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Natural aggregate resources in Fiji: Mineralogical and geochemical characteristics and its implications for their quality
Get PDFNatural aggregates are a low commodity, high-value material. It plays a major role in creating, maintaining, and enhancing the infrastructure in society. With this comes the responsibility to select the best possible aggregate based on the physical and chemical compositions. Even though Fiji has an extensive distribution of natural aggregates over a range of geologic settings, not all of them are readily accessible or available for use. A systematic investigation of different chemical and minor physical properties of natural aggregates was undertaken in this study. For the purpose of this study, the term aggregates have been applied to deposits of bedrock or naturally occurring rocks.
This thesis aims to characterise the mineralogical and chemical properties of rocks (natural aggregates) from various lithologies. A total of 5 sites were investigated on Viti Levu, Fiji Islands. Seventeen different samples were collected from these sites which represented nine different lithologies (trachyte basalt, basalt, basanite, andesite, monzonite, granite, syenite, limestone, and sandstone). Their physical and structural features were determined in the field and the predictive aggregate grade was determined based on weathering and strength of the rock units. The mineralogy and the chemical composition were determined using bulk geochemistry analysis using XRF and XRD techniques.
The whole-rock geochemistry distinguished the different rocks studied. A total of 17 rock samples from functional and prospective hard rock quarry sites were studied. These different rock types are from volcanic, plutonic, and sedimentary origins. Out of the seventeen samples, eleven rock samples were characterised as a satisfactory aggregate grade based on the physical characteristics with four of these classified as a strong natural aggregate by means of rock strength parameters. The different feldspar and the pyroxene members were identified using the an-ab-or and wo-en-fs plots. The clay minerals were identified based on the XRD analysis. A total of eleven samples showed a substantial amount of illite, kaolinite, chlorite, and montmorillonite mineral content.
The physical and structural data collected during this study categorises eleven rock samples as satisfactory aggregate grades based on their physical characteristics. In terms of strength, only four are classified as strong. The laboratory results provide in-depth knowledge of the mineralogical and chemical components. These data help in categorising these rocks in terms of their possible use in the different stages of construction
Preclinical Assessment of Experimental Therapeutics for CLN6 Batten Disease
Get PDFNeuronal ceroid lipofuscinoses (NCLs; Batten disease) are a group of thirteen genetically heterogenous lysosomal storage diseases that, collectively, are the most common cause of fatal neurodegeneration in children. CLN6 Batten disease (CLN6 BD), also known as LakeCavanagh disease, is a late infantile onset variant of the NCLs caused by loss-of-function mutations in the CLN6 gene. Mutations in both alleles of the gene result in classic NCL symptoms – blindness, epilepsy and progressive cognitive and motor decline – as well as characteristic pathophysiological features such as premature and accelerated neuronal cell death, chronic neuroinflammation and the intracellular accumulation of autofluorescent storage material in lysosomes. As a monogenic, inherited and fatal disorder, CLN6 BD is an excellent candidate for experimental gene therapy.
Several preclinical and clinical trials of gene therapy have been conducted for a range of genetic disorders, including several NCL variants, and these have shown promising results. Subsequently, a clinical phase I/II CLN6 BD trial was initiated by the Gray Foundation and Amicus Therapeutics in 2016. This trial, which is ongoing at the time of writing, has produced optimistic safety and tolerance interim data. But, past experience with clinical gene therapy trials for several other genetic and metabolic disorders suggests that any improvements will not be curative. For this reason, the Gray Foundation began to investigate complementary treatments that might augment the therapeutic efficacy of gene therapy in CLN6 BD. This project used a naturally occurring murine model of CLN6 BD (the Cln6nclf mouse) to investigate the efficacy of two small molecule (drug) therapies – gemfibrozil and cannabidiol (CBD) – alone and in combination with adenovirus associated virus (AAV2/9)-
mediated gene therapy, as protection against the CLN6 behavioural phenotype. Specifically, Cln6nclf and C57Bl/6 (control) mice received a unilateral intracerebroventricular (i.c.v) injection iv of gene therapy (an AAV2/9 vector expressing hCLN6 under the control of a chicken β-actin
gene promoter) or saline (1x PBS) on post-natal days 0-2. Post-weaning, mice were dosed orally (every second day) with either gemfibrozil, CBD, a combination of the two drug therapies or a vehicle solution. Behavioural testing (ataxia phenotyping and rotarod performance) was conducted at 6, 9 and 12 months of age.
