Recent publications
In a recent paper, we proposed a Personalized Patient Preference Predictor (P4), building on earlier work by Rid, Wendler, and colleagues. The P4 is a hypothetical computer program that would, in the context of surrogate decision-making (e.g., following a substituted judgment standard), use generative AI models to infer a patient’s underlying values and preferences and, on that basis, predict which treatment option they would choose in the current situation. Such AI models, we suggested, could be “fine-tuned” on various preexisting data or materials produced by, or otherwise pertaining to (e.g., including information about), the patient considered as a unique individual.
The transition to chaos in the subcritical regime of counter-rotating Taylor-Couette flow is investigated using a minimal periodic domain capable of sustaining coherent structures. Following a Feigenbaum cascade, the dynamics are found to be remarkably well approximated by a simple discrete map that admits rigorous proof of its chaotic nature. The chaotic set that arises for the map features densely distributed periodic points that are in one-to-one correspondence with unstable periodic orbits (UPOs) of the Navier-Stokes system. This supports the increasingly accepted view that UPOs may serve as the backbone of turbulence and, indeed, we demonstrate that it is possible to reconstruct every statistical property of chaotic fluid flow from UPOs.
We investigate the assembly of monodisperse polymer-coated polystyrene colloids during the evaporation of sessile drops on oil-coated substrates. In our system, the particles rapidly adsorb at the air–water interface, and...
Phenotypic plasticity is critical for animals to survive in our rapidly changing world, especially for species with low population densities. Standard hatchery procedures can assist some conservation programmes by producing large numbers of juveniles to be released into the wild. Yet we know surprisingly little about the impact that such standard, minimalistic hatchery settings have on the development of important behaviours and life-history traits of the animals. Here, we fill this gap by testing whether and how early-life exposure to different environmental conditions alters the development of ecologically relevant behaviours and life-history traits of the European lobster (Homarus gammarus)—one of the most harvested species in the Mediterranean. We used the progeny of wild-caught females and manipulated—in a full factorial design—the environmental complexity of the individual enclosures and the level of perceived predation risk. We repeatedly quantified key behaviours (activity, shelter use and aggressiveness) and life-history traits (carapace length and intermoult period) of individuals throughout their early development, capturing both mean and individual-level variation across treatments. Our results offer solid evidence that standard hatchery settings compromise the development of important behavioural and life-history traits of lobsters and even alter their behavioural plasticity—probably reducing the effectiveness of conservation programmes.
Objectives
To explore the correlations/relationships between foot posture, equity and diversity, employment, and time in Barbie Land.
Design
A retrospective audit of the Barbie population (or their data from online catalogues) using a customised FEET system. That is Foot posture (flat or equinus); Equity (diversity and inclusion (EDI)); Employment (fashion vs employed); and Time period (decade of manufacture).
Setting
Barbie Land (Online Barbie catalogues of doll types).
Participants
2750 Barbies and friends who lived in Barbie Land between 1959 to June 2024.
Main outcome measures
Over time there was a decreased prevalence in equinus foot posture from 100% in the first time period to 40% in the last. Barbie’s flat foot posture had a very strong positive correlation with employment (r = 0.89, 95% Confidence Interval (95%CI) = 0.50 to 1.29), and time point (r = 0.85, 95%CI = 0.40 to 1.31), while equinus foot posture had a very strong positive correlation with fashion (r = 0.99, 95%CI = 0.87 to 1.11). Similarly, equity (diversity) had a very strong positive correlation with fashion (r = 0.98, 95%CI = 0.82 to 1.15), and strong positive correlation with employment (r = 0.79, 95%CI = 0.26 to 1.33).
Conclusion
Barbie’s equinus foot posture is directly related to her high heel wearing. Barbie models her footwear choice based on task demands, being flat footed and wearing flat shoes when she needs to work on her feet, be physically active or more stable. Given Barbie is known to reflect societal norms, we contend this is most likely true for most high-heel wearers. While Barbie has moved with the times, it appears footwear health messaging about high heel wearing needs to catch up. Health professionals castigating high heels through public messaging, should remember that emphasising health benefits consistently drives positive behaviour change, over highlighting negative consequences. Barbie clearly makes sensible determinations regarding her body autonomy; high heel wearers should have that same ability.
Polysemy is the linguistic phenomenon where a word has more than one sense. Polysemy is important to philosophy. This article considers four related strands of discussion in philosophy in which polysemy plays a crucial role: (i) Chomsky's argument against externalist semantics; (ii) copredication and zeugma; (iii) semantic accounts of philosophically significant terms; and (iv) metaphysical debates.
