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Intervertebral Disc Tissue Engineering: An Investigation of Chitosan/PCL Scaffolds using 3D-printing and Melt-electrowriting Technology
No full textIntervertebral disc (IVD) degeneration is one of the major causes of lower back pain a highly common health condition that greatly effects a person’s quality of life. Due to an increasing aging population and change in lifestyles, there exists high demand for novel treatment strategies for damaged IVD. Moreover, the current treatment strategies focus on pain alleviation and restoration of mechanical properties, and do not address the underlying biological issues.
Researchers have focused on IVD tissue engineering (TE), which aims to restore biological and mechanical functions by regenerating or replacing the damaged discs. To date, there is no adequate tissue-engineered IVD (TE-IVD) available, therefore a more suitable option needs to be explored.
The current project aims to develop a TE-IVD utilising a naturally derived polymer, chitosan, in both the annulus fibrosus (AF) and nucleus pulposus (NP) regions of the IVD in order to encourage tissue integration and regeneration.
A poly--caprolactone (PCL)/chitosan blend mimicking the AF-lamellae structure was explored using melt-electrowriting (MEW) technology, which combines the advantages of three-dimensional (3D) printing and electrospinning to fabricate micro-fibrous scaffolds with controlled architecture. PCL is commonly used for AF and displays good mechanical properties with a slow degradation rate, but has poor cellular adhesion. Chitosan was chosen to impart bioactivity to the structure. Due to chitosan’s high water absorbing capacity, a chitosan-based hydrogel was also developed to mimic the structural characteristics of the native NP.
The MEW parameters were optimised to fabricate the MEW scaffolds in order to mimic the AF structure, and their physical and biological properties characterised. The biological activity of the MEW scaffolds was also investigated in vitro using human bone marrow-derived mesenchymal stem cells within a newly developed cell infiltration test. This cell infiltration test protocol will be useful for future TE research. The developed chitosan hydrogel mimicked the native NP gelatinous structure and demonstrated adequate compressive mechanical properties, degradation behaviour as well as high biocompatibility.
Results demonstrated the addition of chitosan increased the cellular activity of the MEW scaffolds in a concentration dependent manner. The chitosan hydrogel fabricated was also found to be suitable for use in the NP region. The NP hydrogel and AF scaffolds showed encouraging tissue regenerative capability by addressing both mechanical and biological issues, and when combined could potentially act as a TE-IVD to replace the native IVD in its entirety. Moreover, the results obtained in this project not only demonstrated the high-potential of these developed TE-IVDs, but also provided validation of the use of the GeSiM 3.1 Bioscaffolder for the development of 3D tissue-engineered constructs
Hope, Self-Denial and the Love of God: Towards a Kierkegaardian Perspective on Self-Condemnation-Unto-Death
No full textFew events have the potential to be as destructive for individuals, groups, and communities as suicide. By drawing on the theology of Søren Kierkegaard, this article aims to elucidate a perspective which contains theo-ethical, psychological, and pastoral import for those contemplating, or faced with, the tragic prospect of guiltmotivated suicide. This is principally done by highlighting the nature and centrality, for Kierkegaard, of God’s unconditional and unchanging love in Christ. The pertinent offshoots of this for the present article are twofold: firstly, every individual is, at all times, held in being by divine love; secondly and correlatingly, the task of every human being of conforming his or her will to the selflessness of God cannot be foreclosed—put differently, perpetual love entails perpetual hope. Despite not usually being regarded as a theologian whose work is relevant to public issues, I thus claim that Kierkegaard provides resources for a robust position against individual self execution out of guilt.Peer Reviewe
The Effect of rs77275268 on Gene Expression at the Transcriptional Hub at 6q25.1
No full textBreast cancer is a prevalent and harmful disease that is divided into subtypes based on tumour characteristics. The main subtype is oestrogen receptor positive (ER+), accounting for approximately 80% of all breast carcinomas. ER+ breast cancer presents with overexpression of the oestrogen receptor (ER) and is commonly treated with hormone therapies that block the ER from responding to oestrogen stimulus, theoretically blocking growth of the cancer. However, in many cases, this treatment is unsuccessful and the mechanisms behind this resistance remain elusive. Genetic variation in a transcriptional hub around the ER gene (ESR1) at 6q25.1, including three upstream genes (ARMT1, CCDC170 and RMND1) has been correlated with increased genetic susceptibility. Therefore, characterisation of the gene expression at this region is important for future breast cancer therapies.