Testing of over 500 animals determined that the oral administration of gemfibrozil, CBD, or a combination of the two drugs did not make any consistently significant improvements to untreated or gene-therapy treated Cln6nclf mouse behaviour. The study was successful, however, in reaffirming the apparent efficacy of i.c.v gene therapy in protecting against CLN6 BD behaviour in Cln6nclf mice (of both sexes), with no significant reduction in behavioural scores, when compared to healthy controls.
This study represents the first long-term, large-scale preclinical study of this particular combination of therapies for CLN6 BD. It provides a solid foundation for further work searching for a comprehensive and curative treatment regimen for CLN6 BD
Reply to "Should we use the multidimensional model of sleep health to assess the outcomes of sleep health promotion interventions? A commentary on: Do sleep interventions change sleep duration in children aged 0-5 years?" by Professor Reut Gruber
No full textSystematic review of mydriatics used for screening of retinopathy in premature infants
Get PDFIntroduction Routine retinopathy of prematurity eye examinations are an important part of neonatal care, and mydriatic medicines are essential in dilating the pupil for the eye examination. There are concerns about the level of evidence for efficacy and safety of these mydriatic medicines.
Objective This review evaluates both efficacy and safety evidence of mydriatics used during the retinopathy of prematurity eye examination.
Method Systematic literature review.
Results There is limited evidence guiding clinical practice for safety and efficacy of mydriatics. The majority of publications are underpowered and with an unclear to high level of bias. There are a wide variety of mydriatic regimens evaluated for efficacy and safety, and multiple regimens are associated with case reports.
Conclusions Current international guideline seems unnecessarily high, especially when the reviewed literature suggest that lower doses are effective, albiet from underpowered studies. The lowest effective combination regimen appears to be phenylephrine 1% and cyclopentolate 0.2% (1 drop). Microdrop administration of this regimen would further increase the safety profile, however, efficacy needs to be assessed.Peer Reviewe
Towards Porous Carbon-Rich Frameworks Assembled Through Three-Dimensional π-Stacking
No full textPorous materials have sparked the interest of many researchers because of their extensive surface area and absorptive properties. Depending on their pore size and atomic composition, applications for such materials are vast, ranging from catalysis and wastewater treatment to gas storage and drug delivery.
Reticular chemistry is the widely followed blueprint for synthesis of porous framework materials, which involves combining well-defined nodes with linker units. The various methods for assembly of these building blocks are often separated into distinct research areas, such as metal-coordinate bonding, covalent bonds or non-covalent interactions.
Supramolecular-organic frameworks (SOFs) is the least explored branch and is predominantly comprised of frameworks that utilise hydrogen bonding to drive framework assembly (HOFs). This work strives to synthesise a porous material that self-assembles through ordered π- stacking interactions in three dimensions. Tetrahedral phosphonium nodes bearing four tert- butyl-functionalised hexa-peri-hexabenzocoronene (HBC) arms were predicted to assemble into face-to-face dimers via intermolecular π-interactions. Many HBCs form dense, extended columnar structures in the solid state due to strong π-stacking, but HBCs substituted with peripheral tert-butyl groups adopt a more limited π-stacking dimer motif. The dimerised π- stacking at four corners of the large phosphonium tetrahedron could drive the formation of a porous, diamondoid framework.
Synthetic approaches toward the target molecule were first tested by forming a phosphonium salt with one HBC arm to develop the best route, while simultaneously assessing the stability of the phosphonium core unit. The initial synthetic pathway was focussed on divergent expansion out from the phosphonium core. However, the testing revealed that in order to prevent degradation of the tetrahedral core under some reaction conditions, an integrated divergent/convergent approach was most suited to form the target molecule. The best synthetic results were produced from tests which incorporated a phenylene spacer unit between the phosphonium cationic core and the HBC.
