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BCyrius: An Upgraded Version of Cyrius for Accurate CYP2D6 Genotyping From Short-Read Sequencing Data
No full textPharmacogenomics is a field of personalized medicine that aims to tailor drug dosing based on the genetics of an individual. The polymorphic and complex CYP2D6 gene is important to analyze because of its role in the metabolism of approximately a quarter of all drugs. Several bioinformatic tools have been developed to genotype CYP2D6 from short-read sequencing data. Among these, Cyrius, a tool specifically designed for CYP2D6 genotyping, has demonstrated high performance across various datasets. However, Cyrius has not been updated in the past 3 years, during which dozens of new star alleles have been identified and some previously defined ones revised. In this work, we simulated all known CYP2D6 haplotypes to assess the ability of Cyrius to identify them. In that dataset, Cyrius was unable to call or misidentified 50 of 360 samples. Given the importance of providing an up-to-date tool, particularly in clinical settings, we present an upgraded version of the tool, named BCyrius, which includes all the missing star alleles as well as revisions to the previously listed ones. BCyrius successfully identified 100% of the currently defined minor star alleles, higher than Cyrius (85.6%) and the two other tested tools, Aldy and StellarPGx, which identified 92.2% and 87.8%, respectively. BCyrius also demonstrated slightly improved performance on a dataset of real biological samples, resulting in a higher call rate while maintaining similar accuracy with Cyrius. In addition to providing genotyping results, BCyrius also reports the predicted phenotype, along with information for each detected haplotype, including population frequencies
Folio of Compositions
No full text© 2025 James HutchinsonThis folio of five original works marks a compositional journey of reflection and renewal, capturing shifts in musical language and in how I listen and respond to sound, nature, and narrative. The research component explores composition as inquiry into ecological soundscape as creative practice.
Awakening, an orchestral work, develops from restrained beginnings into a broader sonic landscape. It takes the listener on a dawn walk through an awakening forest to an expansive vista, exploring emergence, layered textures, and atmosphere shaped by orchestral colour.
Bats, a three-movement eco-acoustic work, combines field recordings, vocal textures, and electronic sound design to evoke the world of grey-headed flying foxes. Its movements trace dusk roosting in Yarra Bend woodlands, nocturnal feeding across the city skyline, and the return over Melbourne, encountering urban sounds such as nightclubs and trams. The work highlights eco-acoustic practice in the sonic reimagining of landscape.
Prelude 54, loosely based on Bach’s Prelude No. 1 in C Major, develops rhythmic tension, tonal clustering, and metric variation. Its companion work, Serein, conveys imagery and emotion through motivic development.
Dysco Dystopia explores genre synthesis and electronic idioms, referencing disco cliches, dystopian textures, cultural samples, and an electronic fugue, before concluding with a playful squeaky pop.
Across these works, the folio demonstrates research through creative practice, examining eco-acoustic environments, deconstruction of tradition, and genre hybridity, while revealing a broad palette of influences and bold harmonic and stylistic choices
The prevalence of intimate partner violence in Australia: a national survey
No full textOBJECTIVES: To estimate the prevalence in Australia of intimate partner violence, each intimate partner violence type, and multitype intimate partner violence, overall and by gender, age group, and sexual orientation. STUDY DESIGN: National survey; Composite Abuse Scale (Revised)-Short Form administered in mobile telephone interviews, as a component of the Australian Child Maltreatment Study. SETTING: Australia, 9 April - 11 October 2021. PARTICIPANTS: 8503 people aged 16 years or older: 3500 aged 16-24 years and about 1000 each aged 25-34, 35-44, 45-54, 55-64, or 65 years or older. MAIN OUTCOME MEASURES: Proportions of participants who had ever been in an intimate partner relationship since the age of 16 years (overall, and by gender, age group, and sexual orientation) who reported ever experiencing intimate partner physical, sexual, or psychological violence. RESULTS: Survey data were available for 8503 eligible participants (14% of eligible persons contacted), of whom 7022 had been in intimate relationships. The prevalence of experiencing any intimate partner violence was 44.8% (95% confidence interval [CI], 43.3-46.2%); physical violence was reported by 29.1% (95% CI, 27.7-30.4%) of participants, sexual violence by 11.7% (95% CI, 10.8-12.7%), and psychological violence by 