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Enhanced Advance care planning and life Review Longitudinal Intervention (EARLI): Protocol for a cluster randomized controlled cross-over trial of life story work and facilitated advance care planning among older Australian adults in community settings
No full textBackground: Advance care planning (ACP) is potentially helpful for older adults, however, the rate of uptake in community aged care settings is low. Previous pilot studies suggest that holistic, person-centered ACP approaches may be effective for older adults who experience functional impairment but do not necessarily have life-limiting conditions with clear prognoses. This paper describes the protocol of a randomized trial to test the effectiveness of combined life story work and facilitated ACP in promoting ACP engagement among older adults receiving community aged care services. Methods: The Enhanced Advance care planning and life Review Longitudinal Intervention (EARLI) trial is an open-label, cross-over, cluster randomized controlled trial with 12 participating aged care organizations in New South Wales and Western Australia. Participants are aged 65 years or older, receiving home care services and capable of providing informed consent at initial recruitment. Recruitment occurs across a two-year period, with study sites randomized to receive the four-session intervention in the first or second year (or a single session ‘active control’ condition). Primary outcomes are participant-reported ACP engagement and ACP documentation in the aged care client record 12 weeks post-recruitment. Secondary outcomes include measures of decisional conflict, anxiety and depression, meaning-based coping and relationship quality. Analysis will take an intention-to-treat approach. Conclusion: This trial tests a novel method of reaching older adults using a holistic, person-centered approach to promoting ACP engagement. Enhancing ACP engagement may reduce decisional conflict, minimize hospital admissions and improve outcomes for people and their families. ANZCTR Trial Registration ID: ACTRN12622001399785.</p
Direct ink writing of gradient shear-stiffening elastomer for enhanced toughness and impact resistance
No full textShear-stiffening materials have garnered significant attention due to their inherent ability to rapidly respond to changes in strain rate. However, conventional studies on these materials exhibit limited mechanical performance and insufficient structural design, hindering applications in material science and smart mechatronics. Inspired by the gradient structure of a squid beak, this study uses a direct-ink-writing (DIW) technology to develop a novel gradient shear-stiffening elastomer (GSSE). Comprehensive characterizations were conducted to optimize the printability of the shear-stiffening elastomer under various testing conditions, including rheology, compression, and tension. Additionally, the toughness and impact resistance of the elastomer were systematically investigated. It is demonstrated that the biomimetic GSSE exhibits enhanced flexibility, efficient energy dissipation, and outstanding impact resistance. Consequently, this work advances the field of shear-stiffening elastomers for diverse applications by leveraging the gradient structure design strategy to achieve superior mechanical performance under complex loading conditions.</p
Impact of Combination Therapies on Graft-versus-Host Disease and Graft-versus-Leukaemia Immunity
No full textAllogeneic haematopoietic stem cell transplantation (alloHSCT) is a curative therapy for haematological malignancies, including leukaemia, that are refractory to conventional chemotherapy and radiotherapy. AlloHSCT aims to generate graft-versus-leukaemia (GVL) immunity, where the alloreactive donor T cells eliminate residual host malignant cells following myeloablation. However, a common and often fatal side effect of this treatment is graft-versus-host disease (GVHD), where these alloreactive donor T cells (graft) recognise the healthy tissues of the transplant recipient (host) as foreign and mount a destructive inflammatory immune response. Despite the use of prophylactic agents, GVHD occurs in 30-60% of patients and results in severe damage to multiple organs including the liver, skin, gastrointestinal tract and lungs. One therapeutic strategy for the prevention of GVHD is the use of post-transplant cyclophosphamide (PTCy). However, while PTCy reduces GVHD occurrence and severity, GVHD still develops in 40-50% of patients and the cellular mechanisms by which PTCy reduces the disease are not fully understood. Additional therapies and a greater understanding of the cellular mechanisms through which PTCy abrogates GVHD are therefore required.Interleukin (IL)-6 is a pleiotropic