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    Adjunctive intravenous then oral vitamin C for moderate and severe community-acquired pneumonia in hospitalized adults: Feasibility of randomized controlled trial

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    Patients hospitalised with community acquired pneumonia (CAP) have low peripheral blood vitamin C concentrations and limited antioxidant capacity. The feasibility of a trial of vitamin C supplementation to improve patient outcomes was assessed. Participants with moderate and severe CAP (CURB-65 ≥ 2) on intravenous antimicrobial treatment were randomised to either intravenous vitamin C (2.5 g 8 hourly) or placebo before switching to oral intervention (1 g tds) for 7 days when they were prescribed oral antimicrobial therapy. Of 344 patients screened 75 (22%) were randomised and analysed. The median age was 76 years, and 43 (57%) were male. In each group, one serious adverse event that was potentially intervention related occurred, and one subject discontinued treatment. Vitamin C concentrations were 226 µmol/L in the vitamin C group and 19 µmol/L in the placebo group (p < 0.001) after 3 intravneous doses. There were no signficant differences between the vitamin C and placebo groups for death within 28 days (0 vs. 2; p = 0.49), median length of stay (69 vs. 121 h; p = 0.07), time to clinical stability (22 vs. 49 h; p = 0.08), or readmission within 30 days (1 vs. 4; p = 0.22). The vitamin C doses given were safe, well tolerated and saturating. A randomised controlled trial to assess the efficacy of vitamin C in patients with CAP would require 932 participants (CURB-65 ≥ 2) to observe a difference in mortality and 200 participants to observe a difference with a composite endpoint such as mortality plus discharge after 7 days in hospital. These studies are feasible in a multicentre setting

    Microsclerotia production in Sclerotinia sclerotiorum: A potential bioherbicide for Californian Thistle and Giant Buttercup : A thesis submitted in partial fulfilment of the requirements for the Degree of Master of Science at Lincoln University

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    The plant pathogen, Sclerotinia sclerotiorum, was further investigated as a potential bioherbicide targeting the problematic weeds Cirsium arvense (Californian thistle) and Ranunculus acris (Giant buttercup). Previous research has found that S. sclerotiorum can be effective at controlling both weeds with bioherbicide work primarily focused on solid substrate production of fungal mycelium, which has proven cost-prohibitive to scale up. The primary objective of this research was to investigate whether S. sclerotiorum could produce microsclerotia (MS) in liquid fermentation. Liquid fermentation is more cost-effective and scalable than solid substrate production. MS are small and resilient fungal propagules with characteristics such as desiccant tolerance and shelf stability, that make them attractive as propagules to be used as an active ingredient for a bioherbicide. Although MS production has been demonstrated for other species of fungi, it has not previously been reported for S. sclerotiorum. The suitability of MS incorporated into a S. sclerotiorum bioherbicide formulation was additionally assessed. Six S. sclerotiorum isolates (S36, S37, GGB1, GGB2, G57 and G64) were screened for their suitability for future bioherbicide development. The growth of the isolates was compared under a range of illumination (12 hr photoperiod or 24 hr darkness) and temperature (15 °C, 20 °C and 25 °C) conditions. Their pathogenicity on excised leaves of C. arvense (provenances G20 and G27) and R. acris (haplotypes A, A2, G and J) was compared. GGB2 was found to be the fastest growing isolate and was one of the most pathogenic isolates on both host species. This isolate is a potential candidate for future research. Seven liquid media with varying compositions were screened for their ability to induce MS formation with S. sclerotiorum isolate S36. A single media was identified that resulted in MS production, yielding 4.5 x 103 MS per mL after 14 days of fermentation at 300 rpm. Bioassays using formulations of these MS as inoculum on excised leaves of C. arvense and R. acris initially showed promising results. MS inoculum caused lesions on both species covering a large proportion of the leaf area and resulted in lesions significantly larger than those from a sclerotia inoculum (P < 0.001). Replications of the bioassay resulted in no lesions with the MS formulations, which led to further investigation of the formulation and drying process. The survival of the MS at each step of the formulation process was examined. The survival of the structures decreased dramatically when dried to below 30% moisture. Adjusting the fermentation time and carrier used did not improve MS viability after the drying step. Microscopy of the MS ultrastructure indicates that the drying process may be causing damage to the hyphal cell membranes, resulting in lysis of the cell and potentially causing low viability. Production of S. sclerotiorum MS has been demonstrated for the first time. Despite the inconsistency of MS of S. sclerotiorum to survive drying and cause infection, MS remain a promising propagule for a future bioherbicide. Optimization of the fermentation and formulation should be the focus of future work. If reliable production of desiccant tolerant MS of S. sclerotiorum can be achieved, this would present an opportunity to enable the sustainable management of C. arvense and R. acris

