Towards therapeutic modulation of the epigenome in females with X-linked liver disease using Adeno-Associated Viral vectors

Allele-specific reactivation of healthy gene copies on the inactive X chromosome (Xi) has the potential to restore expression of absent proteins for therapeutic benefit as a method of treating X-linked disorders. Elimination of the master regulator XIST RNA may be required for success, however subsequent chromosome-wide Xi reactivation may lead to dosage imbalance of X-linked genes. Other approaches such as the recruitment of transcriptional activators using CRISPRa at the target loci offers the advantage of targeted effect. Here, we utilised our recently published novel model system, chimeric mouse-human FRG livers produced from hepatocytes derived from a heavily skewed female patient liver explant with the X-linked metabolic liver disorder, OTC deficiency, to investigate the effects of XIST RNA elimination and recruitment of a transcriptional activator in vivo. We observed that deletion of XIST in female patient hepatocytes in vivo, led to reactivation of the healthy OTC gene from the Xi. However, we also observe that elimination of XIST RNA causes potentially abnormal consequences on the epigenome environment of the human X-chromosome. To overcome the challenges and limitations associated with targeting the entire X chromosome, a locus-specific strategy was also explored to target the OTC promoter through the recruitment of a transcriptional activator. This strategy of modulating the epigenome induced expression of OTC in vitro and proved that the locus is amenable to editing, however no transcriptional activation was detected in the patient derived primary human hepatocytes. Additional analysis elucidated challenges inherent in delivering epigenome editing reagents efficiently to primary human cells in an in vivo setting. This thesis lays early foundations for overcoming hurdles associated with translating liver-targeted epigenome editing strategies from bench side to bedside, through bridging the gap between the gene therapy and the epigenome editing fields

Strategic Airline Decarbonisation from a Door-to-Door Perspective

This thesis examines practical, near-term ways for airlines to cut emissions as climate pressures intensify. Aviation produces ~2.5% of global CO₂ (close to 5% of non-CO2 effects are included). With passenger demand continuing to grow, unchecked growth could expose airlines to significant risks. Rather than waiting for future technologies, the research focuses on “low-hanging fruit”: ready-now, cost-effective measures that can be implemented quickly, complementing longer-term solutions such as sustainable aviation fuel (SAF) and hydrogen. Two pillars anchor the thesis. First, airline carbon calculators are gate-to-gate, ignoring ground connections. In car-dependent markets, these ground segments can add up to 22% to total trip emissions. A novel door-to-door (D2D) model shows that simple shifts to airport ground trips can save more CO₂ on busy domestic routes than SAF blends at lower cost. The thesis tests how travellers respond when D2D CO₂ communication during flight booking. Choice experiments with 1,000+ respondents in Australia and New Zealand show meaningful shifts toward greener ground options, especially on shorter routes. Second, choice experiments assess willingness-to-pay (WTP) for SAF via book-and-claim carbon offsets. It reveals most passengers offer premiums far below SAF’s current cost, highlighting financial risk if SAF mandates expand without policy support. A latent-class analysis identifies three segments: enthusiastic supporters (25%), indifferent avoiders (13%), and a cautious majority (62%). Stronger, verifiable traceability (e.g., blockchain-enabled tracking) boosts carbon offset’s uptake especially amongst the last cohort. The thesis recommends embedding D2D calculators in booking flows, using targeted policy to narrow the SAF cost-WTP gap, and redesigning offsets around radical transparency. It extends carbon accounting beyond the airport fence and provides tools airlines and regulators can deploy within quarters, not decades

Acute Effects of Novel Rest Interval Strategies in Resistance Training on Exercise -Related Outcomes Across Young, Older, and Clinical Cohorts