cytokine with a central role in T cell differentiation and GVHD development. When IL-6 is present with transforming growth factor β, naive T cells develop into T helper (Th) 17 cells, which have been shown to exacerbate GVHD. However, in the absence of IL-6, the same naive T cells develop into regulatory T cells (Tregs), which have a protective role against GVHD. As such, driving the T cell differentiation pathway away from inflammatory Thl7 cells and toward Treg development is a potential strategy for the prevention of GVHD.Chapter 3 of this thesis investigated the effect of tocilizumab (TOC), an anti-IL-6 receptor monoclonal antibody (mAb), combined with PTCy on immune cell engraftment and GVHD development in a humanised mouse model. NOD-scid-IL2Rγnull (NSG) mice were injected intraperitoneally (i.p.) with 2 x 107 human peripheral blood mononuclear cells (hPBMCs) and cyclophosphamide (33 mg/kg) or control diluent on days 3 and 4, then TOC or control antibody (0.5 mg/mouse) twice weekly for 28 days. Combination therapy with TOC and PTCy delayed GVHD onset and increased proportions of human (h) Tregs but did not improve long-term survival outcomes compared to PTCy alone.T cells are involved in GVHD pathogenesis and GVL responses, thus, it is important to ensure that GVHD preventative strategies do not abrogate GVL immunity. Therefore, Chapter 4 investigated the impact of PTCy alone and combined with TOC on GVL immunity to human THP-1 acute myeloid leukaemia cells in a humanised mouse model of GVL immunity. NSG mice were injected i.p. with 2 x 107 hPBMCs followed by treatment with PTCy and TOC (as above), then injected intravenously with 1 x 106 THP-1 cells on day 14. PTCy did not compromise GVL immunity but reduced both the hepatic and splenic hCD4+:hCD8+ T cell ratio. Moreover, PTCy increased the proportions of splenic hCD39+ Tregs and increased both the hepatic and splenic hThl7:hTreg ratio but had no impact on circulating human cytokines. Further, combination therapy with TOC and PTCy did not impact GVL immunity and reduced histopathology in the liver and lung, with minimal impact on T cell subsets and circulating cytokines.Although PTCy can reduce GVHD, the precise cellular mechanisms through which it reduces the disease are not fully understood and high doses are associated with toxicities. Therefore, Chapter 5 aimed to determine whether a lower dose of PTCy can reduce GVHD and to examine the effects of low-dose PTCy on human immune cell subsets, T cell exhaustion, and tissue damage at early and late time points in GVHD development in a humanised mouse model. NSG mice were injected i.p. with 2 x 107 hPBMCs and cyclophosphamide (33, 25 or 10 mg/kg) or control diluent on days 3 and 4. Low-dose PTCy at 10 mg/kg abrogated clinical signs of GVHD with comparable efficacy to high-dose PTCy at 33 mg/kg, with improved survival and delayed GVHD onset. Moreover, proportions of PD-l+hCD4+ and PD-l+hCD8+ T cells were increased by PTCy at 10 mg/kg but not 25 or 33 mg/kg, while proportions of PD-1+ hTregs were increased by PTCy at all doses. Further, proportions of exhausted hCD8+ T cells were increased with 33 mg/kg PTCy, but not lower doses of PTCy.Thl7 cells can exacerbate GVHD, therefore, Chapter 6 investigated the impact of Thl7 cell targeted compounds alone or combined with mafosfamide (MAFOS), an active cyclophosphamide analogue, on the proliferative capacity and proportions of T cell subsets using in vitro proliferation assays. Treatment with 5 μg/mL secukinumab, an anti-IL-17 mAb, had no impact on the proliferation or proportions of the T cell subsets assessed. However, FGIN-1-27 (known to impair murine Thl7 cells) inhibited the proliferation of several T cell subsets involved in GVHD pathogenesis, with the greatest impact on Thl7 cells. Moreover, combining FGIN-1-27 with MAFOS did not have an additive or synergistic effect, with proliferation and subset proportions similar between cells treated with FGIN-1-27 and FGIN-1-27 with MAFOS.Collectively, this thesis demonstrates that combination therapy with PTCy and TOC can reduce GVHD severity while retaining GVL immunity in humanised NSG mice. Furthermore, this thesis shows that a reduced dose of PTCy abrogates GVHD to a similar extent as a higher dose, and further elucidates the impact of PTCy on human immune cell subsets in humanised NSG mice. Finally, this thesis identifies a novel Thl7-targeted compound, FGIN-1-27, as a potential GVHD therapeutic using in vitro proliferation assays.</p
Improving high temperature oxidation resistance via tungsten modification in FeCr2V-based low activation medium entropy alloys