SNP variants at the 6q25.1 region have been studied through genome wide association studies and have been associated with increased breast cancer susceptibility. The SNP rs77275268 within this hub is present in the human genome as either a cytosine (C) to thymine (T) variant within a CpG island of a known CTCF binding region. This SNP could affect the methylation status of this site potentially altering CTCF binding in this region. CTCF proteins are transcriptional regulators that bind to specific sites of the DNA and have been found to be affected by DNA methylation. CTCF can play a role in 3D chromatin structure and therefore altered binding of the protein can influence the expression of genes such as those in the ESR1 transcriptional hub. This project therefore aimed to elucidate the expression of the genes at the transcriptional hub with the rs77275268 SNP C and T variants.
Expression and correlation of these genes at 6q25.1 (ESR1, CCDC170, ARMT1 and RMND1) in relation to the T variant of the rs77275268 SNP was analysed using quantitative real-time PCR (qPCR). These results showed co-expression of ESR1 and CCDC170 and also RMND1 and ARMT1 supporting the hypothesis that CTCF binding could be altered at this genomic region. Chromatin immunoprecipitation (ChIP) was then utilised to determine potential changes in binding at the SNP dependent on the variant. This was limited by the fact that only one biological replicate was generated and therefore initial results produced are not conclusive, however suggest a change in CTCF binding dependent on the SNP variant present.
This project also sought to produce an alternative ER+ breast cancer cell line containing the rs77275268 SNP T variant for further CTCF investigation through CRISPR editing. However, these attempts were unsuccessful with the rate of homology directed repair to insert the specific mutation occurring at a very low rate.
In summary, this study demonstrated that the rs77275268 SNP T variant changes how the genes at the transcriptional hub 6q25.1 are co-expressed. Preliminary investigation suggests that the altered expression could be influenced by changes in CTCF binding resulting in a change in chromatin looping. Further attempts to create a SNP edited ER+ breast cancer cell line with higher constitutive CTCF binding are needed to confirm this hypothesis
Addressed by the word: The practical, pastoral, and eschatological anthropology of Eduard Thurneysen
No full textEduard Thurneysen (1888-1974) was a Swiss Reformed minister and theologian. He is known both for his foundational work in dialectical theology alongside Karl Barth and for his kerymatic pastoral theology as outlined in his 1946 book "Die Lehre von der Seelsorge". While most of Thurneysen reception has focussed either on his relationship to Karl Barth and early dialectical theology or on his practical technique of his pastoral care, I am interested primarily in the theological-anthropological assumptions that underpinned Thurneysen's pastoral praxis.
In this thesis, I address two questions: "What was Thurneysen's understanding of being human as it developed over the course of his life?" And, "What are the implications of his theological anthropology for the praxis of the church?" The thesis is divided into two main parts that correspond respectively to each question. In part one, I trace the chronological development of Thurneysen's theological anthropology. In part two, I explore further three key threads that emerge from part one: the practical, the pastoral, and the eschatological. I unpack these three aspects with the aid of three interlocutors: Ray Anderson, John Swinton, and Jürgen Moltmann.
For Thurneysen, the human being is a responsible person addressed by the living Word of God. The living God addresses the human being in the midst of the faith community, calling him or her into new reconciled relationship with God and others. Consequently, being human is a practical and pastoral reality that must be lived, drawing one into God's coming future and the realisation of God's good purposes for human life together
Biosorption of heavy metals from drinking water using fruit and vegetable peels
No full textHeavy metals in drinking water are a serious global concern and efforts are underway to develop sustainable decontamination techniques. The present project was developed with an aim to prepare biosorbents for treating household drinking water. Six natural fruit and vegetable peels (FVPs), namely, apple peel (AP), banana peel (BP), cucumber peel (CP), kiwifruit peel (KP), orange peel (OP) and potato peel (PP) were immobilised on sodium alginate (SA) beads and used as biosorbents for the removal of one metalloid and six heavy metal ions, namely, arsenic (As V), cadmium (Cd II), chromium (Cr VI), copper (Cu II), mercury (Hg II), lead (Pb II) and nickel (Ni II) from drinking water. Batch experiments were performed to study some of the main parameters that influence the biosorption process, namely, contact time, pH, biosorbent concentration, initial ion concentration and temperature, using solutions prepared by spiking the ions in distilled deionised laboratory water. A comparison of the biosorption efficacies of the various FVP beads was made, and biosorption was studied in spiked real drinking water collected from a mine region in New Zealand. The surface of the beads was imaged using scanning electron microscopy coupled with energy dispersive spectroscopy, and the concentration of ions in solution was measured using inductively coupled plasma with a mass spectrometer detector. The applicability of kinetic models such as film diffusion, pore diffusion, pseudo-first order, pseudo-second order and Elovich equation was examined using the biosorption data. A novel effort to study isotherms and thermodynamics in non-equilibrium conditions was made using the Probability Isotherm theory proposed for biochemical reactions. The suitability of isotherm models such as Langmuir, Freundlich, Temkin and Dubinin-Radushkevich to non-equilibrium data was