Recent publications
Advances in single cell technologies are allowing investigations of a wide range of biological processes and pathways in animals, such as the multicellular model organism Caenorhabditis elegans – a free-living nematode. However, there has been limited application of such technology to related parasitic nematodes which cause major diseases of humans and animals worldwide. With no vaccines against the vast majority of parasitic nematodes and treatment failures due to drug resistance or inefficacy, new intervention targets are urgently needed, preferably informed by a deep understanding of these nematodes’ cellular and molecular biology – which is presently lacking for most worms. Here, we created the first single cell atlas for an early developmental stage of Haemonchus contortus – a highly pathogenic, C. elegans-related parasitic nematode. We obtained and curated RNA sequence (snRNA-seq) data from single nuclei from embryonating eggs of H. contortus (150,000 droplets), and selected high-quality transcriptomic data for > 14,000 single nuclei for analysis, and identified 19 distinct clusters of cells. Guided by comparative analyses with C. elegans, we were able to reproducibly assign seven cell clusters to body wall muscle, hypodermis, neuronal, intestinal or seam cells, and identified eight genes that were transcribed in all cell clusters/types, three of which were inferred to be essential in H. contortus. Two of these genes (i.e. Hc-eef-1A and Hc-eef1G), coding for eukaryotic elongation factors (called Hc-eEF1A and Hc-eEF1G), were also demonstrated to be transcribed and expressed in all key developmental stages of H. contortus. Together with these findings, sequence- and structure-based comparative analyses indicated the potential of Hc-eEF1A and/or Hc-eEF1G as intervention targets within the protein biosynthesis machinery of H. contortus. Future work will focus on single cell studies of all key developmental stages and tissues of H. contortus, and on evaluating the suitability of the two elongation factor proteins as drug targets in H. contortus and related nematodes, with a view to finding new nematocidal drug candidates.
The fog computing paradigm is rapidly gaining popularity for latency-critical and bandwidth-hungry IoT application deployment. Meanwhile, MicroService Architecture (MSA) is increasingly adopted for developing IoT applications due to its high scalability and extensibility. For mission-critical IoT services in fog, reliability remains one of the most critical QoS requirements due to less dependability of fog resources. Granular microservices with independent deployment and scaling exhibit great potential in utilising resource-constrained fog resources to improve reliability through redundant placement. However, current research on service placement lacks reliability-aware holistic approaches that combine the MSA features and failure characteristics of fog resources under independent and correlated failures. Hence, we analyse MSA and formulate the reliability-aware placement problem by modelling composite services as k-out-of-n serial-parallel systems in a throughput-aware manner for placement under fog resource failures. Our proposed Reliability-aware Placement Method (RPM) is a hierarchical policy combining improved PSO and NSGA-II algorithms. We integrate it with Monte Carlo reliability calculations to produce redundant placements reaching a trade-off between reliability and cost. The performance results reveal that compared to the benchmarks, our algorithm shows significant improvements in reliability satisfaction (up to 25%) and time to first failure (up to 40%), thus providing a robust placement method.
The integration of software-defined networking (SDN) and cloud radio access networks (CRANs) into vehicular ad hoc networks (VANETs) presents intricate challenges to achieving stringent service level objectives (SLOs). These objectives include optimizing data flow and resource management, achieving low latency and rapid response times, and ensuring network resilience under fluctuating conditions. Traditional load balancing and clustering approaches, designed for more static environments, fall short in the dynamic and variable context of VANETs. This necessitates a paradigm shift towards more adaptive and robust strategies to meet these advanced SLOs reliably. This paper proposes a software-defined vehicular fog computing (SDFC) framework that refines resource allocation in VANETs. Our SDFC framework utilizes an intelligent controller placement that strategically positions decision-making entities within the network to optimize data flow and resource distribution. This placement is governed by a dynamic clustering algorithm that responds to variable network conditions, an advancement over the static mappings used by traditional methods. By incorporating parallel processing principles, the framework ensures that computational tasks are distributed effectively across network nodes, reducing bottlenecks and enhancing overall network agility. Empirical evaluations (testbed) and simulation results of our framework indicate a substantial increase in network efficiency: a 28% improvement in average response time, a 23% decrease in network latency, and a 25% faster convergence to optimal resource distribution compared to state-of-the-art methods. These improvements testify to the framework's ability to support the escalating demands of intelligent transportation systems and underscore its potential to refine operational efficacy within VANETs.