Phenylene and biphenylene spacer-containing tetra-HBC phosphonium salts were successfully synthesised and subjected to a range of recrystallisation conditions in order to obtain a single crystal structure for X-ray diffraction analysis. Unfortunately, the biphenylene spacer-containing tetra-HBC compound exhibits poor solubility in common organic solvents, which makes forming crystals challenging. The derivative with phenylene spacers is soluble in common organic solvents, but despite numerous recrystallisation attempts, crystals big enough for analysis were not forthcoming
Gaming for empathy: Encounters with the Other in digital narratives
Get PDFDifferent mediums can dramatically alter how stories are told, how characters are represented, and ultimately, how we engage and respond as an audience. Narratives told through a digital medium are no exception, as these works can depict compelling narratives with elements such as animation, audio, and three-dimensional (3D) narrative environments. In fact, some of these narratives in digital media have been referred to as "empathy games," which denotes that these works can facilitate empathy for characters, including characters that represent a marginalized Other. The notion that a narrative in digital media can foster empathy for the Other prompts two problems which also emerge in literary studies: promoting empathy through narratives is not a controllable effect, and narratives cannot represent the Other without the risk of establishing or reinforcing stereotypes. This project takes up these issues by assessing four narratives in digital media, and this comprehensive analysis demonstrates that narratives in digital media offer a means to address these obstacles and ethical barriers.
My project draws on the theoretical work of scholars, including feminist theorist Rosi Braidotti, philosopher Jacques Derrida, and post-colonial scholar Gayatri Spivak, who have proposed concepts and methods that work to disrupt hegemonic ideology that fixedly defines the Other as an oppressed subject. Drawing on their work, I reveal that their concepts and methods can take shape in digital media and destabilize the hegemonic ideology that otherwise informs a player's narrative interpretation and perception of the Other represented in the story. Additionally, I refer to the work of scholars such as Suzanne Keen to consider other obstacles in fostering narrative empathy and show that narratives in digital media provide methods to overcome some of these barriers. This critical examination reveals that narratives in digital media can address the long-standing ethical challenge of representation of the Other and overcome other obstacles that emerge on the pathway to fostering empathy for the Other
Online Legal Information Self-Help in Aotearoa: An agenda for action
Get PDFThis report reviews international experience in the development of online legal information and self-help (OLISH) provided by government, community organisations, and social enterprises. It uses this experience to examine how OLISH might best be deployed in Aotearoa New Zealand to help narrow the justice gap. It also examines the context and processes that have driven the development of OLISH in other jurisdictions and how this experience might apply in Aotearoa
Alleviating Death Anxiety in Epicureanism
Get PDFEradicating the fear of death is a central concern in Epicurean philosophy. As hedonists, the Epicureans seek to pursue pleasure and avoid pain in order to achieve a life of eudaimonia. The fear of death is viewed as a particularly damaging form of mental pain, and the Epicureans go to great lengths to demonstrate that it is, in fact, irrational.
The ‘fear of death’ is a relatively broad term. It not only encompasses the fear of being dead, but also the fear of dying, the fear of mortality, and the fear of premature death. How adequately the Epicureans address each of these fears has been the subject of much debate. I argue that the Epicureans do successfully recognise and abolish these four strands of anxiety. They use a network of arguments to combat the multi-faceted nature of the fear of death. A close examination of these arguments reveals that they are deeply entrenched in the Epicureans’ underlying physical and ethical theories. The individual arguments each form one part of a holistic attempt to remove the fear that is seen to obstruct a life of pleasure. As such, the arguments must not be viewed independently, but rather as a collective whole. I demonstrate that the Epicurean efforts to alleviate death-related concerns are comprehensive, cogent, and internally consistent. Therefore, when Epicureanism is embraced as a whole, the fundamental goal of a pleasurable life that free from the fear of death is entirely attainable
Lumbar Anterior Column Spine Surgery Techniques, Complications and Outcomes
Get PDFLumbar anterior column spine surgery uses minimally invasive anterior and lateral retroperitoneal techniques for the insertion of wide footprint interbody devices to provide indirect neural decompression and correct deformity.
