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Abstract Introduction Medical education, especially in ultrasound training, is undergoing significant changes. This study examines practical issues in ultrasound medical education, emphasizing state-of-the-art teaching methods, their effectiveness, and implementation challenges. Methods The study analyzed advancements in ultrasound education, including randomized controlled trials comparing peer-to-peer teaching with traditional faculty-led instruction. It evaluated the effectiveness of collaborative small-group training and group size impact in simulation-based training. The study also assessed practical training components outlined in the WFUMB Position Paper Part II. Results Findings indicate that peer-to-peer and collaborative small-group training are effective and cost-efficient. Group size did not significantly affect training outcomes. Key practical training elements, including early hands-on sessions and exposure to various equipment, substantially improved learning outcomes. Simulation tools like virtual reality (VR), augmented reality (AR), and phantoms were crucial for teaching standardized procedures and rare pathologies. Challenges identified include developing robust image acquisition skills, scarcity of qualified student tutors, and the need for reliable ultrasound skill assessment methods. Conclusion Integrating peer-to-peer teaching and advanced simulation technologies significantly advances ultrasound medical education. These methods enhance cognitive and psychomotor skills but also present challenges such as ensuring quality education and developing effective assessment methods. Future research should compare different simulation tools and establish objective ultrasound proficiency assessment criteria. Continual method evaluation and improvement are essential for effective and standardized ultrasound training, ultimately enhancing patient care and clinical outcomes.

Abstract Background Anti-angiogenic, VEGF inhibitors (VEGFi) increase progression-free survival (PFS) and, in some cases, overall survival in many solid tumours. However, their use has been compromised by a lack of informative biomarkers. We have shown that plasma Tie2 is the first tumour vascular response biomarker for VEGFi in ovarian, colorectal and gall bladder cancer: If plasma Tie2 concentrations do not change after 9 weeks of treatment with a VEGFi, the patient does not benefit, whereas a confirmed reduction of at least 10% plasma Tie2 defines a vascular response with a hazard ratio (HR) for PFS of 0.56. The aim of the VALTIVE1 study is to validate the utility of plasma Tie2 as a vascular response biomarker and to optimise the Tie2-definition of vascular response so that the subsequent randomised discontinuation VALTIVE2 study can be powered optimally. Methods VALTIVE1 is a multi-centre, single arm, non-interventional biomarker study, with a sample size of 205 participants (176 bevacizumab-treated participants + 29 participants receiving bevacizumab and olaparib/PARPi), who are 16 years or older, have FIGO stage IIIc/IV ovarian cancer on treatment with first-line platinum-based chemotherapy and bevacizumab. Their blood plasma samples will be collected before, during, and after treatment and the concentration of Tie2 will be determined. The primary objective is to define the PFS difference between Tie2-defined vascular responders and Tie2-defined vascular non-responders in patients receiving bevacizumab for high-risk Ovarian Cancer. Secondary objectives include defining the relationship between Tie2-defined vascular progression and disease progression assessed according to RECIST 1.1 criteria and assessing the impact of PARPi on the plasma concentration of Tie2 and, therefore, the decision-making utility of Tie2 as a vascular response biomarker for bevacizumab during combined bevacizumab-PARPi maintenance. Discussion There is an urgent need to establish a test that tells patients and their doctors when VEGFi are working and when they stop working. The data generated from this study will be used to design a second trial aiming to prove conclusively the value of the Tie2 test. Trial registration ClinicalTrials.gov identifier: NCT04523116. Registered on 21 Aug 2020.

The metallome has been involved in the pathological investigation into ocular tissue for decades; however, as technologies advance, more information can be ascertained from individual tissue sections that were not previously possible. Herein, a demonstration of complementary techniques has been utilized to describe the distribution and concentrations of essential metals in both wildtype (WT) and rhodopsin (Rho−/−) ocular tissues. The multimodal approach described is an example of complementary datasets that can be produced when employing a multifaceted analytical approach. Heterogenous distributions of copper and zinc were observable within both WT and Rho−/− tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), and the distributions of further trace elements notoriously problematic for ICP-MS analysis (phosphorous, Sulfur, chlorine, potassium, calcium, iron, and aluminum) were analysed by particle-induced X-ray emission (PIXE).

Australia has multiple lagoviruses with differing pathogenicity. The circulation of these viruses was traditionally determined through opportunistic sampling events. In the lead up to the nationwide release of RHDVa-K5 (GI.1aP-GI.1a) in 2017, an existing citizen science program, RabbitScan, was augmented to allow members of the public to submit samples collected from dead leporids for lagovirus testing. This study describes the information obtained from the increased number of leporid samples received between 2015 and 2022 and focuses on the recent epidemiological interactions and evolutionary trajectory of circulating lagoviruses in Australia between October 2020 and December 2022. A total of 2771 samples were tested from January 2015 to December 2022, of which 1643 were lagovirus-positive. Notable changes in the distribution of lagovirus variants were observed, predominantly in Western Australia, where RHDV2-4c (GI.4cP-GI.2) was detected again in 2021 after initially being reported to be present in 2018. Interestingly, we found evidence that the deliberately released RHDVa-K5 was able to establish and circulate in wild rabbit populations in WA. Overall, the incorporation of citizen science approaches proved to be a cost-efficient method to increase the sampling area and enable an in-depth analysis of lagovirus distribution, genetic diversity, and interactions. The maintenance of such programs is essential to enable continued investigations of the critical parameters affecting the biocontrol of feral rabbit populations in Australia, as well as to enable the detection of any potential future incursions.