41.2% (95% CI, 39.8-42.6%). The prevalence of experiencing intimate partner violence was significantly higher among women (48.4%; 95% CI, 46.3-50.4%) than men (40.4%; 95% CI, 38.3-42.5%); the prevalence of physical, sexual, and psychological violence were also higher for women. The proportion of participants of diverse genders who reported experiencing intimate partner violence was high (62 of 88 participants; 69%; 95% CI, 55-83%). The proportion of non-heterosexual participants who reported experiencing intimate partner violence (70.2%; 95% CI, 65.7-74.7%) was larger than for those of heterosexual orientation (43.1%; 95% CI, 41.6-44.6%). More women (33.7%; 95% CI, 31.7-35.6%) than men (22.7%; 95% CI, 20.9-24.5%) reported multitype intimate partner violence. Larger proportions of participants aged 25-44 years (51.4%; 95% CI, 48.9-53.9%) or 16-24 years (48.4%, 95% CI, 46.1-50.6%) reported experiencing intimate partner violence than of participants aged 45 years or older (39.9%; 95% CI, 37.9-41.9%). CONCLUSIONS: Intimate partner violence is widespread in Australia. Women are significantly more likely than men to experience any intimate partner violence, each type of violence, and multitype intimate partner violence. A comprehensive national prevention policy is needed, and clinicians should be helped with recognising and responding to intimate partner violence
Emerging burden of post-cancer therapy complications on unplanned hospitalisation and costs among Australian cancer patients: a retrospective cohort study over 14 years
No full textCancer treatment using systemic therapy and radiotherapy may cause post-therapy complications, resulting in increased unplanned hospitalisation. The evidence on such complications, their impact on unplanned hospitalisations, and associated costs is scant in Australia. We aimed to estimate the prevalence of post-therapy complications, evaluate their impact on unplanned hospitalisation, length of stay (LOS) and investigate the associated medical costs. A retrospective cohort study was conducted among 8,633 cancer patients (1.03 million emergency hospital admissions) in Victoria, Australia from July 2006 to June 2020, from the Australian healthcare system perspective. Multivariate generalised linear regression models were employed to estimate the adjusted association between post-therapy complications and clinical characteristics with hospital LOS and associated hospitalisation medical costs. Approximately 52% of patients were male with an average patient age of 59.9 years. Annually, post-therapy complications leading to unplanned hospitalisations increased by 7.25%, outpacing the growth in overall hospitalisation admissions, which was 5.66% for overall hospitalisation admissions. A significant proportion of patients (71%) experienced multiple complications, with the most common being anemia (26%), sepsis (15%), nausea and vomiting (14%), and neutropenia (11%). Patients undergoing combined systemic and radiotherapy exhibited higher odds of post-therapy complications (OR = 8.24, 95%CI: 7.48 to 9.08) compared with those who only received systemic therapy. Mean hospital stay among patients who experienced post-therapy complications was 2.23 days per admission (360 days per patient), an extra 1.72 days per admission [95%CI: 1.68 to 1.76; 354 days per patient, 95%CI: 336 to 371 days] longer than patients without complications (0.51 days per admission and 6.48 days per patients). Overall, per-admission medical hospitalisation costs among patients with post-therapy complications were 11,418 vs. 8,685 to 1.82 million higher among patients than those without complications (33,599 per patient, 95%CI: 1.94 million). The cost and hospitalisation stay (in days) varied by the type of therapy and cancer type. The study results indicate that post-therapy complications in cancer patients varied by the type of cancer and increased over the study period, leading to longer unplanned hospital stays and higher hospitalisation medical costs. The results highlight the need for better-customized treatment delivery strategies to address this burden and optimise resources in cancer care
Identifying and Preventing Implementation Flaws in Systems for Privacy and Robustness
No full text© 2025 Jiankai JINDifferential privacy (DP) guarantees that the outputs of machine learning models or data analyses are perturbed in a controlled manner to bound the privacy leakage about any individual participant. Certified robustness (CR) guarantees that a model’s classification remains stable under bounded input perturbations. Together, these frameworks can be applied to facilitate the development of trustworthy AI. Despite the high-profile deployments of these technologies, their system security has received limited attention. To bridge this gap, this thesis presents novel attacks that invalidate their guarantees and proposes corresponding mitigations.
