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The limits of promoting pleasure: Desiring-assemblages and HIV pre-exposure prophylaxis
No full textHIV pre-exposure prophylaxis (PrEP) is said to have transformed pleasure and sexual practices in myriad ways. This article draws on interviews with PrEP users in Australia who had paused, stopped, or switched PrEP use in order to explore the varied affects and experiences of PrEP in relation to different dosing strategies. Drawing on the concept of ‘desiring-assemblages’, we considered ‘what can a body with PrEP do?’. Our analysis affirms PrEP as transformative, enabling freedom through reduced or removed fear of HIV transmission. However, participant accounts also suggested that PrEP has been normalised as an ordinary part of sexual cultures, with some indicating that PrEP use was felt as obligatory or ambivalent. Daily and nondaily dosing also potentiated different flows of desire and connections, remaking what PrEP is and can be in participants’ lives in ways that trouble the idea that PrEP consistently facilitates pleasure. PrEP dosing was framed by discussion of changes to one’s sense of self and future priorities, and through ideas about freedom, pleasure, shame, safety, obligation, fitting in, waste, and potential. While PrEP is increasingly promoted through messaging linked to ‘pleasure’, instead of earlier discourses of ‘risk’, a pleasure-centric focus may delimit understandings of how PrEP can produce multiple sexual lives and practices, including the mundane aspects of sex and pleasure. To appeal to a range of potential PrEP users, health promotion should emphasise the different possibilities for PrEP – it’s potential for pleasure, its critical role in preventing HIV, and its normative mundanity
Carbon-Based Electrocatalysts for Ammonia Synthesis: Data-Driven Design and Mechanistic Insights
No full textThe growing global challenges of energy crisis, climate change, and environmental pollution have accelerated the demand for sustainable energy production and green chemical manufacturing. Nitrogen-containing chemicals, particularly ammonia, serve as essential building blocks for modern industry, agriculture, and energy storage. However, conventional industrial ammonia synthesis processes, such as the Haber-Bosch (ammonia production) routes, suffer from high energy consumption and substantial pollutant emissions.
In this context, electrocatalytic ammonia synthesis approaches, including nitrogen reduction reaction (NRR) and nitrate reduction reaction (NO3RR), have emerged as promising alternatives. These approaches enable ammonia synthesis under ambient conditions by utilising renewable electricity while simultaneously offering routes for pollutant remediation. Nevertheless, the discovery of high-performance catalysts poses a significant challenge. Traditional catalyst design relies on inefficient trial-and-error approaches, which are time-consuming and resource-intensive. Moreover, the complexity of reaction pathways and the difficulty in experimentally characterising key intermediates severely limit the mechanistic understanding and rational design of catalysts.
To address these challenges, this dissertation focuses on the theoretical design and mechanistic investigation of electrocatalysts for ammonia synthesis reactions, employing density functional theory (DFT) and high-throughput screening. These methods enable the in-depth study of reaction pathways, activation barriers, and electronic structure changes, offering valuable insights into the behaviour of catalytic active sites throughout the reaction process. This study focuses on carbon-based catalyst systems, including heteroatom-modified single-atom catalysts and metal-free B, N co-doped carbon-based catalysts. Key factors such as local coordination, electronic modulation, spin-state regulation, and defect engineering on catalytic activity are comprehensively investigated across NRR and NO3RR. Furthermore, the integration of DFT with high-throughput screening and data-driven methods is explored to accelerate catalyst discovery and deepen mechanistic insights. The findings contribute to the fundamental understanding of electrocatalytic ammonia synthesis mechanisms and provide valuable theoretical guidance for the rational design of efficient, sustainable, and environmentally friendly catalytic systems
Does Stakeholder Outrage Determine Executive Pay?