The utility and reliability of co-registration of isotope bone scans with CT and MRI to identify spinal pathology, location of pain and facilitate surgical planning was investigated.
We undertook prospective studies on the learning curve for lateral lumbar interbody fusion, indication for standalone cages, success of indirect decompression, influence of facet arthropathy, factors causing cage subsidence and techniques to mitigate the risk of subsidence.
The clinical outcomes, fusion rates and complications of anterior lumbar interbody fusion were evaluated with the benefits of brief intraoperative heparinisation. Anterior versus lateral interbody fusions were compared at 2-year follow-up.
We investigated the benefits of performing anterolateral lumbar interbody fusion in obese patients positioned lateral decubitus over multiple levels in a single position.
Recommendations for performing these available lateral, anterior and anterolateral interbody fusions at each spinal level for different indications were compared.The techniques and a treatment algorithm to guide the need for supplemental fixation in anterior, lateral and anterolateral interbody fusions were discussed. Bone graft substitutes to avoid or augment iliac crest autograft harvest were evaluated. The fusion rates, clinical outcomes, complications and cancer risk of bone morphogenetic proteins were determined over a ten-year period then compared prospectively with a new calcium phosphate bone substitute alternative.
Advanced applications of these minimally invasive techniques include anterior resection of symptomatic developmental lumbo-pelvic pseudoarthrosis and the lateral approach for thoracolumbar corpectomy and thoracic discectomy.
Motion preservation adjacent to an anterior column fusion, by either anterior or lateral artificial disc replacement, were discussed with indications, complications, revision strategies and salvage options.
Guidelines were provided to assist hospital administrators and surgeons for the purchase and applications of currently available image guidance, navigation and robotic systems to improve the accuracy of pedicle screw placement
Discoveries from the alpine daisy Celmisia viscosa: unique diterpenes and flavones, and variation within the species
Get PDFThis thesis focuses on the natural product chemistry of the native Alpine daisy, Celmisia viscosa. Previous work on C. viscosa has shown the presence of the diterpenes epimanool and the rare halimadienol, also present were these compounds with a new glycoside attached. There were indications of these and related compounds in other New Zealand Celmisia species. This study aimed to investigate variation among Celmisia and to isolate and characterise the major novel compounds associated with variation. Using C. viscosa, a repeatable method of CDCl3 extraction and NMR and GC analyses from small quantities of leaf material has been established. This allowed for the investigation of chemical variation using portions of stored botanical voucher specimens, extracts of which were subjected to Principal Component Analysis (PCA). Variation among eight species of Celmisia was investigated, with results indicating that C. viscosa stands out, having generally the highest secondary metabolite concentrations and intraspecific variation.
Investigation of variation within a C. viscosa plant sourced from End Peak, Harris Mountain found the leaves to contain the highest concentration of diterpenes. Further investigation, of C. viscosa leaves from three plants from the same region indicated only variation in diterpene concentration, not diterpene type. C. viscosa leaf material was sourced from herbaria, giving access to nearly the full geographic range of C. viscosa from different regions around South Island, New Zealand. Results indicated the presence of two distinct chemotypes.
Isolation of the major compounds from each chemotype gave epimanool and the reported epimanool glycoside, 2’,6’-dideoxy-hexopyran-3’-ulose isolated from CHCl3 leaf extracts from the Kakanui Ranges. Halimadienol plus two novel derivatives, halimadienol 4’-acetyl-2’,6’-dideoxy-hexopyran-3’-ulose and halimadienol-4’-hydroxy-2’,6’-dideoxy-hexopyran-3’-ulose were isolated from CHCl3 leaf extracts from the Rock and Pillar Ranges. Halimadienol has been also reported from Jungermannia infusca and Plagiochila barteri, but it was not fully characterised. The data herein presents the full characterisation of halimadienol with X-ray crystallography revealing the absolute stereochemistry.