examined. The nature of the binding of the ions to the surface of the beads and the energy changes involved were determined from the parameters calculated in these models. The results showed that the roughness and heterogeneity of the surface was related to the biosorption efficacy of the beads. Therefore, FVP beads were better performing relative to the SA beads. CP and KP beads had the highest biosorption capacities, followed by AP and BP beads. The beads also showed different affinities for the ions. While 70-90% of the divalent metal ions were removed simultaneously from solution, the biosorption of As and Cr anions was less than 35%. Although KP bead biosorbed the highest percentage of Cr (~34%), it also showed the second-lowest Hg removal percentages (~53%) after AP bead (~50%). In contrast, CP bead removed ~90% Cd and Hg, but had the lowest Cu removal (~72%) from solution. BP bead showed the highest efficient in removing Cu (~87%) among all the beads. Biosorption of Pb was the lowest among all the divalent ions and OP bead had the lowest removal (~57%) among the beads. On the other hand, PP beads and BP beads biosorbed the highest percentage of Pb (~74%) from solution, although PP beads were the least effective for the simultaneous removal of heavy metal ions in general. All the beads biosorbed approximately 15%, 90% and 70-80% of As, Cd and Ni, respectively, from cocktail solution. The beads successfully removed metal ions in the drinking water pH range. The use of more number of beads in solution resulted in an increase in biosorption percentage but also a corresponding decrease in the biosorption capacity of the beads. In contrast, at higher ion concentrations (up to 15 mgL-1), there was a decrease in the biosorption percentage and a corresponding increase in the biosorption capacity of the beads. The temperature of the solution played a significant role in the biosorption process and affected the uptake of the ions to various degrees. Furthermore, the presence of co-ions suppressed the biosorption of individual ions and this was observed both in laboratory and real drinking water. In conclusion, CP and KP beads showed the most promising removal of heavy metals from drinking water, but no bead could significantly biosorb As. Appropriate modifications to the beads will be required to increase heavy metal ion biosorption when many competing natural ions are present in drinking water. If that is achievable, then this technology could revolutionise drinking water treatment processes especially in developing countries where low cost purification systems are needed
Alpine Fault fluid composition and transport in proximity to the fault, using analyses of out-crop samples and gases entrained in drill fluids
No full textThe chemistry of fluids and gases within fault zones can provide information about their sources/origins, flow rates and paths, and further fluid-rock interactions along those paths. New Zealand’s tectonically active Alpine Fault Zone is an ideal system within which to study fluids because there is a wealth of supporting prior research about it. Furthermore, globally there are very few systems that are similarly both late in the seismic cycle, and known to rupture in large events. Phase 2 of the Deep Fault Drilling Project (DFDP-2) aimed to drill to, and through the Alpine Fault at ~1 km depth to obtain information about its physical state and structure before it next ruptures. Online gas analysis (OLGA) was employed to monitor gases (N2, O2, Ar, CO2, CH4, He, H2, hydrocarbons, and Rn) entrained in the circulating drill mud, which were derived from crushed rock at the drill bit, and from permeable layers within the drilled formation. 33 complimentary offline samples collected at the time of drilling over the depth range 236 to 892 m were later analysed for standard % of gas by volume, and He and carbon isotopes. He isotope data were also acquired from 14 core samples of outcropping Alpine Fault mylonites from four different locations. In both surface and offline DFDP-2B samples, 3He/4He ratios of bulk rock showed R/Ra values of 0.46 (±) and 0.57 (±), increasing with proximity to the fault. This indicates interaction with mantle derived fluids at depth, and supports a previous suggestion there is a present day fluid flux from the mantle along the fault. However, hangingwall and footwall He ratios differ sufficiently to support previous suggestions based on Sr isotopes that the Alpine Fault is an effective barrier to cross-fault fluid flow. OLGA data were commonly of low quality due to various drilling-related disturbances, or equipment problems. However, some useful data were collected. The most notable signal in OLGA was variation in Rn, inferred to reflect interception of particularly permeable horizons in the surrounding formation
A critical analysis of tourism taught master's education
No full textCan tourism education contribute to a better (tourism) world, in which business and societal needs are evenly prioritised? Global society faces myriad and unprecedented challenges, many of which, directly or not, are linked to tourism. Therefore, producing graduates who are able to work effectively in tourism whilst also taking responsibility for tourism’s socio-cultural and environmental impacts is increasingly considered to be important. Arguably, offering a curriculum that balances vocational education (that which may help equip students with technical skills and knowledge) and liberal education (that which may connect students to societal issues) may be one way to help produce such graduates. However, with the neoliberal higher education environment taking hold in various (inter)national contexts, institutions are increasingly encouraged to focus attention on the private interests of individual students. Along with this comes a perceived demand for vocational education linked to immediate employability. Consequently, students may be largely educated for ‘business as usual’, rather than being educated for a ‘public good’ and/or to promote change.
