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Development of Novel Dose Quantification Methods for Heavy Ion Radiotherapy Using In-Beam Positron Emission Tomography Imaging
Ion therapy is a radiotherapy technique that employs accelerated ions, such as helium or carbon, to deliver a therapeutic dose to a target volume. This method delivers a highly conformal dose distribution, resulting in steep dose gradients surrounding the treated area. Consequently, minor errors in treatment delivery can lead to substantial discrepancies in dose delivered both to the target volume and healthy tissue.During helium and carbon ion therapy, some ions in the beam undergo nuclear inelastic collisions with atoms along the beam path, generating various fragment particles, including positron-emitting radioisotopes. Images of the distribution of positron-emitting fragments can be acquired using positron-emission tomography, which can be compared to a predicted distribution to verify the treatment location. However, a more clinically relevant and valuable measurement of treatment quality is the quantitative estimation of the deposited dose. Calculating the deposited dose using distributions of positron-emitting fragments obtained during and immediately after helium or carbon ion therapy is challenging due to the non-linear relationship between the two quantities.This Thesis evaluates and compares two methods for dose quantification in heavy ion therapy using the distribution of positron-emitting fragments. First, an iterative dose estimation procedure is developed for carbon ion therapy and evaluated using both Monte Carlo simulations and experimental irradiations in a homogeneous medium. This method is then extended to experimental helium ion irradiations to assess the model’s performance for the case where positron-emitting fragments are created only through target fragmentation. A complementary study examines the impact of heterogeneities in the treated volume. Subsequently, a deep learning approach, based on an InceptionTime-InceptionResNet hybrid model is then designed and implemented for simulated and experimental carbon ion treatments. The two dose quantification approaches are compared and contrasted based on accuracy and speed.</p
Studying the interactions between aggregation-prone proteins and molecular chaperones using single-molecule fluorescence-based techniques
There are a number of cellular mechanisms that act to maintain the folded and functional state of the proteome, including the highly conserved molecular chaperone proteins. Molecular chaperones act to prevent protein aggregation and comprise a diverse range of sub-classes; these include the small heat shock proteins (sHsps), which function independently of ATP, and the Hsp70 system which are ATP-dependent. Molecular chaperones are inherently heterogeneous and dynamic proteins, and protein aggregation itself is also extremely heterogeneous. Single-molecule techniques have emerged as a powerful tool to study chaperone function and the interaction of chaperones with their client proteins; this is largely owing to their capacity to visualise rare or dynamic features in individual proteins that are typically masked in ensemble-averaging techniques. The work in this thesis aimed to utilise fluorescence-based single-molecule techniques, in particular total internal reflection fluorescence (TIRF) microscopy, to observe and quantify the interactions between molecular chaperones and their clients.This work first involved the development of an analysis workflow to calculate the number of subunits per protein oligomer from single-molecule photobleaching trajectories. Previous methods to calculate subunits within protein assemblies via single-molecule photobleaching were typically comprised of highly manual and subjective elements. In this work a generalizable machine-learning tool, called py4bleaching, was developed and optimised to identify photobleaching trajectories which are appropriate for further analysis. This machine-learning tool was integrated into an automated analysis workflow which can be easily implemented to analyse data output from a range of experimental designs. Py4bleaching was subsequently used throughout this work to quantify the number of protein subunits from single-molecule data.</p
The Role of Continuum Conceptualisations of Mental Illness on Adolescent Mental Health Stigma and Intentions to Seek and Provide Help