No full textThe high-temperature oxidation behavior of FeCr2VWx (x = 0, 0.1, 0.3, 0.5) low activation medium-entropy alloys (LAMEAs) was investigated in air at 650 °C. Using systematic post-mortem microstructural analysis and in-situ confocal microscopy, the oxidation kinetics were found to follow a parabolic law. Compared to conventional nuclear-grade P91 steel, FeCr2VWx LAMEAs exhibited superior oxidation resistance. The diffusion rate constants of solute elements in the FeCr2VWx alloys were determined to be 0.68, 0.529, 0.522, and 0.538 mg2·cm−4·h−1 for x = 0, 0.1, 0.3 and 0.5, respectively, significantly lower than the value of 0.704 mg2·cm−4·h−1 observed for P91. Notably, the W0.3 alloy demonstrated a 1.35× lower diffusion rate constant than P91. The enhanced oxidation resistance is primarily attributed to two mechanisms: (1) the addition of W increases the melting point of the oxide scales, preventing liquefaction and promoting the rapid formation of a denser, more protective oxide layer, thereby delaying oxidation, and (2) the formation of a WO3 inter-oxide layer, which effectively impedes element diffusion and further improves oxidation resistance.</p
A study on pricing American options under regime-switching model
No full textRegime-switching models gained popularity over the past decade because of their distinctive advantage of modeling different financial market statuses in a discrete manner rather than a continuous manner as in stochastic volatility models. When they are used in option pricing, the clear advantage is that it enables a larger parameter space for models to be calibrated for a specific market dynamics and thus allows a better quantitative risk management in terms of utilizing financial derivatives. However, due to the increased model complexity, the associated computational effort usually increases as well. Therefore, there is a demand for developing approximate option pricing approaches, which can be heavily used in algorithmic trading with their super computational efficiency.This thesis contributes to the problem of pricing American options under regime-switching model. In Chapter 3, a novel computational approach is presented, which can enhance the computation efficiency when the price of an American option under a two-state regime-switching model needs to be numerically computed. Later in Chapters 4-5, a generalized regime-switching model is considered. Several highly efficient formulations based on different integral equation methods are presented, particularly when the number of regimes is large. In Chapter 6, analytical approximations of the American option prices and optimal exercise prices have been investigated, perturbed around a solution to a special case of either identical volatilities for all regimes (equivalently Black-Scholes model) or a short tenor. For both scenarios, an error bond is established for the proposed approximate solution in terms of accuracy. Finally, an illustration is provided in Chapter 7, to explain how the computational results obtained from a regime-switching model are implemented in the pricing of American options in financial practice.</p
Efficient and Robust Models for Trust Evaluation in Open, Dynamic, and Sociable Environments
No full textTrust evaluation is widely used as an assistance for decision-making in sociable environments, such as social networks, sensor networks, web services, e-commerce, Crowdsourcing, Peer-to-Peer (P2P) networks, Internet of Things (IoT), and cloud computing, where entities cooperate to accomplish their objectives. However, due to the open, dynamic and decentralised properties of sociable environments, entities only have a local view of the environment, making it difficult to evaluate other’s trustworthiness based on their limited interaction experiences. In this situation, entities usually search for trusted paths between a source entity and a target entity based on neighbours, which incurs problems of being disturbed by unreliable trust paths and subjective neighbours. Besides, entities will seek information about target entities from third-party advisors, which incurs problems like being misled by subjective advisors and being deceived by dishonest advisors. Overall, there are two challenging problems for trust valuation in sociable environments: 1) uncertainties caused by decentralization and subjective neighbours/advisors; and 2) risks caused by dishonest advisors.</p
Interactions of early exercise rights and exotic barriers associated with certain derivatives