    ‘The worst time of year in Rome for the Olympics’: Lessons and legacies in healthcare from the 1960 Olympic Games

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    The provision of medical support for athletes during the Olympic Games has been a feature of each Olympic event. Prior to 1960, medical services were largely utilitarian in nature, frequently relying on military medical services and focused on providing only the essential medical support to athletes, support staff and spectators during the games. However, the appointment of Professor Luigi Gedda to lead the Medical and Scientific Committee for Rome led to an expansion of healthcare services beyond routine clinical delivery, to focus on an extensive and controversial research and education programme during the games. Subsequently, the games were confronted by a range of novel clinical scenarios, including the presence of intense heat during competitions, the transmission of infectious disease among athletes, the rapidly expanding use of drugs by athletes and the death of an athlete following competition. This paper utilises archival documents and contemporary sources to critically review the nature, effectiveness and impact of the healthcare provided at the 1960 Olympic Games

    Exploring spatial land use typologies for housing + food production: A Canterbury case study

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    Peri-urban areas are vitally important to the function and value of our settlements, communities, ecology and economies, particularly in a world where the localisation of the food supply chain is increasing in priority as natural disasters, pandemics, severe weather events, and human-induced conflicts amplify the lack of resilience in our often long and complex food systems. The peri-urban zone of Aotearoa, once a key contributor to the local foodshed is facing unprecedented pressure from land use change. Planning for the future of these areas is challenging, with planning policy and practice often contested, and functional solutions elusive. Aotearoa New Zealand lacks research into innovative spatial land use possibilities for the co-existence and mutual benefit of accommodating both people and food production within peri-urban zones – spatial typologies that re-prioritise food production as a vital part of the peri-urban zone. Based on an extensive survey and design critique workshop with Greenfield residents and peri-urban Growers operating with the Selwyn District, as well as interviews with Mana Whenua and archival mahinga kai mapping, this research has developed a set of spatial land use typologies specific for the peri-urban zone of Aotearoa New Zealand, addressing the question - How can landscapes for both people and production prosper within peri-urban Aotearoa through innovative spatial design, reconnecting New Zealanders with whenua and food

    Colour characterization of two‐year old Pinot noir wines by UV‐Vis spectrophotometry and tristimulus colourimetry (CIELab): Effect of whole bunch or grape stems addition

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    Pinot noir wines were made with inclusion of different amount of whole bunches or grape stems: destemmed grapes only (DS), 30% whole bunch (WB30), 60% whole bunch (WB60), 100% whole bunch (WB100), and destemmed grapes with 100% stems added back (DS100). Wines were analysed using modified Somers assay and CIELab method at the end of fermentation and after two years bottle ageing. CIELab analysis showed that DS100 was significantly different from all other treatments at both sampling points, and whole bunch addition treatments (except of WB30) only showed significant colour difference compared to DS treatment after bottle ageing. Total anthocyanins were significantly reduced in stem inclusion treatments at the end of alcoholic fermentation, but after two years bottle aging, only DS100 treatment showed significantly lower anthocyanins than DS treatment. Stem inclusion treatments significantly increased tannin concentration. Total anthocyanins and tannins in wines reduced by 69-71% and 24-31% respectively after bottle ageing