Introduction
The detailed anatomy visualization with magnetic resonance (MR)‐guided radiotherapy is particularly attractive for abdominal treatments, but patient respiratory motion can compromise image quality. The “navigator technique” produces high‐quality 3D images, triggered by diaphragm displacement, in exhale phase only. The gold standard for planning is 4D imaging, which visualizes the lesion for all breathing phases. When 4D imaging is not available, an alternative is using 3D imaging combined with motion information from cine‐MR.
Methods
This work investigates two alternative internal target volume (ITV) generation methods and compares them with the original treatment 4DCT imaging ITV. Datasets were analyzed from 10 upper abdominal patients that originally had been treated with a 4DCT‐based ITV. In addition to the 4DCT, these patients received an exhale MR and cine‐MR scans prior to treatment. An MR‐CT‐compatible motion phantom was also used to compare the two alternative ITV methods with the clinical 4DCT method. The first ITV method uses “margins expansion” (ME method) asymmetrically. The second method duplicates the exhale gross tumor volume (GTV) and shifts it to the positions of the average inhale GTV and mid‐position GTV. The ITV is the “Boolean combine” (BC method) of the three displaced GTVs. The ME and BC methods were compared with the clinical 4DCT method using the Dice similarity coefficient (DSC) to determine the impact of approximating the true GTV trajectory and neglecting deformation.
Results
The ITV DSC ranges were 73%–96% for the ME method and 76%96% for the BC method. The BC approach created smaller treatment volumes than the ME method and more closely resembled the 4DCT margin for cases with larger motion and a significant component in the anterior–posterior direction.
Conclusions
An exhale MR combined with cine‐MR can be used to simply create an ITV for adaptive MR‐guided radiotherapy. For small lesions with larger anterior motion, the Boolean Combine method is the more accurate method.
For multi-scale differential equations (or fast–slow equations), one often encounters problems in which a key system parameter slowly passes through a bifurcation. In this article, we show that a pair of prototypical reaction–diffusion equations in two space dimensions can exhibit delayed Hopf bifurcations. Solutions that approach attracting/stable states before the instantaneous Hopf point stay near these states for long, spatially dependent times after these states have become repelling/unstable. We use the complex Ginzburg–Landau equation and the Brusselator models as prototypes. We show that there exist two-dimensional spatio-temporal buffer surfaces and memory surfaces in the three-dimensional space-time. We derive asymptotic formulas for them for the complex Ginzburg–Landau equation and show numerically that they exist also for the Brusselator model. At each point in the domain, these surfaces determine how long the delay in the loss of stability lasts, that is, to leading order when the spatially dependent onset of the post-Hopf oscillations occurs. Also, the onset of the oscillations in these partial differential equations is a hard onset.
The development of interstitial lung diseases (ILDs) involves a complex interplay between genetic and environmental factors. These factors contribute to the risk of development of disease, disease trajectory, and response to treatment. Understanding the contribution of each and the interaction between these effects will help better understand the pathogenesis and risk of ILDs, and in the future how they can aid precision medicine.
Background
Postpartum haemorrhage (PPH) is the leading cause of maternal mortality. Uterotonics are the mainstay of PPH prevention.
Objectives
To compare the efficacy of misoprostol and oxytocin for the prevention of PPH and to evaluate the trustworthiness of these randomised controlled trials (RCTs).
Search Strategy and Selection Criteria
Seven databases were searched for peer‐reviewed literature meeting the inclusion criteria of RCTs comparing misoprostol and oxytocin for the prevention of PPH.
Data Collection and Analysis
Data were collected by two independent reviewers. Individual participant data (IPD) were meta‐analysed for outcomes PPH ≥ 500 and ≥ 1000 mL. RCTs that did not share IPD were classified as trustworthy or not, and aggregate data were meta‐analysed according to trustworthiness.
Main Results
Of 79 eligible RCTs, 10 (12.7%) provided IPD, of which 6 were included. Analysis of IPD showed PPH ≥ 500 mL to be significantly higher in the misoprostol than in the oxytocin group (2022 participants, aOR 1.84, 95% CI 1.43–2.34). For PPH ≥ 1000 mL, analysis of IPD showed that misoprostol and oxytocin were comparable (2022 participants, OR 1.14, 95% CI 0.68–1.91).