Edge computing (EC) enables low-latency services by pushing computing resources to the network edge. Due to the geographic distribution and limited capacities of edge servers, EC systems face the challenge of edge distributed denial-of-service (DDoS) attacks. Existing systems designed to fight cloud DDoS attacks cannot mitigate edge DDoS attacks effectively due to new attack characteristics. In addition, those systems are typically activated upon detected attacks, which is not always realistic in EC systems. DDoS mitigation needs to be cohesively integrated with workload migration at the edge to ensure timely responses to edge DDoS attacks. In this paper, we present EdgeShield, a novel DDoS mitigation system that leverages edge servers' computing resources collectively to defend against edge DDoS attacks without the need for attack detection. Aiming to maximize system throughput over time without causing significant service delays, EdgeShield monitors service delays and migrates workloads across an EC system with adaptive mitigation strategies. The experimental results show that EdgeShield significantly outperforms state-of-the-art solutions in both system throughput and service delays.
In the era emphasizing the privacy of personal data, verifiable federated learning has garnered significant attention as a machine learning approach to safeguard user privacy while simultaneously validating aggregated result. However, there are some unresolved issues when deploying verifiable federated learning in edge computing. Due to the constraint resources, edge computing demands cost saving measurements in model training such as model pruning. Unfortunately, there is currently no protocol capable of enabling users to verify pruning results. Therefore, in this paper, we introduce PrVFL, a verifiable federated learning framework that supports model pruning verification and heterogeneous edge computing. In this scheme, we innovatively utilize zero-knowledge range proof protocol to achieve pruning result verification. Additionally, we first propose a heterogeneous delayed verification scheme supporting the validation of aggregated result for pruned heterogeneous edge models. Addressing the prevalent scenario of performance-heterogeneous edge clients, our scheme empowers each edge user to autonomously choose the desired pruning ratio for each training round based on their specific performance. By employing a global residual model, we ensure that every parameter has an opportunity for training. The extensive experimental results demonstrate the practical performance of our proposed scheme.
A growing body of research focuses on individual environmental consciousness as an alternative and complement to regulatory and economic policy strategies for sustainable development. However, existing studies failed to explain the complex associations between individual environmental consciousness and conservation practices. This study constructs a framework of environmental prefigurative politics - technologies of the self (EPP-TS) to investigate how the mobilization of technologies of the self can lead to the subjectivization of individual environmental consciousness, thus enabling environmental prefigurative politics to shape specific conservation practices. First, this study argues that a range of technologies of the self, including discursive, incentive, and disciplinary technologies, are mobilized to subjectivize individual environmental consciousness. Second, the subjectivization of individual environmental consciousness prompts and institutionalizes the improvisation of environmental prefigurations, embodying the political imaginaries and power structures that environmental prefigurative politics aspire to realize in society. Third, environmental prefigurative politics also influence the development pathways and situated agency of nature conservation, thereby shaping specific conservation practices. Finally, this study also critiques the environmental prefigurative politics under authoritarian environmentalism, as it also reinforces authoritarian power in subjectivizing individual environmental consciousness.
Background
HPV test-based primary cervical screening is replacing cytology in Canada. In other countries, women's unpreparedness and concerns hindered the transition and post-implementation screening uptake. We investigated psychosocial correlates of intentions of screening in eligible individuals to participate in HPV-based primary cervical screening.
Methods
We conducted a nationwide web-based survey of individuals aged 21–70 years in 2022 and oversampled under-screened individuals. We used five Canadian-validated scales to measure HPV test-based screening knowledge, attitudes, and beliefs. Using the multistage Precaution Adoption Process Model, we assessed women's stage of intentions to participate in HPV testing and self-sampling. We estimated associations of psychosocial factors with intentions' stage using multinomial logistic regression.