Resistance training (RT) is essential for improving neuromuscular function and functional capacity, yet the optimal manipulation of rest intervals (RI) remains poorly understood across diverse populations. Novel strategies, such as blood flow restriction during rest intervals (BFR-RI) and cluster sets (CS), have recently emerged in the literature. This thesis investigated the acute effects of BFR-RI and CS on various exercise-related outcomes in healthy young adults, older adults, and individuals with Charcot-Marie-Tooth disease (CMT), a population susceptible to fatigue and functional impairment. Chapter 3 examined BFR-RI during high-load squats in trained young adults. BFR-RI produced similar mechanical, perceptual, and physiological responses to conventional RT, with a small but significant reduction in total repetitions, indicating slightly accelerated fatigue. Chapters 4–6 compared CS versus traditional sets (TRAD) during chest press (CP) and leg press (LP). Across populations, CS generally preserved mean concentric velocity (MCV), attenuated MCV loss - particularly in CP - and increased estimated repetitions to failure. Reductions in rating of perceived exertion were only observed in young adults, and lower-functioning CMT participants were more likely to terminate CP sets early. The study in young adults elucidates minimal sex and strength impact on MCV attenuation. Overall, CS improved acute performance and mitigated neuromuscular fatigue, particularly during CP, whereas BFR-RI offered minimal advantage over conventional RT. These findings highlight RI as a key training variable and support CS as a practical strategy to maintain performance and potentially reduce neuromuscular fatigue in healthy and clinical populations. Future research should explore individualized CS protocols, alternative set structures, and long-term adaptations to optimize outcomes, safety, and adherence, especially in populations vulnerable to fatigue or functional limitations

Plastic and organic waste photoreforming for green hydrogen evolution and valuable products

As the world transitions to a carbon-neutral future, photoreforming offers a promising route to address two challenges simultaneously: waste reduction and renewable energy production. In this process, a photocatalyst harnesses sunlight to drive water reduction to hydrogen and waste oxidation to organic compounds under ambient conditions. This thesis investigates ambient-temperature photoreforming of plastic and biomass waste using platinum-loaded graphitic carbon nitride (Pt/g-C3N4 or Pt/CN) for its visible-light response, chemical stability, and availability. Four nitrogen-rich precursors (dicyandiamide, melamine, thiourea, urea) were studied to assess their effect on g-C3N4 properties and PET photoreforming. Melamine-derived g-C3N4 with 3 wt.% Pt achieved the highest hydrogen evolution rate (7.33 mmol H2 gcat-1 h-1) and stable PET conversion to valuable organics over 8 days, attributed to its higher crystallinity and chemical resistance. To further improve performance, post-thermal and chemical oxidation treatments were applied to melamine-derived g-C₃N₄, producing high-surface-area (>400 m2 g-1), hydrophilic photocatalysts. These enabled efficient photoreforming of biomass-derived 5-(hydroxymethyl)furfural (HMF) in neutral water, achieving hydrogen evolution rates nearly four times higher than untreated CN and maintaining stability over five days. The influence of synthesis temperature on CN properties was also explored for real-world plastic waste. Pt/CN550 showed high activity for PET and other plastics, outperforming P25. Its optimal performance arose from balanced crystallinity, surface reactivity, and co-catalyst formation. Overall, this work demonstrates the potential of g-C₃N₄-based catalysts for integrated hydrogen production and sustainable plastic/biomass waste reforming, providing valuable insights for future recycling strategies

NETS NSW Paediatric Trauma Inter-hospital Retrieval: A 10-year review of patient outcomes

In New South Wales (NSW) there are multiple trauma transport providers. With only 3 paediatric trauma centres (PTC), nearly half of paediatric major trauma cases require inter-hospital transfer to reach definitive care. International literature reports reduced hospital length of stay (LOS), reduced mortality and reduced adverse events during transport for paediatric trauma patients retrieved by paediatric specialist teams compared to adult teams and paramedics. This study examined the quality of care delivered to paediatric trauma patients requiring inter-hospital transfer in NSW. This is a retrospective observational study of trauma patients aged 0-15 years, referred to the Newborn and paediatric Emergency Transport Service (NETS NSW) and were medically retrieved or transported to a PTC between 1 January 2010 and 31 December 2019. The primary outcome was acute morbidity, measured by admission to paediatric intensive care unit (PICU), and lengths of stay in PICU and hospital. Nine-hundred and thirty-two patients were included in the final analysis. We found no difference in PICU admission rate; PICU LOS; or hospital LOS between the paediatric retrieval team (NETS NSW) and the adult medical retrieval service (AMRS). There was a higher PICU admission rate for the regional retrieval service in this study, and this was associated with a shorter PICU and hospital LOS. NETS NSW teams on average spent the same amount of time stabilising patients at the referring hospital as AMRS teams. However, this study identified potentially modifiable delays related to teams reaching the patient’s and in NETS NSW teams’ departure once the patient was stabilised. Within the current trauma system, the inter-hospital transport process and providers are delivering an equitable level of service as measured in mortality, morbidity and time-based outcomes. However, opportunities exist to improve upon the medical retrieval response times