Of the 69 studies that did not provide IPD, 23 (33.3%) were assessed as trustworthy. Analysis of trustworthy data (IPD and 23 aggregate data RCTs) showed no difference between misoprostol and oxytocin for PPH ≥ 500 mL (24 334 participants, OR 1.01, 95% CI 0.69–1.49), while misoprostol was associated with a significantly increased risk of PPH ≥ 1000 mL compared to oxytocin (25 249 participants, OR 1.36, 95% CI 1.16–1.59).
Conclusions
Of 79 RCTs comparing misoprostol and oxytocin for the prevention of PPH, 36.7% met trustworthiness criteria. Oxytocin is comparable to misoprostol for preventing PPH and may be superior for preventing severe PPH.
Two‐electron water oxidation reaction (2e‐WOR) to produce hydrogen peroxide (H2O2) is an attractive anode reaction with several merits. It can be paired with several large‐scale cathode reactions that produce valuable chemical substances in an electrochemical cell. However, high‐performing and reliable 2e‐WOR anodic catalysts are yet to be fully developed. In this work, a rationally designed, inexpensive, robust, and selective graphite catalyst electrode is presented, made by following the key principle mechanisms of 2e‐WOR. First, an aerophilic graphite‐based electrode is created to leverage the challenges posed by the four‐electron WOR, where the generated O2 from this reaction is kept onto the electrode surface to shift the O intermediates binding on graphite in the direction of improved H2O2 generation. An initial improvement in H2O2 selectivity of seven fold is observed, albeit with no improved H2O2 generation rates. The stunted H2O2 generation is ascribed to poor activity from pristine graphite, courtesy of less active sites and low intrinsic O2 binding in the electrolyte environment. Second, to improve and balance graphite's activity and selectivity, the structure of graphite is altered via different elemental doping (with N, S, B, and P atoms), a method that allows the retention of the O2 on the graphite surface. The super‐aerophilic B‐doped graphite catalyst (optimum) reaches a maximum Faraday efficiency (FE) of 60.6 ± 2.6% with a production rate of 26.7 ± 0.6 µmol min⁻¹ cm⁻² (85.9 ± 2.2 mA cm⁻² partial current density) and excellent stability of over 120 h. In tandem, cathodic H2 co‐production is demonstrated with an FE of above 90%. This approach demonstrates a rational approach to designing inexpensive and robust 2e‐WOR anode catalysts for H2O2 and the possibility of its use in chemical co‐production at the cathode.
BNIP3 and NIX are the main receptors for mitophagy, but their mechanisms of action remain elusive. Here, we used correlative light EM (CLEM) and electron tomography to reveal the tight attachment of isolation membranes (IMs) to mitochondrial protrusions, often connected with ER via thin tubular and/or linear structures. In BNIP3/NIX-double knockout (DKO) HeLa cells, the ULK1 complex and nascent IM formed on mitochondria, but the IM did not expand. Artificial tethering of LC3B to mitochondria induced mitophagy that was equally efficient in DKO cells and WT cells. BNIP3 and NIX accumulated at the segregated mitochondrial protrusions via binding with LC3 through their LIR motifs but did not require dimer formation. Finally, the average distance between the IM and the mitochondrial surface in receptor-mediated mitophagy was significantly smaller than that in ubiquitin-mediated mitophagy. Collectively, these results indicate that BNIP3 and NIX are required for the tight attachment and expansion of the IM along the mitochondrial surface during mitophagy.
Violence against women is pervasive. An estimated 25% of Australian women (≥ 15 years) have experienced intimate partner violence. Recent cases of homicidal burn violence perpetrated against Australian women have shocked the nation. However, little evidence exists about the burden of burn violence against Australian women. This study describes and compares the frequency, sociodemographic profile, injuries, and outcomes of women admitted to Australian burn centres with burns from suspected violence with women with unintentional burns.
Data were extracted from the Burns Registry of Australia and New Zealand for women (≥ 18 years) admitted to Australian burn centres between 2009 and 2022, with burns from suspected violence or unintentional burns. Socio-demographic profiles, injury, and in-hospital outcomes were compared. To further explore group differences, 155 women from each group were propensity score matched (one-to-one basis), with subsequent group comparisons made.
Of 6262 women meeting inclusion criteria, few reported burns from suspected violence (2.5% versus 97.5%). Women with burns from suspected violence were younger (median 36 vs 43 years), greater proportions sustained flame burns (38.1% vs 25.3%) involving petrol (80.0% vs 38.0%), their injuries more likely involved their head (42.3% vs 16.4%), and a greater proportion died (4.5% versus 1.5%). Perpetrators were most often intimate partners.