The promotion of adolescent mental health has been identified as a global health priority. Despite the significant negative impacts of mental illness, many young people do not seek help. Stigma has been identified as one of the key barriers to help-seeking among adolescents and remains a widespread experience for individuals experiencing mental health difficulties. There has been growing interest in determining whether continuum conceptualisations of mental illness may be capable of combatting stigma among adults. It has been proposed that continuum conceptualisations of mental illness may decrease stigma by dissolving ‘us’ vs. ‘them’ distinctions which are considered a component of the stigma generation process. Recent findings among adults suggest that continuum conceptualisations of mental illness show promise in reducing stigma. However, there has been minimal research on the link between continuum beliefs and adolescents’ stigmatising attitudes towards both other adolescents and people in general who have mental health difficulties. Likewise, there is a lack of research into the potential relationships between continuum beliefs and important outcomes of mental health promotion such as intentions to seek and provide help. The purpose of this thesis is to examine the links between continuum beliefs and stigma, help-seeking and help-providing intentions in adolescents.Study 1 involved a systematic review of 92 Australian mental health webpages to determine how mental health, mental illness, depression, and schizophrenia were conceptualised. Across all webpage foci, there was a greater prevalence of webpages implying continuum rather than categorical conceptualisations. Yet only a minority of webpages explicitly presented continuum conceptualisations. Webpages for both depression and schizophrenia implied many mixed conceptualisations including both continuum and categorical messaging. Finally, all webpages targeting young people included continuum messaging.Study 2 investigated the links between continuum and categorical beliefs, stigma, and intentions to seek and provide help after participants had reviewed vignettes of depression and schizophrenia. One hundred and ninety-three adolescents aged between 13 and 18 years participated. For the depression vignette, continuum beliefs were not related to stigma, help-seeking or help-providing intentions. Conversely, categorical beliefs about depression positively predicted social distance, dangerousness stereotyping, avoidance, and fear. Continuum beliefs regarding the schizophrenia vignette negatively predicted prognostic pessimism, social distance, and stigmatising attitudes, whereas categorical beliefs were positively associated with these variables. Interestingly, continuum beliefs predicted greater intentions to not seek help for schizophrenia.Study 3 extended on prior findings by investigating the relationships between continuum beliefs about mental illness as a general construct, stigma, and intentions to seek and provide help . Mediation analyses allowed the exploration of indirect paths between continuum beliefs and help-seeking and help-providing intentions via stigma. Participants were 591 adolescent males. Continuum beliefs were found to indirectly predict intentions to seek help via decreased social distance, albeit with effects of very small magnitude. There was also a direct negative association between continuum beliefs and intentions to not seek help. Lastly, continuum beliefs predicted intentions to provide help both directly and indirectly via social distance.Study 4 aimed to clarify some of these inconsistent findings through a novel experimental manipulation of continuum and categorical beliefs about schizophrenia in a convenience sample of 271 adults. Two of seven stigma variables were reduced in the continuum belief condition, specifically prognostic pessimism and dangerousness/unpredictability stereotypes. Prognostic pessimism increased in the categorical condition. Help-seeking intentions increased across conditions and there was no change to help-providing intentions. There was no difference between conditions on a novel measure of prosocial behaviour.Overall, these studies show that among adolescents the relationships between continuum beliefs and stigma, help-seeking and help-providing intentions can vary across different types of mental illnesses. Continuum beliefs inversely predicted stigma variables for schizophrenia and general mental illness but not depression. Categorical beliefs consistently predicted greater stigma across both schizophrenia and depression. The findings also suggest that there is a very weak relationship between continuum beliefs and intentions to seek and provide help. These findings provide some support for the use of continuum as opposed to categorical conceptualisations within adolescent mental health promotion. However, there is not sufficient evidence to suggest continuum beliefs should be a primary target to improve help-seeking or help-providing outcomes in either adults or adolescents.</p
From stress to support: an ethnographic journey of a staff-led wellbeing intervention in maternity services