Our first set of contributions builds upon Mironov’s floating-point attack on the Laplace mechanism. We extend this research and demonstrate similar floating-point attacks on the more widely used Gaussian mechanism. These floating-point attacks underscore the necessity of discrete DP mechanisms. However, we identify a timing side channel in the implementations of those mechanisms, enabling attackers to infer the noise magnitude based on program runtime, thereby revealing the true results. To mitigate these attacks, we suggest discarding one of every two sampled noise values to disrupt floating-point attacks and using constant-time discrete noise samplers to eliminate the timing side channel.
Our second set of contributions focuses on the secure deployment of the global DP model in an untrusted environment. While the global DP model offers better utility compared to the local DP model, its adoption is limited due to the high level of trust required in the data curator. To address this, we propose ElephantDP, a secure global DP system that leverages Trusted Execution Environments to establish trust and a State Continuity Module to faithfully track the privacy budget. We implement ElephantDP and observe 1-3x overheads compared to an insecure implementation.
Finally, we shift our focus from privacy to robustness, marking our last set of contributions toward the deployment of trustworthy AI. Due to the floating-point representation problem, the computed robustness certificates can suffer significant rounding in practice, potentially invalidating their intended sound robustness guarantees. We design an attack that exploits this vulnerability and demonstrate its effectiveness against both linear classifiers and neural networks. Finally, we propose a mitigation based on rounded interval arithmetic to account for rounding errors in the computation of robustness certificates
Diversity and plant growth promotion potential of native Australian seed microbiomes for improving restoration outcomes
No full text© 2025 Allison Anne MertinDeforestation is increasing globally, with rates of clearing within Australia rapidly increasing. Once cleared, land becomes degraded and requires restoration, often necessitating revegetation. However, many seeds used in restoration fail to germinate and establish, with some projects having as little as 10% of seeds reaching the seedling stage. Novel strategies to improve rates of seed germination and establishment are required. Seeds contain a microbial community, with studies in agricultural plant species identifying the important role of the seed microbiome in improving plant growth. Although, there is little understanding of what microbes are in seeds of native plants. This lack of knowledge of the diversity, composition and plant growth promoting potential of seed microbes in native plants, reduces their ability to be utilised to improve plant growth in restoration projects. The overall objective of this thesis was to investigate the diversity, composition and plant growth promotion potential of seed microbes in native Australian plants. This thesis used a range of metabarcoding, culturing, microscopy and growth chamber experiments and (1.) improved the accuracy of diversity estimates for seed microbiomes through comparisons of DNA extraction kits, homogenisation methods and peptide nucleic acid clamps, (2.) identified a diverse seed microbiome in native seed, with a set of core species shared between the two grasses, with host species specific responses for retention of this community in restored sites, (3.) cultured and identified the plant growth promotion traits of seed microbes from eight sites and highlighted that soil properties at a site drive the abundance of particular traits, with seeds acting as a ‘microbial reservoir’ of beneficial traits (4.) identified an altered seed microbiome in commercial seed used in restoration, where re-addition of missing microbes, in some instances improved plant growth. The findings of this thesis provide novel insights into the role of seed microbes in plant growth for native Australian plants and identified a hidden diversity of microbes within native Australian seed. This thesis has provided important new knowledge that will help improve restoration of microbial diversity at degraded sites
Adherence and efficacy outcomes in young Australians with suicidal ideation using a self-management app and digital engagement strategy compared with a sham app: a three-arm randomised controlled trial
No full textBackground: Digital interventions are important treatment solutions for suicidal ideation, but premature disengagement is a significant threat to their effectiveness. We tested the adherence to, and efficacy of, two versions of an app-based intervention (app only, app + engagement strategy) for suicidal ideation, compared to a sham app. Methods: This was an online double-blind, three-arm parallel randomised controlled trial in Australia. Recruitment occurred between May 30 and August 8, 2023 and eligible participants were aged 17–24 years and had suicidal ideation in the prior 30 days. They were randomly assigned 1:1:1 to receive (i) LifeBuoy-an app which delivered third wave cognitive behavioural therapy (CBT) skills, (ii) the LifeBuoy app plus a digital engagement strategy, or (iii) a