NMR Spectroscopic data indicated halimadienol to be conformationally mobile, but subjecting the compound to 13C NMR at various temperatures failed to give access to the slow exchange conformation. However, computational modelling revealed two significant conformers, the major of which matched that of the crystal structure. 2D NMR and spectroscopic data for the halimadienol 4’-acetyl-2’,6’-dideoxy-hexopyran-3’-ulose, previously isolated, but not published, is presented herein. Isolation of halimadienol-4’-hydroxy-2’,6’-dideoxy-hexopyran-3’-ulose gave the opportunity for the absolute stereochemistry of the glycoside moiety to be deduced using Mosher ester analysis. Halimadienol-4’-hydroxy-2’,6’-dideoxy-hexopyran-3’-ulose was acetylated to further confirm the stereochemistry.
Halimadienol and epimanool have quite different retention indices and times with halimadienol eluting earlier from GC-FID-MS column. This behaviour suggested that the halimadienol could be thermally degrading upon injection onto the GC column. A study of the behaviour of these compounds upon injection onto a column at various temperatures failed to verify this assertion, so halimadienol was chemically dehydrated, with the products being reinjected onto GC, thereby refuting the hypothesis.
Three novel acylated trimethoxyflavones: 8-(3”-methylbutanoyl), 5-hydroxy-5,7,4’-trimethoxyflavone, 8-(2”-methylbutanoyl), 5-hydroxy-5,7,4’-trimethoxyflavone and 8-(2”-methylpropanoyl), 5-hydroxy-6,7,4’-trimethoxyflavone were discovered in a bulk CHCl3 extract of leaves from the Rock and Pillar Ranges. Characterisation of these compounds was achieved by 2D NMR, comparison to model compounds and X-ray crystallography. Subsequent structural elucidations of a mixture of four novel acylated dimethoxyflavones: 8-(2”-methybutanoyl), 5,4’-dihydroxy-6, 7-dimethoxyflavone; 8-(3”-methybutanoyl), 5,4’-dihydroxy-6,7-dimethoxyflavone; 8-(2”-methybutanoyl), 5,7-dihydroxy-6,4’-dimethoxyflavone; 8-(3”-methybutanoyl), 5,7-dihydroxy-6,4’-dimethoxyflavone and a mixture of two novel acylated monomethoxyflavones: 8-(2”-methylbutanoyl),5,7,4’-trihydroxy-6-methoxyflavone and 8-(3”-methylbutanoyl),5,7,4’-trihydroxy-6-methoxyflavone were made using the trimethoxyflavones as model compounds. X-ray crystallography of 8-(2”-methylbutanoyl),5,7,4’-trihydroxy-6-methoxyflavone confirmed the proposed structures. An ethanol extract of C. viscosa leaf material from Mount Harris gave the two major dimethoxyflavones; 8-(2”-methybutanoyl), 5,4’-dihydroxy-6,7, dimethoxyflavone; 8-(3”-methybutanoyl), 5,4’-dihydroxy-6,7, dimethoxyflavone in a 2:1 mixture allowing for partial 2D NMR assignment of both compounds. Analysis of the seven other species of Celmisia indicated novel flavone profiles and analysis of the full range of C. viscosa leaf extracts by HPLC indicated the presence of flavone chemotypes.
While this work has increased the chemical knowledge of C. viscosa a range of further work remains for both the species and the genus. Further analysis of the chemical variation of viscid species of Celmisia regionally may uncover further species exhibiting chemotypic variance, while bulk extraction may lead to the discovery of other novel diterpenes. More within site leaf extract analysis may uncover differing chemotypes within plants in proximity. If more bulk C. viscosa from other regions is sourced, extraction and isolation may provide evidence of more novel diterpene derivatives. Ecological studies with halimadienol and epimanool may provide insight around the function of these compounds. Assessment of the contents of trichomes, found on the flowers of C. viscosa, would confirm whether these structures contain flavones or diterpenes