Our study contributes to emerging international literature demonstrating the confronting nature and consequences of burn violence against women. Building capacity amongst burn centre teams to identify and respond to suspected burn violence will better protect Australian women and aligns with national plans to end violence against women.
Introduction
Despite successful public health campaigns, tobacco use persists as a major cause of preventable illness and death. While tobacco taxation is recognized as an effective control strategy, concerns remain about potential financial strain on lower socioeconomic groups. This study investigates the relationship between household tobacco expenditure and financial stress in Australia, a country with high tobacco taxes and declining smoking rates.
Methods
Household data from the 2015-16 Australian Household Expenditure Survey were analysed (N=10,036). Financial stress was measured using a scale based on nine self-reported indicators. Respondents were asked to report if their household had experienced any of these difficulties, e.g. inability to pay utility bills or going without meals. Negative binomial regression models assessed the association between tobacco expenditure share and financial stress, adjusting for sociodemographic factors, household wealth, and other expenditures.
Results
Financial stress was more prevalent among households that did (45.0%; (95% CI: 42.5, 47.5)) versus did not (25.4%) purchase tobacco. All levels of tobacco expenditure were significantly associated with higher financial stress bivariably, after controlling for covariates. For instance, households in the second-lowest tobacco expenditure share quintile had a higher mean financial stress score than non-purchasing households (RR=1.59, CI, 1.36, 1.85, p<0.001).
Discussion
In Australia, financial stress is prevalent among tobacco-purchasing households and household tobacco expenditure is significantly associated with increased financial stress even at modest levels of spending, i.e. the lower quintiles of tobacco expenditure. These findings underscore the need for targeted policies to mitigate financial strain and support smoking cessation among vulnerable populations.
Implications
This study found that the prevalence of financial stress is higher in Australian households that purchase tobacco, regardless of their spending on tobacco. Although tobacco price increases reduce overall tobacco use, our study shows that increased prices exacerbate strain among financially disadvantaged smokers. Further research into associations between financial well-being and tobacco use is needed, both nationally and internationally. Longitudinal research should also examine the longer-term health and economic impacts mediated by financial stress.
Data linkage is a powerful tool for understanding the multifaceted needs and priorities of mental health care from the perspective of users and providers. Its potential remains underutilised in Australian settings – the Productivity Commission Inquiry into Mental Health in 2020 highlighted a significant gap: routinely collected administrative data are seldom leveraged in mental health research and service evaluation. In this manuscript, we provide insights into how data linkage has been used in mental health research, the type of questions that can be addressed, the steps involved in conducting data linkage research and the benefits and limitations of the use of this methodology. We propose crucial recommendations for advancing this field including: enhancing education for stakeholders (including the public, data custodians, ethics committees and policy makers); fostering stronger collaborative relationships with individuals with lived experiences throughout the research journey; improving infrastructure and resources for data linkage activities and linking data across sectors to address complex meaningful research questions. Data linkage is not just a method but a critical strategy to transform mental health research and service evaluation, ensuring more informed, effective and holistic mental health care.
Background
Aquatic foods are micronutrient-rich and utilised by coastal communities across the globe. However, the contribution of aquatic foods sourced from mangroves to nutrient intake is relatively unknown, despite thousands of people reliant on their resources in coastal regions across the globe. This case study aimed to quantify the nutrient contribution that aquatic foods make to mangrove fishers’ household dietary requirements in a community in West Kalimantan, Indonesia.
Methods
A seven-day household weighed food record of all aquatic food consumed was conducted twice to capture seasonal variability, in the wet (n = 59) and dry seasons (n = 54). Records were analysed using nutrition composition datasets for finfish and shellfish. The contribution aquatic foods make to the recommended nutrient intake (RNI) was described for seven nutrients: calcium, iron, selenium, zinc, vitamin A, omega-3 essential fatty acids and protein. The total quantity of each species consumed for each season was determined to calculate the average per-person nutrient intake from each species and from all aquatic food species combined. We then compared these to each of the RNI sex and age categories and aggregated it to present an average (%) RNI for the total sample and by season.
Results
Households consumed more meals containing aquatic food in the dry season (390 meals) compared to the wet season (337 meals). Aquatic foods contributed to all seven nutrients analysed, mostly to the RNIs for selenium (127% wet season and 193% dry season), protein (27% wet season and 35% dry season), omega-3 essential fatty acids (21% in both seasons), and zinc (10% wet season and 17% dry season). Contribution to iron reduced from 11 to 10% between the wet and dry seasons and increased from 8 to 10% for calcium and 4–7% for vitamin A between the wet and dry seasons respectively.