sham app to minimise expectancy bias. The primary efficacy outcome was change in suicidal ideation scores, measured by the Suicidal Ideation Attributes Scale (SIDAS), at 30–, 60– and 120– days post-baseline. The primary engagement outcome was the number of app modules completed at 60–days post-baseline. The final assessment occurred on December 6, 2023. All data was analysed using intention-to-treat. This trial was registered at anzctr.org.au, trial number: ACTRN12621001247864. Findings: 692 participants were assigned (mean age: 19.9 [SD 2.5]; 70% female; intervention (combined): n–459, control: n–233). Significant reductions in ideation scores were observed in the combined intervention condition at 60– (d 0.48) and 120– (d 0.29) days after random assignment compared to the control condition. There were no differences in the number of modules completed between the intervention conditions (OR 1.10, 1.03, respectively) and no significant differences in their ideation scores at any time (ds −0.15 to 0.08). Serious adverse events (hospital presenting non-suicidal self-harm and/or suicide attempts) were reported by 6% of participants during the trial (control condition: 9%; combined intervention condition: 4%). No deaths were reported. Interpretation: A third wave CBT app helped to reduce ideation severity, however providing additional online resources to promote therapeutic engagement did not enhance these effects. Funding: This trial and MT was funded by the National Health & Medical Research Council, Matana Foundation for Young People, Alex Roth Foundation
Electrochemical ammonia synthesis from water and air
No full text© 2025 Amirhamzeh AslambakhshGreen ammonia will be a vital carbon free fuel in the near future to address the transition away from fossil fuels and play a crucial role in agricultural productivity to ease the food shortage and the depletion of natural resources. Nitrogen electrofixation under ambient conditions is a promising approach to synthesize green ammonia sustainably but improving the ammonia yield and process efficiency remains a challenge. This is due to the competition between nitrogen electrofixation and other reactions, such as the hydrogen evolution reaction. The selectivity challenge becomes more important when humified air is used as nitrogen and hydrogen sources to bypass N2 and H2 production. This thesis investigated strategies towards enhancing green ammonia selectivity and yield through catalyst-binder configuration, humidified air and nitrogen, for the purpose of mitigating side reactions, increasing nitrogen concentration and reactivity on the catalyst(s) surfaces and reducing water competition.
To develop novel catalyst-binder configurations, a series of working electrodes were investigated in an aqueous system. Three different binders (Nafion, polyaniline and poly vinylidene fluoride) were investigated, each exhibiting varying levels of electron and proton conductivity, nitrogen affinity and hydrophobicity, with the Faradic efficiency (FE) and ammonia yield of the systems evaluated accordingly. Ruthenium and iron oxide (Fe2O3) were selected as standard catalysts considering their differing electron conductivity and extensively studied for nitrogen reduction reaction (NRR). A cost-effective mesoporous vandanium carbide (V8C7) catalyst was also used fabricated through pyrolysis. The influence of the catalyst-binder configuration was evaluated on ammonia yield and FE, with the proton and electron transfer on the working electrode (WE) found to be dependent on the catalyst material, binder material, and importantly binder hydrophobicity. The use of a binder with low proton/electron conductivity increased FE by hindering the HER and reducing charge transfer to the catalytic material. Utilising a hydrophobic binder also significantly improved ammonia yield, due to reduced water contact with the WE, enabling increased nitrogen sorption. This was demonstrated in sorption experiments that reveal the catalysts’ nitrogen affinity exerted a greater influence on ammonia yield than the binders’ nitrogen affinity.
To address the challenge of generating ammonia from humidified air, a gas-through cell assembly for electrochemical nitrogen reduction reaction (eNRR) was developed in this investigation. The assembly introduced superacidic microdroplets with the nitrogen gas feed, this enhanced nitrogen concentration on the catalyst(s) surface and amplifying nitrogen electrofixation rates. Catalyst deposition on the gas diffusion layer (GDL) surface with a hydrophobic polymer binder enabled microdroplet delivery to the WE surface through an ultrasonic nebuliser. The investigation of such as flow rate, water microdroplet content, temperature, pH, and applied potential provided valuable insights into eNRR performance. Unlike conventional H-cell setups, proton concentration of the nebuliser flow emerged as the primary limiting factor in the gas-through cell assembly, impacting ammonia yield rate and restricted FE. Superacidic droplets enhance ammonia production, but further reducing pH increased hydrogen generation, lowering FE towards ammonia. Higher temperatures accelerate ammonia production but reduce FE due to increased competition from the HER, while elevated potentials boosted eNRR but drop selectivity due to competing reactions.