Findings
In both groups (adequately screened n = 1778; under-screened n = 1570), higher HPV knowledge was associated with intention for HPV testing and more personal barriers to the HPV test were associated with lower intentions to participate in HPV testing or use of self-sampling. In both groups, higher self-sampling concerns were associated with lower intentions for self-sampling and higher women's need for autonomy was associated with increased intentions for self-sampling. In the under-screened group, increased age was associated with lower intentions for HPV testing and self-sampling, while living in Canada for <10 years was associated with higher intentions.
Interpretation
Our results could be used by policymakers and healthcare professionals to design communication strategies and ensure a smooth transition to HPV-based primary cervical screening, especially for under-screened individuals.
Funding
10.13039/501100000024Canadian Institutes of Health Research project grant 165905.
This study presents the process of design and development of a low-cost turbidimeter for monitoring water quality, facilitating rigorous spatial–temporal variability analysis within large-scale hydrological systems. We propose a low-cost optical turbidimeter, modifying the existent SEN0189 turbidity sensor, Arduino boards, and additional sensors for temperature compensation. We compared a low-cost system with high-tech sensors, modifying the original low-cost SEN0189 probe for enhanced environmental performance. The three-step methodological framework involved prototype development, compensation for environmental factors, and preparation for future field deployment. Calibration equations with a high coefficient of determination and a temperature correction equation were established. We made adaptations to overcome field deployment challenges, including a 3-D printed sensor case, defining the relationship between measurement uncertainty and energy consumption, and specifying field installation guidelines. In summary, this study presents a comprehensive approach to a low-cost optical turbidity system, demonstrating its potential for accurate and affordable field deployment. We aim to address the critical need for sustainable inland water management tools, making this system a valuable contribution to environmental monitoring practices. We also aim to inspire similar development of open-source monitoring systems within our community.
Theorists have argued that objectification is implicated in men’s violence against women. Growing correlational and experimental evidence supports this claim. However, little research has studied the link between objectification and violence perpetrated by intimate partners. Three studies examined this link in relation to several forms of violent behavior. Study 1 (N = 215) found that men who implicitly associated women with objects were more likely to perpetrate sexual and physical violence against their female romantic partner, independent of their levels of hostile sexism. Study 2 (N = 325) replicated this finding but examined automatic associations with men’s intimate partners rather than women as a class. Greater implicit objectification was again associated with self-reported physical violence and with a behavioral proxy measure of aggression among participants who responded most strongly to an experimental provocation. Study 3 (N = 192) manipulated objectification by inducing a physical appearance-focus mindset and found that the manipulation increased men’s tendency to respond violently toward their partner. By implication, objectification appears to play a significant role in facilitating men’s violence in romantic relationships.
Nonstationary Rainfall frequency analysis (RFA) is used to assess how climate change is impacting the likelihood of extreme storms. A key limitation of covariate‐based approaches to nonstationary RFA is that without a physical basis, models selected based on the quality of fit to historical data cannot be reliably projected to estimate future quantiles. Here we propose to improve the physical representation of rainfall processes by using a peaks‐over‐threshold approach to separate the processes of storm intensity (impacted by thermodynamic drivers related to changes in atmospheric moisture) and storm arrival frequency (impacted by dynamic drivers that lead to changes in regional weather systems). Through stochastic experiments we demonstrate that quantiles can only be accurately projected beyond the observed climate when nonstationary models reflect the underlying nonstationary process. Through a case study we demonstrate how climate model projections of rainfall can be utilized to deduce nonstationary model structures, showing that changes in both the storm intensity and storm arrival frequency are needed to accurately estimate future quantiles. While here we propose a single simple physically informed approach for storm intensity, structuring the arrival frequency component requires a detailed understanding of atmospheric dynamics in the region of interest.