Against this backdrop, the aim of my research was to better understand the outlook of and for tourism education in contributing to a better (tourism) world. The context for my research was tourism taught Master’s (TTM) programmes, a particularly important context given that tourism’s future leaders, planners and decision-makers are being forged, in ever greater numbers, within these programmes. Conducted over two phases, and utilising a combination of qualitative content analysis and case study, my research investigated:
- The aims, objectives and content of TTM programmes being offered around the world, as stated in online prospectuses (Phase one; qualitative content analysis).
- Staff and students’ experiences of TTM education (Phase two; case study).
Phase one of my research demonstrated that most TTM programmes appear to prioritise vocational learning, focussing largely on equipping students with the necessary skills and knowledge to work efficiently within the tourism industry. In contrast, liberal learning – that which encourages critical reflection on the relationship between the individual and society, ergo the betterment of society – appears much less of a priority. Phase two of my research, however, suggested that a TTM programme that is able to balance vocational and liberal learning opportunities can play a powerful role in changing students’ thinking and behaviour. It does so primarily by helping students appreciate the practical relevance/importance of a liberal education. Further, some TTM graduates that have emerged from such a programme are actively involved in changing the (tourism) world for the better. Therefore, it seems, TTM programmes such as this, that dare to challenge ‘business as usual’ by going beyond narrow vocational parameters, do have the potential to contribute, in profound and lasting ways, to a better (tourism) world. Despite this, however, internal pressures linked to neoliberal externalities, including students’ perceived desire for more ‘practical’ learning, are prompting academic staff and curriculum planners to incorporate more vocational learning opportunities at the possible expense of liberal learning opportunities. The main recommendation from my research, therefore, is that finding additional ways to help students more readily appreciate the practical, or ‘use’, values(s) of their learning may offer some solution to ease the problematic tensions within TTM education
Design and evaluation of a mobile decision support system for screening neurodevelopmental disorders
No full textNew Zealand has the highest rate of youth suicide in the developed world. Young persons with ADHD and ASD, amongst other neurodevelopmental disorders, are at greater risk for depression, suicidal ideation, and suicide attempts than their typically developing peers. The early detection and treatment of neurodevelopmental disorders significantly improves the symptomatology and life outcomes of affected individuals. Gaining timely access to specialist mental health clinicians is difficult. This process is made more difficult for children who do not present with overt signs of severe and persistent psychological distress and therefore are not deemed to be ‘high risk’, including the majority of children with ADHD and ASD. Consequently, the diagnosis of children with neurodevelopmental disorders is substantially delayed and/or the responsibility to identify and/or treat falls on clinicians (and non-clinicians) such as general practitioners, general paediatricians, nurses, and educators who may not have the background to have developed complex schemas in this domain.
The aim of the present thesis was to develop and test decision support systems that employ different reduced-processing design principles. This was done to determine which principles were effective in assisting individuals who do not possess complex clinical schemas, to diagnose children with neurodevelopmental disorders, in the absence of training and practice with the systems. Several manipulations of decision support system interfaces were developed and tested across different populations of prospective diagnosticians. Across four studies, participants were randomly assigned one of several diagnostic-aids, which differed in their capacity to reduce-processing demands, to assist with clinical diagnosis in a simulated context.