Supercritical water - actions and reactions during the thermal decomposition of plastics

Current estimates suggest that there will be more plastic than fish in the oceans by 2050 if the mounting plastic waste problem that society is facing remains unaddressed. New technologies will be required in order to shift society towards a circular economy which will support a more sustainable future. Hydrothermal liquefaction (HTL) shows promise to be a major part of the solution for dealing with the rapidly growing quantities of plastic waste generated each year. Yet, there are still many unknowns pertaining to the reaction pathways occurring during the HTL of plastic wastes. The work within this thesis will explore the role that water plays during the decomposition of plastic waste in sub- and supercritical water. Water’s role as a solvent and a reactant will be investigated and clarified. Chapter 2 focuses on the reactivity of water with a hydrocarbon substrate. Contradictory claims in the literature about whether water or oxygen are responsible for the formation of oxygenated compounds have been clarified. Adventitious oxygen was found to be responsible for formation of oxygenated species, which is consistent with mechanisms proposed for SCWO. Chapter 3 examines the behaviour of scrap tyres in HTL. The particle size of a tyre granulate sample was varied to examine effects on the product distribution. Fundamental reaction pathways responsible for the decomposition of the polyisoprene chain are identified. Chapter 4 is a studies the HTL conversion of limonene to aromatics. The behaviour in supercritical water has been identified to diverge from previously published pyrolysis of limonene and the role of water was identified as promoting isomerisation of the double bonds within limonene. Chapter 5 focuses on the hydrothermal decomposition of polyamides. Whilst the behaviour in subcritical water is well known, the same cannot be said about the behaviour in supercritical water. A hydrolysis mechanism accounts for the observed behaviour at all conditions examined

Teratogenic effects of larval low salinity experience in development of the juvenile body in Acanthaster sp

This item is the dataset and the Rscript supporting the manuscript titled - Teratogenic effects of larval low salinity experience in development of the juvenile body in Acanthaster sp. This dataset captures experimental results investigating the effects of reduced salinity during the larval stage on the morphological development of juvenile crown-of-thorns starfish (Acanthaster sp.). The data reflect teratogenic outcomes such as abnormal body plans, arm number deviations, and survival metrics under different salinity and exposure durations. The Excel file contains five sheets: Juvenile growth Measurements of juvenile body diameter (µm) by larval salinity treatment, exposure duration, and age (1 or 5 days). Includes replicate IDs. Proportion normal Proportions and percentages of juveniles categorized as "normal" or "abnormal" based on morphology, by treatment and exposure time. Proportional arm count Relative frequencies of different arm numbers (e.g., 4, 5 arms) in juveniles across treatments and ages. Arm# Detailed arm count data per individual juvenile, including counts of individuals with 0, 4, or 5 arms and corresponding treatment metadata. Juvenile morphology scores Individual-level scoring of morphological abnormalities (e.g., fleshy body, swelling) by treatment, replicate, and juvenile ID. Key Variables: Larval salinity treatment (‰) Larval salinity exposure duration (e.g., 2 or 4 days) Juvenile age (days post-settlement) Morphological traits (arm number, body diameter, abnormality scores) Proportional outcomes (normal vs. abnormal development) This R Markdown file contains all statistical analyses and data visualizations supporting the manuscript "Teratogenic effects of larval low salinity experience in development of the juvenile body in Acanthaster sp." (Clements et al., 2025). The code enables full reproducibility of the analyses, including data import, summary statistics, linear and generalized linear mixed models, and diagnostic assessments. Contents: Packages used: readxl, dplyr, ggplot2, cowplot, lme4, car, emmeans, DHARMa, lattice, arm Main analyses include: Juvenile growth (1- and 5-day-old) Body and arm morphometrics Normal vs. abnormal morphology scoring Five-arm development likelihood Residual and random effects diagnostics Data linkage: External Excel file (.xlsx) referenced for input data Usage: This file is intended for transparent and reproducible research. Users can rerun all analyses and regenerate figures by updating the file paths to match their system.Adult Acanthaster spp. (crown-of-thorns sea stars) were collected from the Great Barrier Reef and spawned in aquaria at 26–27 °C. Larvae were cultured under controlled conditions and exposed to reduced salinity treatments (22, 25, 30, 34‰) for two or four days to simulate runoff conditions. After exposure, competent larvae were settled in standard salinity using coralline algae as a cue, and resulting juveniles were monitored for five days. Morphometrics (body size, arm number) and morphology scores (normal vs. abnormal) were recorded on days 1 and 5. Statistical analyses included linear and generalized linear mixed models with salinity and exposure time as fixed effects, and replicate vial as a random effect. Model assumptions were validated using diagnostic tools in R