Background
Over the past decade, the adoption of screening programs, digital mammography, and magnetic resonance imaging (MRI) has increased early-stage breast cancer diagnosis rates. Mortality rates have decreased due to early detection and improved treatments, including personalized therapies. Accelerated partial-breast irradiation (APBI) is emerging as a convenient and effective treatment for some patients, with studies exploring its preoperative use. Preoperative APBI, especially with MRI guidance, offers improved tumor targeting and potentially reduced side effects. Magnetic Resonance Imaging-Guided Single-Fraction Pre-Operative Radiotherapy for Early-Stage Breast Cancer (RICE trial) aims to assess the feasibility and efficacy of MRI-guided single-dose radiotherapy (RT) for early-stage breast cancer.
Methods
The RICE study is a prospective, single-arm study evaluating single-fraction preoperative, APBI treatment for patients with early-stage breast cancer using a magnetic resonance imaging linear accelerator (MRI linac). Eligible patients enrolled in this study will have a core biopsy to confirm estrogen receptor-positive and HER2-negative sub-type. RT planning will use a planning computed tomography (CT) co-registered with a MRI with the patient in either the supine or prone position. For the diagnostic workup, [18F] fluorodeoxyglucose positron emission tomography/CT ([18F] FDG PET/CT) and [18F] fluoroestradiol positron emission tomography/CT ([18F] FES PET/CT) will be performed prior to treatment. Thirty patients will receive a single ablative RT dose of 21 Gray to the tumor. Pre-treatment and post-treatment MRI scans will be acquired at baseline and 5 weeks post-RT respectively. Breast-conserving surgery will be scheduled for 6 weeks after APBI treatment using the MRI linac.
The primary study endpoint is the successful administration of a single fraction of preoperative breast RT under the guidance of an MRI linac. Secondary endpoints include evaluating the utility of MRI, [18F] FDG PET/CT, and [18F] FES PET/CT as a non-invasive method for assessing treatment response in patients undergoing single-fraction preoperative APBI.
Conclusion
The RICE trial represents a significant step in breast cancer treatment, offering insights that could lead to treatment protocols with minimized RT appointments and enhanced patient outcomes.
Trial registration
This trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR). Registered 31st of May 2021. Registration number: ACTRN12621000659808.
Objective
We aimed to describe the incidence, pathogens, and antimicrobial susceptibility of central line-associated bloodstream infections (CLABSI) in adult intensive care units (ICU).
Design
State surveillance data from 2011 to 2022 were analyzed to identify patient and device days and CLABSI events. Pathogen data were analyzed to determine the most common organisms and patterns of antimicrobial resistance grouped into 3-year time epochs.
Setting
Adult ICU in Victoria, Australia.
Participants
Healthcare organizations participating in CLABSI state surveillance.
Results
608 events were reported over 751,350 device days. Overall, CLABSI incidence was 0.81 per 1,000 central-line days, with a 49.3% rate reduction from 2011 to 2022 (1.39 to 0.70 per 1,000 central-line days). Overall device utilization ratio was 0.57, with a 15.4% reduction from 2011 to 2022 (0.67 vs 0.56). Of 690 pathogens, the most common by rank order were coagulase-negative Staphylococci (CNS), Candida species, Staphylococcus aureus , and Enterococcus faecalis . The proportion of CNS-causing events increased by 69.0% from 2011 to 2022; this trend was not observed for other organisms. For every increase in epoch, a 33% decrease in methicillin-resistant S. aureus (MRSA), 4% increase in vancomycin-resistant Enterococcus faecium , and 12% increase in ceftriaxone-resistant Escherichia coli pathogens were observed.
Conclusions
We demonstrate a decreasing incidence of CLABSI in Victorian adult ICU and an increasing burden of infections due to CNS. No significant time trend increases in antimicrobial-resistant organisms, including MRSA, vancomycin-resistant E. faecium , and ceftriaxone-resistant E. coli were observed. These findings are relevant for identifying priorities for CLABSI prevention in Victorian adult ICU.