Background: Addressing occupational distress in maternal services is imperative to ensuring staff retention and patient safety. Interventions to promote wellbeing among healthcare staff are urgently needed. However, little is known about the implementation of such interventions in hospital maternity services. This study aimed to explore the workplace demands and stressors experienced by healthcare staff in hospital maternity services and identify how these demands and stressors affect engagement in workplace wellbeing activities. Methods: This qualitative study employed an ethnographic approach in maternity services in regional Australia. Data were collected through observations over a 12-week period before and during the implementation of a wellbeing program called SEED. Participants included healthcare staff and leaders employed in maternity services. Key themes and insights from the observational data were identified through reflexive thematic analysis. The study followed COREQ guidelines to report key aspects of the research team, methods, context, findings, and analysis. Results: Six themes were identified, depicting both the challenges and opportunities for implementing workplace wellbeing activities in maternity services. The first three themes highlighted pre-existing challenges that affected staff engagement in wellbeing activities: (1) Disconnection Across the Service; (2) Balancing Role Expectations and Wellbeing at Work; and (3) Leaders Trusting in Wellbeing but Staff not Trusting in Leaders. The subsequent three themes described opportunities for engagement: (4) Staff are the Experts of Their Own Wellbeing and Work Environment; (5) Fostering Connection through Conversations; and (6) Cultivating Camaraderie within the Service. Conclusion: By identifying challenges such as disconnection and lack of trust, alongside opportunities like collaboration and camaraderie, the findings provide actionable insights for designing effective wellbeing activities. Gaining leaders’ trust and commitment, followed by engaging staff in collaborative decision-making, is crucial for successful implementation. This research contributes to the global clinical community by providing a nuanced understanding of workplace wellbeing implementation in maternity services, offering a blueprint for similar interventions in healthcare settings worldwide.</p
Investigating the effects of recursion in convolutional layers using analytical methods
Most Convolutional Neural Networks (CNNs) consist of a number of stages of decreasing spatial resolution and increasing channel dimension between succeeding stages, each stage is composed of convolutional blocks that are repeated a number of times. Previous research on very simple CNNs consisting of a number of convolutional layers in each stage demonstrated that the introduction of feedback loops around convolutional layers can improve results. This paper studies the effectiveness of recursion on convolutional blocks in a more general setting and aims at explaining the results. Four recent models, namely ResNet, Inception, MobileNet and DenseNet are considered in this study. It is found that for all but DenseNet, the recursive version produces results that are similar or better than their feedforward counterpart when the number of convolutional blocks are preserved. To understand this finding and to discriminate the functional behaviors of the feedforward and recursive counterparts, we embark on three investigations: (1) measuring the evolution of the contextualization of the neurons of the last layer using the effective receptive field concept; (2) comparing the position and the size of the global coverage of the networks using class activation maps; and (3) analyzing the evolution of the organization of the feature space prior to the classifier using the Silhouette score. The investigations reveal that the recursion of a convolutional block shares many similarities with the behavior of a sequence of that block, indicating that a recursive alternative consisting of a single physical layer, can be regarded as a “faithful simulation” of its deeper‘feedforward counterpart. We conclude that except for densely connected models, the recursion of convolutional blocks is a safe and powerful alternative enhancing modern network architectures.</p
Behaviour, Social Structure and Population Genetics of the Burrowing Shrimp, <i>Trypaea australiensis</i>
Burrowing shrimp, such as Trypaea australiensis (Decapoda, Axiidea, Callianassidae), play vital ecological roles as ecosystem engineers by modifying sediment structure and water quality through their burrowing activities. These alterations affect a wide range of organisms, from microorganisms to larger fauna and flora. Despite their ecological importance and widespread use as bait in recreational and commercial fisheries, their behaviour, social systems, and population dynamics remain poorly understood due to their cryptic lifestyles. This knowledge gap not only raises concerns about potential overexploitation but also hinders the development of effective conservation and management strategies. This thesis investigates the social structure, burrowing behaviour, and population genetics of T. australiensis. Our findings from field surveys revealed diverse social structures, with individuals primarily solitary but also forming pairs (including same-sex and opposite-sex pairs) and sometimes groups, with social structure being influenced by body size, seasonality, and location. To further exploration social behaviours and enable comparisons with field data, we conducted manipulative experiments at the Ecological