Developing All Abilities Touch Football: Foundations for a Classification Framework

Approximately 16% of the global population is estimated to live with a disability. However, individuals with disabilities are less likely to meet physical activity guidelines compared to their non-disabled counterparts. They are also twice as likely to be physically inactive, which increases their risk of developing chronic health conditions associated with inactivity. All Abilities Touch Football (AATF) offers individuals with intellectual and/or physical impairments an opportunity to participate in organised sport and develop their skills in a supportive environment. However, as AATF’s sporting profile continues to grow, accommodating players with diverse abilities in the same sport while ensuring fair and safe competition is becoming increasingly challenging. This thesis aimed to provide a comprehensive understanding of AATF, offering foundational insights to enhance participation and playing opportunities for AATF players while evaluating the feasibility of implementing a classification framework for the sport. Chapter Two presents a systematic review of impairment and activity limitation measures used in Para sport classification. Chapter Three explores stakeholder perspectives on the current challenges and opportunities in AATF, including the potential for a classification framework. Chapter Four assesses the range of player abilities by measuring physical performance through fitness tests and observing activity limitations. Chapter Five quantifies the demands of AATF competition. The findings emphasise the importance of redefining the sport’s structure by potentially developing a classification framework to better support a range of player abilities, improve competitive balance, and promote broader participation across all levels of the sport

Cape and Torres Health Commissioning Ltd (CaTHC) Project Final Evaluation Report

In May 2024, the Cape and Torres Health Commissioning (CaTHC) Ltd was established as a regional community-controlled commissioning entity. CaTHC is governed by a Board of Aboriginal and Torres Strait Islander Directors and is independent from government. It is planned that over a 10-year period CaTHC will develop the capabilities to receive public funding and commission health services that respond to community need. The aim is to shift the way care is planned, purchased, and delivered, to drive improved health system effectiveness, equity and whole of population health and wellbeing outcomes. This report provides a detailed evaluation of the CaTHC project covering the period of entity establishment between August 2022 and December 2024. It focusses on project deliverables and resourcing; collaboration and governance; model design and implementation; and community and engagement. The project was formerly called the Torres and Cape Health Care Commissioning Fund (TORCH), with a name change to the CaTHC project in 2024

Realising the Value of Digital Tools for Personalised and Measurement-Based Care in Youth Mental Health Services

Mental ill-health among youth is a global concern, affecting one in seven adolescents. Despite rising demand, timely and appropriate care remains limited, partly due to the heterogeneous and comorbid nature of youth symptoms. Blended care models, which integrate digital tools into traditional services, offer scalable solutions for care stratification and personalised measurement-based care (MBC). However, the uptake of these tools in youth mental health services is suboptimal. While engagement moderators have been identified, understanding of the mechanisms driving sustained engagement remain limited. This thesis evaluates capacities and engagement of digital tools for personalised MBC in services. Chapter 2 validates a rule-based algorithm that differentiates young people at lower and higher risk of developing full-threshold mental disorders. Chapter 3 examines a digital suicidality notification system, showing its capacity to trigger timely clinical responses based on acuity. Chapter 4 explores barriers and facilitators of digitally-enabled MBC among youth, while Chapter 5 investigates their experiences of using a digital MBC tool as part of routine care in real-time. Findings of Chapters 4 and 5 reveal their enthusiasm for integrating digital tools into care. However, they also demonstrate clinical relevance and collaborative use with clinicians as critical factors for sustained engagement. Chapter 6 further supports the importance of clinical relevance by demonstrating that personalising the tool use through a goal-setting feature enhances engagement, leading to frequent and prolonged use. Altogether, this thesis highlights the potential of digital tools to deliver timely and personalised care. Furthermore, by introducing the Realisation Chasm, the gap between young people’s expectations for digital MBC tools and the realisation of their benefits, this thesis provides strategies for ensuring meaningful integration of digital tools into mental health services