Study One: The researcher tested the efficacy of the DSM-5 and two alternate diagnostic-aids that employed one or two reduced-processing design principles that pertained to the arrangement (facilitated the simultaneous acquisition of information) and/or volume (restricted content preconfigured by two clinicians who specialise in neurodevelopmental disorders) of diagnostic information in assisting naïve diagnosticians to diagnose two patients in two separate filmed clinical interviews (both 20-minutes in length). Participants who used the tablet-based diagnostic-aid that employed two (but not one) reduced-processing principles achieved significantly greater diagnostic accuracy scores, with the vast majority of participants in this group correctly (and more efficiently) diagnosing both a seven-year-old with ADHD and a 3-year-old with ASD. There were no significant differences in diagnostic accuracy or response latency between participants who used the DSM-5 and participants who used the diagnostic-aid that employed one reduced-processing principle (restricted, preconfigured content).
Study Two: The paradigm from Study One was adopted in Study Two to test the efficacy of the DSM-5 and the diagnostic-aid that employed two reduced-processing design principles in assisting novice diagnosticians (Psychology Master’s students) to diagnose both ASD and ADHD. Participants who used the ‘reduced-processing’ diagnostic-aid achieved significantly greater diagnostic accuracy scores compared to participants who used the DSM-5, with the vast majority of participants in the ‘reduced-processing’ diagnostic-aid group making two correct diagnoses.
Study Three: The paradigm from Studies One and Two was adopted in Study Three to examine the extent to which the interactive mechanism of the ‘reduced-processing’ diagnostic-aid to record categorised symptoms of perceived relevance to the patient, influenced diagnostic performance amongst naïve diagnosticians. Three versions of the ‘reduced-processing’ diagnostic-aid, which were identical in content volume and arrangement, were tested: An interface with an interactive mechanism to record categorised symptoms (the ‘Categorisation Interface’ that was used in Studies One and Two), an interface with an interactive mechanism to record uncategorised symptoms (‘Highlighting Interface’), and an interface with no recording mechanism (‘Passive Interface’). Participants who used the ‘Categorisation Interface’ achieved significantly greater diagnostic accuracy scores (and lower response latencies for correct diagnoses of ASD) compared to participants who used the DSM-5, ‘Highlighting Interface’, and ‘Passive Interface’, with the vast majority of participants in the ‘Categorisation Interface’ group making two correct diagnoses. There were no significant differences in diagnostic accuracy or response latency between the DSM-5, ‘Highlighting Interface’, and ‘Passive Interface’ groups.
Study Four replicated and extended Study Three. The ASD scenario from the previous studies was adopted in Study Four to examine whether the ‘Categorisation Interface’ needed to be used ‘during + after’ the clinical footage (as it was in Studies 1-3), or if it could also be used ‘after’ the clinical footage to improve diagnostic accuracy. Participants who used the ‘Categorisation Interface’ immediately following the clinical footage were just as accurate (but significantly slower) in diagnosing ASD as participants who used the ‘Categorisation Interface’ both during and immediately following viewing the footage.
Conclusion: A decision support system that is structured to facilitate the simultaneous acquisition of a restricted set of preconfigured critical diagnostic features, with the additional capacity to record categorised symptoms of perceived relevance to the patient, was found to assist individuals who do not possess highly developed (or complex) clinical schemas to accurately and efficiently diagnose both ASD and ADHD, in the absence of training and practice with the system. This research has important practical implications for the early detection of neurodevelopmental disorders
Unbundling Litigation Services in New Zealand: Where to next?
No full text‘Unbundled legal services’ and ‘unbundling’ are terms that can be used to describe the practice of providing a limited set of legal services in a litigation matter, accompanied by the expectation that the client will proceed on behalf of themselves on all other aspects of the matter. This paper considers the importance of unbundling in New Zealand to increase access to justice and suggests reform measures to enable more unbundled legal services
Rural Areas within Twenty Territorial Local Authorities, Compared
No full textThis is the fourth report in a series sponsored by the Taranaki Bishop’s Action Foundation (BAF). The series aims to build understanding of the changes occurring in rural in New Zealand, with particular attention to the Taranaki region.
This fourth report examines the rural districts, rural centres and minor urban areas of another ten territorial local authorities and compares them to the rural areas of the ten territorial local authorities compared in report two. The ten territorial local authorities selected include case study areas for a Department of Geography project at Otago University being conducted under the auspices of the National Science Challenge (NSC) Building better homes, towns and cities: Ko ngā wā kāinga hei papakainga