visiting the science centre, while self-concept remained stable. Although expected, these results have rarely been tested. Given its stability, self-concept was used to test a new alternative to Likert-type scales. A Visual Discrete Scale was developed for this research; it is characterized by being completely visual, with no labels. The Visual Discrete Scale proved to be a viable alternative to Likert-type scales with potentially more sensitivity to small changes in self-beliefs. A gender gap was detected in knowledge and self-beliefs. Evidence in this study did not support the idea of the gap being related to females’ low-confidence. Instead, this study’s results suggest that science engagement was originally low for female respondents, perhaps related to this study’s focus on physics
Post-Disaster Recovery Efforts in Japan and New Zealand: What Worked Well? What Hasn't?
No full textNatural disasters present significant threats to the infrastructure, economy, and most importantly, people. Land-use planning is fundamental to post-disaster management and the effects are often reflected in the efficiency of the policies and regulations in place. Post-disaster management in Japan is arguably regarded as the state of art, and this research seeks to evaluate the planning frameworks and policies that were developed in response to the 2011 Earthquake and Tsunami in Tōhoku, Japan. Disaster management comes in four stages: Mitigation, Preparedness, Response and Recovery. Mitigation measures can include a soft or hard approach. A softer approach can include maintaining the protective natural features such as sand dunes, wetlands and forests. A harder approach ranges from building retaining walls on hillslopes to sea walls in the coastal environments. Preparedness on the other hand, include educating the communities in case of an emergency; and responses to a disaster are often short-term measures such as providing food and water. This research intends to focus on the final stage of disaster management- recovery. The recovery stage involves responses to not just the physical destruction, but also the social and economic repercussions from natural disasters. This requires major financial and scientific inputs from a range of sectors, including the national government. A comparison of the disaster management frameworks between Japan and New Zealand is carried out to determine whether these policies have been effective in practice and to identify where improvements can be made to disaster management in New Zealand following the 2016 Kaikōura Earthquake