This investigated extended the process to applying pulsed potential electrochemical nitrogen reduction (P-eNRR) to humidified air to overcome the selectivity limitation and restrict the competing HER. The off-pulse phase ensured time for nitrogen diffusion to the catalyst, enabling the replenishment of active sites and reducing charge consumption. The pulsation process was optimised for the electrocatalyst properties based on two electrode systems, Ru/Nafion and V8C7/ Polyaniline (PANI). The optimal pulsation conditions boasted ammonia formation rate (AFR) and Faradaic efficiency (FE), achieving a threefold increase in both of these parameters for the Ru/Nafion system and a doubling for the V8C7/PANI system. Optimum pulse widths of 250 ms for Ru/Nafion and 750 ms for V8C7/PANI were determined, with the Ru/Nafion system benefiting from shorter pulses to facilitate effective nitrogen diffusion. Notably, the optimal applied potential remained consistent between non-pulsed and pulsed operations.
In conclusion, this thesis demonstrated the ability to generate green ammonia from humidified nitrogen and air at competitive yields and FE, through novel catalyst-binder design as well as the application of pulsed potential
Microstructural evolution and phase transitions in porous Ta/Cu alloys under high strain rates
No full textTantalum (Ta) and its alloys are widely used in electronics, dental implants, aerospace, and nuclear industries. Ta-based medical implants have also attracted considerable attention in recent years. However, challenges such as thermal conductivity, oxidation resistance, antibacterial properties, and the mismatch between bone and implant mechanical properties remain major concerns across various applications. The addition of alloying elements, such as copper (Cu), to Ta reduces bacterial adhesion in medical applications, while also improving thermal conductivity and oxidation resistance, making it beneficial for high-temperature environments. Furthermore, incorporating porosity into Ta-based materials mitigates stress shielding in implants, reduces weight, and enhances thermal dissipation in advanced engineering applications. While numerous studies have investigated the mechanical and physical properties of Ta-based alloys, the combined influence of porosity and alloying elements on the mechanical response of these biomaterials has not been systematically studied. This study employs molecular dynamics (MD) simulations to analyze the mechanical response and microstructural evolution of porous Ta/5 wt% Cu alloys under uniaxial tensile loading. Our results demonstrate that optimizing strain rates and introducing pores can modulate the mechanical characteristics of Ta/Cu alloys. Increasing the strain rate from 5 × 108 to 5 × 1011 s− 1 enhances properties due to the rapid BCC-to-FCC phase transformation at high strain rates, while increasing porosity from 0 to 10% reduces yield stress and elastic modulus by 12% and 14%, respectively. Moreover, the influence of porosity on deformation-induced microstructural transformations, such as twinning behavior and crystallographic changes, is examined. The study offers insights into designing porous Ta-based alloys with improved mechanical performance and microstructural characteristics
Indigenous Spirituality, Health, and Well-Being in the Young: Yarns With the Victorian Aboriginal Community
No full textThe extant literature has scant detail about everyday spiritual practices that aid Indigenous young people. This paper systematically explores Indigenous Spirituality, health, and well-being through Elder-governed yarns conducted via Zoom with 44 Aboriginal Elders, Healers, and Senior and Junior people involved in health and well-being of the Victorian Aboriginal community. These yarns were analyzed through an innovative, constructivist, multi-perspectival discursive grounded theory method. Key findings are that Spirituality is crucial for health and well-being, leading to a clear mind and at-peace "center" in a person. Aboriginal spiritual practices reflect the unique characteristics and essential rhythms of Country. Spiritual development is incremental and increases the obligations and responsibilities a person has to community and Country and leads to increased caring for Country. This paper provides rich detail about practical spiritual techniques to aid Indigenous young people and their kinship networks. It has the potential to shape future policy