No full textAbstract An unprecedented number of firms announced CEO salary reductions at the onset of the coronavirus pandemic. We document that the total compensation for these CEOs did not actually decrease but was instead restructured, leading to a marked increase in opaque components of compensation. These adjustments align with the managerial power view of executive pay setting, whereby heightened stakeholder outrage prompts greater camouflaging of compensation to avoid scrutiny. We further show that this pattern of compensation adjustments predominantly occurred in firms with powerful CEOs, weak institutional investor monitoring, and poorer governance quality
Evidencing work: implementing HIV pre-exposure prophylaxis and on-demand dosing in Australia
No full textHIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs to prevent HIV infection, was initially implemented in Australia as a daily regimen, transforming HIV prevention. However, the process of implementation, and key shifts in the delivery of PrEP, such as the introduction of on-demand (non-daily) dosing, are not well understood. This study aimed to understand how key stakeholders put PrEP into practice, and the ‘evidencing work’ that underpinned these processes. Evidencing work refers to how actors mobilise ‘local orders of evidence’ to understand and assess how an intervention, like PrEP, performs in its local context. We conducted 21 interviews in 2021–2022 with key stakeholders representing research, clinical practice, policymaking, health education and promotion, and community engagement. The analysis shows how stakeholders worked with and understood evidence, the prominence of (and departure from) clinical guidelines, and the growth in and recognition of on-demand dosing. Participants described translational, authorising, and localising evidencing work, overlapping practices necessary to create ‘evidence enough’ to proceed with implementation. The generation of national, local, and peer- and expertise-based evidence was particularly important to reassure participants that PrEP use was safe and effective in Australia, and to provide evidence that on-demand dosing could be successfully practiced. Encouraging localising evidencing work with less familiar prescribers (e.g. sharing peer-, patient- and expertise-based evidence about PrEP) could enable PrEP rollout and support for different dosing regimens, such as on-demand dosing
Psychotropic medications and their interactions with subcortical brain volume in bipolar disorder: An ENIGMA mega-analysis
No full textMRI studies in bipolar disorder (BD) have yielded inconsistent findings, partly due to the varied use of psychotropic medications. This study utilised a mega-analysis approach, accounting for concurrent medication status (syndrome-based and Neuroscience-based Nomenclature (NbN) classifications), in order to assess the association of medication status with subcortical brain volumes in BD. Data from 2,664 BD patients and 4,065 controls (CN) were pooled from 34 research groups as part of the ENIGMA Bipolar Disorder Working Group. Standardized ENIGMA protocols were used to measure subcortical brain volumes. Linear-mixed-effects regression evaluated the association between psychotropic medications and subcortical volumes, and moderation analyses explored interactions. Medication-free patients (n = 410) showed mild ventricular enlargement (d = 0.07) and increased putamen volume (d = 0.06) compared to CN. Patients taking psychotropic medications exhibited smaller subcortical volumes (d = -0.06 to -0.11) and larger ventricles (d = 0.11 to 0.19). Use of antiepileptic and antipsychotic medications was associated with smaller hippocampal and thalamic volumes (d = -0.07 to -0.14), while NbN classification indicated that the categories of ‘valproate’ and ‘dopamine and other monoamine receptor antagonists’ are key variables when considering volume differences between BD and CN. Concurrent lithium use weakened the negative association between antiepileptic use and hippocampal volume (β = 0.19, q = 0.038) in patients. Medication status is associated with altered subcortical brain volumes in BD. The NbN classification provides a useful framework for future studies, emphasizing the need for comprehensive longitudinal research to further unravel complex clinical-pharmacological-neurobiological interactions in BD
Design and development of novel isoflavonoid anti-inflammatory and anticancer agents
No full textCancer and chronic inflammatory diseases are leading causes of death and disease burden worldwide.
Cancer is the second leading cause of death globally, accounting for nearly 10 million deaths in 2020 alone.
Inflammation plays a central role in disease onset, progression, and resistance, and has been implicated in over 50%
of all deaths, including approximately 20% of cancers. Persistent mortality and treatment resistance underscore the
urgent need to understand and develop novel treatment options targeting the key drivers of these diseases.
The aim of this thesis was to develop anticancer and anti-inflammatory agents derived from isoflavonoid and related
scaffolds to target key oncogenic and inflammatory signalling pathways such as TBK1/STING, CDK7/MYC and
ERα/ERβ. Computational modelling was utilised for compound design, screening and optimisation. In silico studies
led to a focus on C6 and C7 modifications of the isoflavene idronoxil (IDX). C6 modification resulted in anti-
inflammatory leads with potent TBK1 inhibitory potency (IC50 = 0.13 µM). The mechanism of the lead compounds
was confirmed with multiple biological assays, and the viability of the lead as an anticancer agent was also evaluated
through synergistic cytotoxicity studies. A further series of C6 modifications resulted in promising compounds with
cytotoxic potency in acute myeloid leukemia. Similar modifications were also compared on other heterocyclic
scaffolds but showed inferior activity to isoflavene analogues. Isoflavene leads were shown in biological assays to
inhibit the superoncogenic target MYC by suppressing CDK7 activity.
Structure-based design was further employed to attempt to modulate the estrogenic properties of isoflavonoids for
the treatment of estrogen positive cancers. In this respect, two anticancer leads were obtained with low micromolar
cytotoxicity against breast cancer cell lines (IC50 = 1.5 µM in T-47-D). Mechanistic analysis was also investigated
through enzymatic assays. In addition, various strategies for incorporating fused ring structures to the C6 and C7
positions of the IDX A ring were investigated, with the objective of further enhancing anticancer or anti-inflammatory
properties. Compounds were screened across various cancers including neuroblastoma, prostate, and breast cancers.