Conclusions
Our findings indicate that mangrove aquatic foods provide important nutrients in local seasonal diets in West Kalimantan. Given the nutritional challenges Indonesia faces, sustaining local engagement with mangroves as a food system should be considered in the aquatic foods discourse and nutrition projects, as well as mangrove conservation and management strategies.
Background
There is an urgent need for improved treatments for Chagas disease, a neglected tropical infection caused by the protozoan parasite Trypanosoma cruzi. Benznidazole, the first line therapy, has severe limitations such as poor tolerability and variable efficacy in the chronic stage of infection. To optimize dosing regimens, a better understanding of the pharmacokinetic/pharmacodynamic (PK/PD) relationship for benznidazole is crucial. This study aimed to characterize the population pharmacokinetic properties of benznidazole in mice and investigate the relationship between exposure and antitrypanosomal activity in T. cruzi infected mice.
Methodology/principal findings
Antitrypanosomal activity was assessed in 118 BALB/c mice with chronic-stage T. cruzi infection, utilizing highly sensitive in vivo bioluminescence imaging (BLI). Benznidazole was administered at doses ranging from 10 to 100 mg/kg for 5–20 days. The pharmacokinetic properties of benznidazole were evaluated in 52 uninfected BALB/c mice using nonlinear mixed-effects modeling. The relationship between simulated benznidazole exposure and sterile parasitological cure in the BLI experiments was evaluated by logistic regression and partial least squares – discriminant analysis.
Benznidazole pharmacokinetics in mice were well described by a one-compartment disposition model with first-order absorption, with higher doses associated with slower absorption. Univariate logistic regression revealed a significant correlation between drug exposure and the probability of parasitological cure. Total plasma exposure, time above IC90 and peak plasma concentration were all strongly associated with efficacy, provided that benznidazole was administered for at least 5 days.
Conclusions/significance
This is the first study to successfully quantify the dose-response relationship for benznidazole in T. cruzi-infected mice using preclinical BLI data. Our results underscore the complexity of distinguishing PK/PD drivers of efficacy due to high collinearity between PK/PD index parameters, and we propose dose-fractionation studies for future research. Studying the PK/PD relationship using the BLI model provides valuable insights, aiding hypothesis generation through endpoint assessment of parasite infection.
Surgical site infections are common, result in increased patient morbidity and mortality, and increase the economic burden to society. Anesthesiologists play a key role in perioperative infection prevention, with data suggesting that evidence-based measures can significantly reduce the incidence of these infections. This systematic review aimed to identify and compare current recommendations for the maintenance of homeostasis in surgical site infection prevention guidelines. Eight surgical site infection prevention guidelines published in the past 10 yr were identified. There was broad consensus regarding the importance of optimizing intraoperative homeostasis to reduce infections. However, there was substantial heterogeneity in both the studies cited and the specific recommendations provided regarding maintenance of oxygenation, normovolemia, normothermia and glycemic targets. High-quality randomized controlled trials are required to close existing knowledge gaps, with adaptive platform trials likely to play a key role in improving the current evidence base for preventing surgical site infection.
The widespread success of electronic transistors is partly due to their ability to be modeled using equivalent circuits, which not only enables detailed analysis and efficient design but also provides greater insight for designers, facilitating the development of complex electronic systems. The Ebers–Moll model, for example, is a widely used large-signal equivalent circuit that replicates the operational characteristics of bipolar junction transistors. Similar to electronic transistors, research on quantum thermal transistors has gained considerable attention in recent years; however, minimal focus has been placed on developing equivalent circuit representations. Drawing inspiration from equivalent models of electronic transistors, our study proposes an equivalent model for a quantum thermal transistor built on a strongly coupled qubit–qutrit–qubit architecture. This configuration allows replication of its transistor behavior using a diode-based equivalent model, leveraging its property of splitting the qutrit into two individual qubits. The proposed quantum thermal diode-based equivalent model closely mirrors the diode-based representation of an electronic transistor. Using frameworks of open quantum systems and the quantum Markovian master equation, along with the Born approximation and rotating wave approximation, we conduct a comprehensive analysis and comparison of our quantum thermal diode-based equivalent model with an established quantum thermal transistor model. Furthermore, we discuss the intrinsic internal coupling between the two diodes and determine the optimum coupling strength necessary for efficient heat amplification. This equivalent model provides greater insight into the analysis of quantum thermal transistors and significantly contributes to the advancement of nanoscale thermal circuit designs.
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Melbourne, Australia
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Professor Margaret Gardner AO
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