No full textFinancial derivatives are becoming increasingly popular among investors and academic researchers. As research progresses, more attention is being given to the pricing of complex financial derivatives, such as those incorporating early exercise rights and barrier features.If holders have early exercise rights, they possess the right to exercise their financial derivatives before the maturity date, which is a characteristic feature of American-style derivatives. This early exercise feature transforms the pricing of American-style financial derivatives from a linear to a non-linear problem, unlike the pricing of European-style derivatives, resulting in much greater complexity. Moreover, the existence of early exercise rights contributes to a higher price for American-style financial derivatives compared to their European-style counterparts, due to the additional rights granted to the holders.In terms of exotic barrier features, we explore the “hard” and “soft” barrier features in this thesis. The former refers to the activation of the barrier feature when the recorded time of the underlying asset price over or below a predetermined barrier price exceeds a preset strike time. The latter, also known as the “m out of n” days feature, entails the activation of the barrier feature when the underlying asset price has been above or below a predetermined barrier price for “m” days out of the past “n” consecutive trading days before the current trading day. Both the hard and soft features affect the value of financial derivatives because they introduce the possibility of the derivatives becoming worthless or having a predetermined price.Therefore, if a financial derivative combines both of these two features, namely early exercise rights and exotic barrier features, these two features could interact with each other, influencing the price of the financial derivative. Exploring the interaction between these two features is the goal of our thesis, achieved through pricing a couple of particular exotic derivatives, such as American-style Parasian options and convertible bonds with a soft call.Chapter 1 presents the introduction and literature review on options and convertible bonds, followed by the mathematical background in Chapter 2. Then, we determine the price of a Parasian option with a hard window in Chapter 3 and examine how the early exercise right and barrier feature impact the option price. Subsequently, in Chapter 4, we establish the partial differential equation (PDE) for a Parasian option with a soft window, establishing a price relationship between Parasian options with soft and hard windows. Expanding our focus beyond Parasian options, we also consider convertible bonds, which incorporate both early exercise rights and barrier features. Consequently, we derive the price of “one-touch” callable convertible bonds and explore a property of this financial derivative. Detailed insights into this are provided in Chapter 5. Finally, building on the methodology introduced in Chapter 4, we extend our analysis to determine the value of convertible bonds with a “delayed” barrier feature, which is referred to as a soft call, in Chapter 6. Finally, Chapter 7 contains the conclusions.</p
‘Phenomenology’ is Blue: The Synaesthetic Dynamics of Being-in-the-World
No full textNo description supplie
Development of ambient-cured high-strength fibre-reinforced self-compacting geopolymer concrete
No full textThe abstract for this item has not been populated.</p
WOMBAT v2.S: A Bayesian inversion framework for attributing global CO₂ flux components from multiprocess data
No full textContributions from photosynthesis and other natural components of the carbon
cycle present the largest uncertainties in our understanding of carbon dioxide
(CO) sources and sinks. While the global spatiotemporal distribution of the
net flux (the sum of all contributions) can be inferred from atmospheric CO
concentrations through flux inversion, attributing the net flux to its
individual components remains challenging. The advent of solar-induced
fluorescence (SIF) satellite observations provides an opportunity to isolate
natural components by anchoring gross primary productivity (GPP), the
photosynthetic component of the net flux. Here, we introduce a novel
statistical flux-inversion framework that simultaneously assimilates
observations of SIF and CO concentration, extending WOMBAT v2.0 (WOllongong
Methodology for Bayesian Assimilation of Trace-gases, version 2.0) with a
hierarchical model of spatiotemporal dependence between GPP and SIF processes.
We call the new framework WOMBAT v2.S, and we apply it to SIF and CO data
from NASA's Orbiting Carbon Observatory-2 (OCO-2) satellite and other
instruments to estimate natural fluxes over the globe during a recent six-year
period. In a simulation experiment that matches OCO-2's retrieval
characteristics, the inclusion of SIF improves accuracy and uncertainty
quantification of component flux estimates. Comparing estimates from WOMBAT
v2.S, v2.0, and the independent FLUXCOM initiative, we observe that linking GPP
to SIF has little effect on net flux, as expected, but leads to spatial
redistribution and more realistic seasonal structure in natural flux
components.</p