Put together, this work expands the therapeutic potential and SAR of isoflavonoids against cancer and inflammatory
diseases
Effect of Iron Oxidation on the Activity of Platinum-Decorated Iron Nanoparticles for the Hydrogen Evolution Reaction
No full textPlatinum decorated on iron nanoparticle catalysts holds significant promise for the electrochemical hydrogen evolution reaction (HER). The metal combination aims to leverage a bifunctional mechanism, where the oxophilic iron facilitates water dissociation, while hydrogen evolution occurs on the platinum sites. However, the inherent susceptibility of Fe to oxidation can undermine the catalyst stability and efficiency. To directly understand this, our study investigates the impact of Fe nanoparticle oxidation on the HER activity of deposited Pt islands, achieved through the direct growth of face-centered cubic Pt islands on Fe nanoparticles. These Pt–Fe heterostructures were evaluated for the HER, revealing a significantly detrimental impact of iron support oxidation on Pt activity. This highlights the critical challenge of substrate oxidation for the performance of Pt–M bimetallic HER catalysts. Our work underscores the necessity of mitigating support oxidation to fully realize the potential of these materials for clean energy applications
Indonesia's billion dollar fuel fraud exposes deep corruption crisis
No full textThis article provides insights into what Indonesia's largest corruption scandal to date can tell us about the overall state of anticorruption efforts in contemporary Indonesi
‘They have a really good way of getting it to the kids’: evaluation of a child injury prevention programme in Walgett, New South Wales
No full textBackground Aboriginal community-led programmes are likely to be most effective in prevention of injury, but more evaluation is needed. This article examined participating family and community stakeholder views of the Child Injury Prevention Partnership (CHIPP) programme delivered within an existing playgroup at the Walgett Aboriginal Medical Service. Methods This codesigned, mixed-methods evaluation adopted a decolonising Indigenous methodological approach. Aboriginal staff members provided weekly reflections on implementation, and family participation data were documented. Parents/carers provided regular feedback and, along with community stakeholders, participated in postprogramme research yarning. Results During 2021, playgroup sessions were facilitated by locally trained Aboriginal early childhood staff, who offered 2 hourly sessions twice a week. CHIPP implemented safety education for both adults and children through safety yarns and resources to take home focused on water, home and road safety. Parent/ carer and stakeholder research yarns revealed six themes: CHIPP was feasible and culturally acceptable for families; Playgroup enabled supportive, holistic delivery of safety messages to adults and children; CHIPP provided information and resources to equip parents and carers to help teach safety at home; Approach to teaching infants and preschoolers safety was based on building confidence through fun, engaging, age-appropriate activities; Programme topics and content were relevant for families and COVID-19 impacted programme delivery but pivoted temporarily to remote delivery. Conclusions The CHIPP programme was feasible, accessible, acceptable and demonstrated initial beneficial impact, despite implementation challenges during the COVID-19 pandemic, offering suggestions to inform other child injury prevention programmes in Aboriginal community-controlled settings
The effect of an Iyengar yoga-based exercise programme versus a seated yoga relaxation programme on falls in people aged 60 years and older (SAGE): a pragmatic, two-arm, parallel randomised controlled trial
No full textBackground: Exercises targeting balance and strength are proven to prevent falls. Yoga is growing in popularity and can improve balance and mobility in older adults, but its effects on falls have not been rigorously tested. In this study, we aimed to compare the effects of Iyengar yoga-based exercise and seated relaxation yoga on the rate of falls among older adults. Methods: This pragmatic, two-arm, parallel randomised controlled trial recruited Australian community-dwelling people aged 60 years and older who were not currently practising yoga and who lived independently. Participants were randomly assigned (1:1) to the intervention (Iyengar yoga-based exercise) or control (seated relaxation yoga) group using a computer-generated sequence. Participants and yoga instructors were unmasked, but research staff verifying falls data and assessing goal attainment were masked to group allocation. Intervention participants received 80 supervised, 1-h, twice-weekly yoga classes over 12 months, and were encouraged to undertake unsupervised practice on 2 additional days per week. Control participants attended two 1-h supervised workshops focused on seated breathing and stretching. Most classes were held online due to the COVID-19 pandemic. The primary outcome was fall rate per year. Secondary outcomes were mental wellbeing, physical activity, quality of life, balance self-confidence, physical function, sleep quality, pain, and goal attainment, all assessed in the intention-to-treat population. The study protocol was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619001183178). Findings: Between Oct 3, 2019, and Oct 28, 2021, 2182 older adults expressed their interest in participating, 810 were assessed for eligibility, 110 were excluded, and 700 were randomly assigned to either the Iyengar yoga exercise programme or the control group (seated yoga relaxation programme; 350 participants per group). The mean age of participants was 67 years (SD 5·2), and 570 (81%) were female and 130 (19%) were male. Six intervention participants reported musculoskeletal-related adverse events associated with the yoga programme, and no serious adverse events occurred. Contrary to expectations, there was a higher fall rate in the intervention group than in the control group (0·87 vs 0·64 falls per person-year; incidence rate ratio 1·33 [95% CI 1·01–1·75; p=0·044]). The intervention improved the number of hours per week of planned physical activity (mean difference 0·96 h per week [95% CI 0·43–1·49]; p<0·0001), self-reported balance confidence (mean difference 2·94 [0·60–5·28]; p=0·014), and goal attainment (mean difference 0·60 [0·26–0·94]; p=0·0006). No significant between-group differences were identified for other secondary outcomes. Interpretation: This Iyengar yoga-based programme should not be recommended for fall prevention in its current form. Modified programmes with dynamic balance and fall prevention strategies warrant investigation. Funding: National Health and Medical Research Council