    Epigenetic modifications impact metabolite production and lifespan in yeast

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    Epigenetics have been shown to play a crucial role in regulating gene expression during the aging and immune response processes, with changes in epigenetic marks being linked to age-related diseases and inflammatory responses. Recently it has been revealed that S-adenosyl-l-homocysteine can extend the lifespan of the budding yeast Saccharomyces cerevisiae by mimicking caloric restriction. In this present study, we aimed to activate the production of S-adenosyl-l-homocysteine by S. cerevisiae through introducing epigenetic changes as a result of exposure to benzoic acid, a known epigenetic modifier. The impact of this on metabolite production was evaluated using LC-MS/MS. The study successfully activated and measured an overproduction of S-adenosyl-l-homocysteine (SAH) in yeast previously exposed to benzoic acid and led to lifespan extension. The link between the aging process and immune responses in yeast was further explored in the study. The production of SAH was downregulated while several inflammatory response metabolites were upregulated in aging cells. The upregulation of inflammatory response metabolites with their inherent anti-viral and antimicrobial activities could potentially be valuable for use in human health applications. By contrast, in cells with higher lifespans these inflammatory metabolites were downregulated. This finding supports the concept that aging leads to higher levels of histone methylation and acetylation, which in turn cause the production of immune response metabolites and inflammation. By contrast, it appears that lower levels of histone methylation and acetylation as seen in healthy cells, can increase production of metabolites responsible for lifespan extension, such as SAH. In summary, this study provides insights into the molecular mechanisms involved in lifespan extension and the role of metabolites in regulating aging in yeast. The research sheds light on the interplay between metabolism, epigenetics, immunity and aging and contributes to the growing field of metabolomics

    Proposal and extensive test of a calibration protocol for crop phenology models

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    A major effect of environment on crops is through crop phenology, and therefore, the capacity to predict phenology for new environments is important. Mechanistic crop models are a major tool for such predictions, but calibration of crop phenology models is difficult and there is no consensus on the best approach. We propose an original, detailed approach for calibration of such models, which we refer to as a calibration protocol. The protocol covers all the steps in the calibration workflow, namely choice of default parameter values, choice of objective function, choice of parameters to estimate from the data, calculation of optimal parameter values, and diagnostics. The major innovation is in the choice of which parameters to estimate from the data, which combines expert knowledge and data-based model selection. First, almost additive parameters are identified and estimated. This should make bias (average difference between observed and simulated values) nearly zero. These are “obligatory” parameters, that will definitely be estimated. Then candidate parameters are identified, which are parameters likely to explain the remaining discrepancies between simulated and observed values. A candidate is only added to the list of parameters to estimate if it leads to a reduction in BIC (Bayesian Information Criterion), which is a model selection criterion. A second original aspect of the protocol is the specification of documentation for each stage of the protocol. The protocol was applied by 19 modeling teams to three data sets for wheat phenology. All teams first calibrated their model using their “usual” calibration approach, so it was possible to compare usual and protocol calibration. Evaluation of prediction error was based on data from sites and years not represented in the training data. Compared to usual calibration, calibration following the new protocol reduced the variability between modeling teams by 22% and reduced prediction error by 11%

    Climatic conditions affect shoot flammability by influencing flammability‐related functional traits in nonfire‐prone habitats

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    Plant flammability is an important driver of wildfires, and flammability itself is determined by several plant functional traits. While many plant traits are influenced by climatic conditions, the interaction between climatic conditions and plant flammability has rarely been investigated. Here, we explored the relationships among climatic conditions, shoot-level flammability components, and flammability-related functional traits for 186 plant species from fire-prone and nonfire-prone habitats. For species originating from nonfire-prone habitats, those from warmer areas tended to have lower shoot moisture content and larger leaves, and had higher shoot flammability with higher ignitibility, combustibility, and sustainability. Plants in wetter areas tended to have lower shoot flammability with lower combustibility and sustainability due to higher shoot moisture contents. In fire-prone habitats, shoot flammability was not significantly related to any climatic factor. Our study suggests that for species originating in nonfire-prone habitats, climatic conditions have influenced plant flammability by shifting flammability-related functional traits, including leaf size and shoot moisture content. Climate does not predict shoot flammability in species from fire-prone habitats; here, fire regimes may have an important role in shaping plant flammability. Understanding these nuances in the determinants of plant flammability is important in an increasingly fire-prone world