Objective: This study examined acute effects of interrupting prolonged sitting with short activity breaks on postprandial glucose/insulin responses and estimations of insulin sensitivity in adults with type 1 diabetes (T1D). Method: In a randomized crossover trial, eight adults (age = 46 ± 14 years [mean ± SD], body mass index [BMI] = 27.2 ± 3.8 kg/m2) receiving continuous subcutaneous insulin infusion (CSII) therapy completed two 6-h conditions as follows: uninterrupted sitting (SIT) and sitting interrupted with 3-min bouts of simple resistance activities (SRAs) every 30 min. Basal and bolus insulin were standardized across conditions except in cases of hypoglycemia. Postprandial responses were assessed using incremental area-under-the-curve (iAUC) and total AUC (tAUC) from half-hourly venous sampling. Meal-based insulin sensitivity determined from glucose sensor and insulin pump (SiSP) was assessed from flash continuous glucose monitor and insulin pump data. Outcomes were analyzed using mixed models adjusted for sex, BMI, treatment order, and preprandial values. Results: Glucose iAUC did not differ by condition (SIT: 19.8 ± 3.0 [estimated marginal means ± standard error] vs. SRA: 14.4 ± 3.0 mmol.6 h.L-1; P = 0.086). Despite CSII being standardized between conditions, insulin iAUC was higher in SRA compared to SIT (137.1 ± 22.7 vs. 170.9 ± 22.7 mU.6 h.L-1; P < 0.001). This resulted in a lower glucose response relative to the change in plasma insulin in SRA (tAUCglu/tAUCins: 0.32 ± 0.02 vs. 0.40 ± 0.02 mmol.mU-1; P = 0.03). SiSP was also higher at dinner following the SRA condition, with no between-condition differences at breakfast or lunch. Conclusion: Regularly interrupting prolonged sitting in T1D may increase plasma insulin and improve insulin sensitivity when meals and CSII are standardized. Future studies should explore underlying mechanistic determinants and the applicability of findings to those on multiple daily injections. Trial Registration: Australian and New Zealand Clinical Trial Registry Identifier-ACTRN12618000126213 (www.anzctr.org.au).
Background:
Nurse staffing levels are increasingly challenged while pressures on healthcare systems are rising. There is a clear need to optimise efficiency in healthcare delivery in order to deliver safe, effective and quality health care.
Aim:
To understand how nurses working shifts spend their time and explore opportunities to improve efficiency in care delivery.
Method:
A time-motion study was conducted on three acute care wards in a district general hospital in West Wales; 13 nurses were observed over 14 shifts, each activity undertaken was recorded in real time.
Findings:
In all, 109 hours were observed. Approximately half of nurses' time is spent delivering direct patient care, with medications administration taking the majority of time.
Conclusion:
A number of recommendations are made involving processes and workforce modelling with the aim of improving efficiency and safety. Further research would be required to assess the impact of their introduction.
Importance
Monogenic causes of childhood hearing loss are well established, as are polygenic risk contributions to age-related hearing loss. However, an untested possibility is that polygenic risk scores (PRS) also contribute to childhood hearing loss of all severities, alongside environmental and/or monogenic causes.
Objective
To examine the association between a PRS for adult hearing loss and childhood hearing loss phenotypes.
Design, Setting, and Participants
This cross-sectional study used a unique population-based dataset spanning normal hearing to profound loss, combining 2 contemporaneous population cohorts in Australia. This included the Child Health CheckPoint, a national population-based cross-sectional study nested within the Longitudinal Study of Australian Children, and the Victorian Childhood Hearing Longitudinal Databank (VicCHILD), a statewide population-based longitudinal data bank open to every child with congenital hearing loss in Victoria, Australia. The analysis took place from March to August 2023.
Exposures
Genotype data were generated from saliva- or blood-derived DNA using global single-nucleotide variations arrays. Based on genotype data, PRS was computed using published UK Biobank genome-wide association study results for self-reported hearing difficulty in individuals aged 40 to 69 years.