Research Centre (ERC) at the University of Wollongong, where conspecifics of both sexes were introduced into the burrow of a resident shrimp. These laboratory manipulations revealing greater tolerance for opposite-sex individuals, albeit temporarily. In another laboratory experiment, we explored the likely mechanism by which shrimp formed pairings by allowing 2 shrimp to simultaneously burrow within the same aquaria. These shrimp were found to connect their burrows when in proximity to a neighbouring shrimp and more frequently did so when they were of opposite sex. Additionally, burrow structure was assessed using field-collected resin casts, 3D scanning and laboratory behavioural observations of solitary shrimp. Burrow morphology through resin casts indicated variations in depth and complexity between sites, while laboratory observations showed that shrimp dedicate significant time to burrow maintenance. Finally, genetic analysis using SNP markers across three locations indicated no significant population structure, suggesting high gene flow and providing crucial preliminary population genetic data for T. australiensis that supports management of T. australiensis as a single unit. All in all, this thesis provides new insights into the social and burrowing behaviours of a key cryptic species. The results underscore the ecological significance of burrow habitats and highlight the need for further research on cryptic invertebrates to guide effective conservation and fisheries management.</p
Studying the Biomechanics of Steel Construction Activities Using Musculoskeletal Modelling and Wearable Sensors
In Australia, the construction industry contributed around 10% GDP and comprised 12.2% of all work-related physical harm and health problems in 2021-2022, ranking second among all industries. Helping construction workers to mitigate work-related musculoskeletal disorders (WMSDs) not only benefits the individuals involved but also society, fostering a win-win scenario. One possible solution to achieve this goal is the utilization of sensors to monitor the movements and loads on workers during construction activities, assessing their safety. Research in this area has applied wearable sensors including inertial measurement units and smart insoles to identify high-risk activities by collecting data on kinematics and external loads to compute biomechanical loads. However, wearing full-body sensors can cause discomfort, and utilizing optical motion capture systems is often not practical in worksite conditions. In this thesis, conventional laboratory-based motion capture technology was used in conjunction with a custom-built wearable sensor suit (WSS) with just three IMUs and a pair of smart insoles to record the kinematics and external forces of the participants during activities typical in the steel construction industry. The purpose of this study is to 1) quantifying biomechanical parameters including cumulative low-back load, muscle activation, joint moment, joint reaction force, muscle force, and muscle metabolic cost in panel lifting and drilling tasks. 2) Explore the relationship between the construction activities and data collected from WSS. The laboratory motion capture data, a whole body musculoskeletal model and the software OpenSim form the basis for estimating joint moments, muscle forces, and joint reaction forces (JRFs) during the activities. The analysis of the musculoskeletal results revealed that compared to lifting from ankle height, lifting a shear panel from thigh height and chest height resulted in a decrease in cumulative low-back load (CLBL) by 49.3-71.9% and 76.3%-89.8%, respectively. Additionally, for drilling, compared to plates with 2mm thick pre-drilled holes, drilling on plates without pre-drilled holes required an additional 59% to 269% of Triceps power consumption; drilling on plates with 4mm pre-drilled holes required an additional 8% to 154% of Triceps power consumption. Initial relationships were built between these “ground-truth” results and the WSS data, to shed light on how effectively the WSS could independently predict high loading conditions. These findings provide essential insights into biomechanical loads during steel construction tasks and highlight the potential of the WSS for real-time, non-laboratory monitoring to reduce WMSDs across the steel construction tasks.</p
Curve shortening flow with an ambient force field
In this paper we consider the anisotropic curve shortening flow in the plane in the presence of an ambient force. We consider force fields in which all their derivatives are bounded in the L∞ sense. We prove that closed embedded curves that have a minimum of curvature sufficiently large shrink to round points. The method of proof follows along the same lines of Gage and Hamilton, in that we study a rescaling to prove curvature bounds. We additionally show that the influence of an ambient force field may make such a result untrue, by giving sufficient conditions on the ambient field that ensures eventual non-convexity of an initially convex curve evolving under the flow.</p