    Sensuous atmospheres of landscape and memory

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    The sensuous qualities of atmospheres are intimately tied to the landscape’s potency as a place of memory. More than any other design discipline, landscape architecture is bound to place, and the place specificity of atmospheres is a critical component of the experiential landscape. And more than its close ally, architecture,landscape is spatially and temporally fluid. Landscape architecture is rooted to the ground, it is highly responsive to light, moisture, climate, and the intangibilities of memory. Sensuous atmospheres in the landscape offer potential realms for memory. Memory is aligned with a range of senses, of which smell and taste are the most vivid (as with Proust’s madeleines), augmented by sound, sight, and touch. Memories tend to invoke emotions. Past traumatic events, losses of people and places, float in atmospheres of melancholy.Invocations of fondness and longing might flicker and shimmer in nostalgic atmospheres. From a landscape architectural perspective all of this raises intriguing questions about the degree to which an atmosphere can be designed. Can affective atmospheres of nostalgia and melancholy be infused into landscapes? Two projects are explored to probe the possibilities of intentionally invoking atmospheres, exploring how could the landscape be ‘tonalised’ in a particular way. Aspects of diffusion and attunement provide the basis for thinking about shared emotion, and how an intentional (i.e.designed) landscape of memory could invoke a collective affective atmosphere. The first project, The Storm Cone, is by British artist Laura Daly. The project is an augmented reality app which provides an immersive audio-visual experience for the user, through invoking the form and sounds of an English bandstand from the early twentieth century – a quintessentially British landscape atmosphere. I consider the atmospheric potency of the app through my experience of using it in a park in my home city in New Zealand, and explore questions related to how augmented reality might be related to atmosphere, drawing on some of the work related to installation art, augmented reality and sound, as well as landscape-related perspectives. Can a landscape atmosphere be generated through an augmented reality app, and does it provide the setting for a shared emotional experience of a past memory. Can an atmosphere be experienced asynchronously by different app users at different times? The second project is one I have been working on for a number of years in my role as a landscape architect and memorial designer. The project is a memory landscape for the Pike River Mine, which exploded in 2010, killing 29 men. Rather than an ‘accident,’ the site remains a crime scene, as the cause of the explosion is investigated by the police. There is a palpable atmosphere that emanates from the site. Not only from the circumstances of the deaths, but also from a deeper history of local Māori and their own tragic connection to this site. The design of the memorial landscape explores how communication with the dead men has generated a kind of affective dimension to the site, a shared emotion for visitors, an atmosphere. The atmosphere is augmented by the particular qualities of light,moisture and vegetation at the site, which is deep in dense, damp, rainforest. The temporal and spatial fluidity of the landscape raises questions over how, as designers, we can amplify the atmosphere of the site, to intensify visitors’experiences. Through spatially extrapolating the mine into the open air, can we emplace visitors into a ‘force field’ of charged atmosphere? Can the aural aspects of saying the dead men’s names, and becoming attuned to the forest’s sounds offer an atmosphere of loss

    Improving accuracy of quantifying nitrate removal performance and enhancing understanding of processes in woodchip bioreactors using high-frequency data

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    Woodchip bioreactors have gained popularity in many countries as a conservation practice for reducing nitrate load to freshwater. However, current methods for assessing their performance may be inadequate when nitrate removal rates (RR) are determined from low-frequency (e.g., weekly) concurrent sampling at the inlet and outlet. We hypothesised that high-frequency monitoring data at multiple locations can help improve the accuracy of quantifying nitrate removal performance, enhance the understanding of processes occurring within a bioreactor, and therefore improve the design practice for bioreactors. Accordingly, the objectives of this study were to compare RRs calculated using high- and low-frequency sampling and assess the spatiotemporal variability of the nitrate removal within a bioreactor to unravel the processes occurring within a bioreactor. For two drainage seasons, we monitored nitrate concentrations at 21 locations on an hourly or two-hourly basis within a pilot-scale woodchip bioreactor in Tatuanui, New Zealand. A novel method was developed to account for the variable lag time between entry and exit of a parcel of sampled drainage water. Our results showed that this method not only enabled lag time to be accounted for but also helped quantify volumetric inefficiencies (e.g., dead zone) within the bioreactor. The average RR calculated using this method was significantly higher than the average RR calculated using conventional low-frequency methods. The average RRs of each of the quarter sections within the bioreactor were found to be different. 1-D transport modelling confirmed the effect of nitrate loading on the removal process as nitrate reduction followed Michaelis-Menten (MM) kinetics. These results demonstrate that high-frequency temporal and spatial monitoring of nitrate concentrations in the field allows improved description of bioreactor performance and better understanding of processes occurring within woodchip bioreactors. Thus, insights gained from this study can be used to optimise the design of future field bioreactors

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