Main Outcomes and Measures
Hearing outcomes were classified by laterality (bilateral, unilateral), severity (mild, moderate, severe or worse) and types (sensorineural, conductive, mixed, auditory neuropathy, atresia). Analyses included multinominal logistic regressions of PRS with hearing outcomes.
Results
Overall, 1488 CheckPoint study children (49.8% boys, aged 11-12 years) and 527 VicCHILD study children (55.2% boys, aged 0-13 years) with hearing and genotype data were included. A 1-SD increment in PRS was associated with higher odds of mild (odds ratio [OR], 1.3; 95% CI, 1.0-1.6), moderate (OR, 5.1; 95% CI, 3.2-8.1), and severe or worse (OR, 5.3; 95% CI, 3.9-7.3) unilateral hearing loss compared with normal hearing. Similarly, the PRS was associated with increased odds of mild, moderate, and severe or worse bilateral hearing loss (per-SD ORs, 3.9-6.6) and all hearing loss types (per-SD ORs, 8.5-10.6).
Conclusions and Relevance
In this cross-sectional study, a PRS initially developed for adult hearing difficulty was associated with wide-ranging childhood hearing loss phenotypes, partly explaining hearing phenotype variations despite shared genetic and environmental factors (eg, preterm birth). Large-scale studies with objectively defined hearing phenotypes are crucial for refining PRS and predicting high-risk children.
This untargeted metabolomics study investigated the synergistic antibacterial activity of polymyxin B and Leu10-teixobactin, a depsipeptide inhibitor of cell wall biosynthesis. Checkerboard microdilution assays revealed a significant synergy against polymyxin-susceptible and -resistant A. baumannii, excluding lipopolysaccharide-deficient variants. Time-kill assays confirmed bactericidal synergy, reducing bacterial burden by approximately 4-6-log10CFU/mL. The combination (2xMIC polymyxin B and 0.5xMIC Leu10-teixobactin) prevented bacterial regrowth after 24 h, indicating sustained efficacy against the emergence of resistant mutants. The analysis of A. baumannii ATCC™ 19606 metabolome demonstrated that the polymyxin B–Leu10-teixobactin combination produced more pronounced perturbation compared to the individual antibiotics across all time points (1, 3 and 6 h). Pathway analysis revealed that lipid metabolism, cell envelope biogenesis, and cellular respiration were predominantly impacted by the combination, and to a lesser extent by polymyxin B monotherapy. Leu10-teixobactin treatment alone had only a minor impact on the metabolome, primarily at the 6 h time point. Peptidoglycan assays confirmed the combination’s concerted deleterious effects on bacterial cell envelope integrity. Electron microscopy further substantiated these findings, revealing pronounced cell envelope damage, membrane blebbing, and vacuole formation. These findings highlight the potential of the polymyxin B–Leu10-teixobactin combination as an effective treatment in preventing resistance in A. baumannii.
Purpose
Informal caregivers play a pivotal role in providing support to cancer survivors, yet have reported challenges with communicating with health providers to get all the information they need to provide optimal care. We aimed to adapt and pilot test a brief communication skills training program (COMFORT) to improve caregiver-provider communication in an Australian cancer setting.
Methods
Module adaptation was guided by the cultural adaptation model. A working group completed the module and provided feedback for adaptation. The adapted module underwent pilot testing with cancer caregivers to examine module impact on communication confidence, preparedness for caregiving, health literacy, and psychological outcomes. Semi-structured interviews and survey data provided evidence of acceptability, usability, and preliminary efficacy.
Results
Eight working group members provided mostly positive feedback on module language, content, and images. Module modifications reflected Australian services and terminology. Nineteen caregivers provided pre-post-pilot data and participated in semi-structured interviews. Following module exposure, repeated measures t-test analyses showed significant improvements in communication confidence, preparedness for caregiving, health literacy, and depressive symptoms (p < 0.05). Survey and interview data supported the acceptability and utility of the program.
Conclusion
The findings support the feasibility and preliminary efficacy of the brief module in improving communication confidence, caregiving preparedness, health literacy, and depressive symptoms in Australian cancer caregivers.
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