Environmental engagement, business operation and corporate policies
Climate change presents a significant challenge to business operations, introducing both physical risk and transition risk. To mitigate these risks and achieve environmental goals, corporations engage in environmental activities designed to protect environment and cater to stakeholders. However, the impacts of such environmental investments on business risks and market values remain controversial, forming the core theme of this thesis. To address these issues, this thesis explores three key aspects organized as follows.Chapter 2 focuses on the impact of environmental engagement on lawsuits related to environmental violations. The purpose of this chapter is to explore the impact of socially responsible behaviours on business litigation risks, and specifically, whether engagement in environmental activities can effectively reduce exposure to environmental litigation risks. The empirical analysis shows that environmental engagement can reduce the likelihood of environmental lawsuits, and this effect is robust when considering the potential endogeneity issues. Further analysis shows that improved environmental performance is the key channel through which environmental engagement reduces environmental lawsuits. The heterogeneity analysis indicates that the negative impact of environmental engagement on environmental lawsuit risk is more significant for non-SOEs, firms from high-pollution industries, firms located in high-pollution provinces and low trust provinces. These results clearly demonstrate that environmental engagement can satisfy the stakeholders’ requirement for social responsibility, and thereby leads to low litigation risks.Chapter 3 examines the effect of environmental engagement on financial risks, reflected by the bank loan access. The results show that banks are likely to extend credits to firms that invest more in environmental protection activities, although this effect is observed only for short-term loans. The primary reason is attributed to the agency problem, where bank managers, concerned about the bank performance, prefer to grant short-term loans that allow them to closely monitor the borrowers’ financial risks. The channel analysis reveals that improved social trust and reduced financial risks are two key mechanisms through which environmental investment can lead to more bank loans. Further analysis shows that the impact of environmental investment on bank loan access is stronger for non-SOEs and firms with lower ESG rating. This chapter highlights the necessity of establishing a theoretical framework combining stakeholder theory and agency theory to develop more in-depth predictions, aiming to understand how and when environmental engagement can have a meaningful impact.Chapter 4 investigates the impact of environmental investment on market values, by examining the announcements of accounting frauds. Extant literature has shown that alleged frauds result in large loss of market value, due to the disruption of investor confidence and trust. This chapter thus aims to explore whether environmental engagement can restore market reputation and rectify the biased business strategy. Empirical results show that firms increase their environmental engagement following the announcements of frauds, and these environmental engagement activities are effective in improving the stock returns. However, such efforts do not meaningfully alter the opinions of informed market participants, including institutional investors, analysts and auditors. While firms could choose to improve the internal corporate governance to restore the market value, this is not observed in Chinese capital market. This chapter highlights the information asymmetry between informed investors and public investors who are lack of inside information, which leads to biased investment decisions.</p
Norms-Driven Behaviour Change for GHG Reduction: A Meta-Analytic Review of High and Low Involvement Behaviors
This meta-analysis explores how Normative Conduct Theory explains high-involvement behaviours, such as choosing electric vehicles, and low-involvement behaviours, such as reducing meat intake – both aimed at lowering carbon emissions. The study reveals that personal norms, descriptive norms, injunctive norms and social norms positively correlate with both behavioural categories examined. Personal norms are found to have the most significant impact on low-involvement behaviours, aligning with existing literature. In contrast, injunctive norms are the most influential for high-involvement behaviours, such as selecting electric vehicles, suggesting that these choices are strongly impacted by recommendations from significant others. Descriptive norms, social norms and personal norms follow in their influence on EV uptake. The analysis highlights the complex role of normative influences in promoting carbon reduction behaviours, providing valuable insights for advancing theoretical understanding and developing practical interventions to encourage sustainable choices.</p