Following the arrival of rabbit haemorrhagic disease virus 2 (RHDV2) in Australia, average rabbit population abundances were reduced by 60% between 2014 and 2018 based on monitoring data acquired from 18 sites across Australia. During this period, as the seropositivity to RHDV2 increased, concurrent decreases were observed in the seroprevalence of both the previously circulating RHDV1 and RCVA, a benign endemic rabbit calicivirus. However, the detection of substantial RHDV1 seropositivity in juvenile rabbits suggested that infections were continuing to occur, ruling out the rapid extinction of this variant. Here we investigate whether the co-circulation of two pathogenic RHDV variants was sustained after 2018 and whether the initially observed impact on rabbit abundance was still maintained. We monitored rabbit abundance and seropositivity to RHDV2, RHDV1 and RCVA at six of the initial eighteen sites until the summer of 2022. We observed sustained suppression of rabbit abundance at five of the six sites, with the average population reduction across all six sites being 64%. Across all sites, average RHDV2 seroprevalence remained high, reaching 60–70% in adult rabbits and 30–40% in juvenile rabbits. In contrast, average RHDV1 seroprevalence declined to

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Focal lesions of the adrenal glands are incidentally detected in approximately 5% of cases by modern imaging techniques. Fewer than 5% of these adrenal incidentalomas are malignant and approximately 10% have endocrine activity. Reliable differentiation of malignant versus benign and hormonally active versus nonfunctional adrenal incidentalomas significantly influences therapeutic management and the outcome of affected individuals. Therefore, each adrenal incidentaloma should undergo a standardized diagnostic work-up to exclude malignancy and endocrine activity. This position statement of the World Federation of Ultrasound in Medicine and Biology (WFUMB) summarizes the available evidence on the management of adrenal incidentaloma and describes efficient management strategies with particular reference to the role of ultrasound techniques.

Managing pest vertebrate species in Australia is a significant challenge for government, industry, research sectors and land-managers. Innovative tools such as genetic biocontrol offers decision-makers a potentially effective means of reducing the impact of pest species incursions. To determine the conditions for investment in genetic biocontrol, we applied qualitative engagement methodologies to identify and integrate existing knowledge of pest species research and management in Australia. Two facilitated workshops were held to determine key topics related to genetic biocontrol technologies for selected pest species. The topics explored during workshop discussions included: identifying existing knowledge gaps; risk perceptions; social and ethical considerations and; industry and business considerations. The workshops' aim was to assess the potential, the priorities and the risk parameters among expert stakeholders and decision-makers for using genetic biocontrol approaches to reduce the impacts of key pest species in Australia. This paper reports on the design, process and outcomes of each workshop to inform the creation of a decision framework. Stakeholders were cautiously optimistic of pursuing continued research and development for vertebrate pest management in Australia. However, employing an appropriate, transparent process for incorporating diverse stakeholder perspectives on genetic biocontrol technologies is essential to ensure their development and use remains supported. This outcome will require meaningful investment in both social science investigations and well-considered engagement processes concurrent with biotechnology development globally.

Determining the locations of proteins within the eye thought to be involved in ocular pathogenesis is important to determine how best to target them for therapeutic benefits. However, immunohistochemistry is limited by the availability and specificity of antibodies. Additionally, the perceived role of both essential and non-essential metals within ocular tissue has been at the forefront of age-related macular degeneration (AMD) pathology for decades, yet even key metals such as copper and zinc have yet to have their roles deconvoluted. Here, mass spectrometry imaging (MSI) is employed to identify and spatially characterize both proteomic and metallomic species within ocular tissue to advance the application of a multiomic imaging methodology for the investigation of ocular diseases.

Host immune activation forms a vital line of defence against bacterial pathogenicity. However, just as hosts have evolved immune responses, bacteria have developed means to escape, hijack and subvert these responses to promote survival. In recent years, a highly conserved group of signalling cascades within the host, collectively termed the integrated stress response (ISR), have become increasingly implicated in immune activation during bacterial infection. Activation of the ISR leads to a complex web of cellular reprogramming, which ultimately results in the paradoxical outcomes of either cellular homeostasis or cell death. Therefore, any pathogen with means to manipulate this pathway could induce a range of cellular outcomes and benefit from favourable conditions for long-term survival and replication. This review aims to outline what is currently known about bacterial manipulation of the ISR and present key hypotheses highlighting areas for future research.

Public perceptions of pandemic viral threats and government policies can influence adherence to containment, delay, and mitigation policies such as physical distancing, hygienic practices, use of physical barriers, uptake of testing, contact tracing, and vaccination programs. The UK COVID-19 Public Experiences (COPE) study aims to identify determinants of health behaviour using the Capability, Opportunity, Motivation (COM-B) model using a longitudinal mixed-methods approach. Here, we provide a detailed description of the demographic and self-reported health characteristics of the COPE cohort at baseline assessment, an overview of data collected, and plans for follow-up of the cohort. The COPE baseline survey was completed by 11,113 UK adult residents (18+ years of age). Baseline data collection started on the 13th of March 2020 (10-days before the introduction of the first national COVID-19 lockdown in the UK) and finished on the 13th of April 2020. Participants were recruited via the HealthWise Wales (HWW) research registry and through social media snowballing and advertising (Facebook®, Twitter®, Instagram®). Participants were predominantly female (69%), over 50 years of age (68%), identified as white (98%), and were living with their partner (68%). A large proportion (67%) had a college/university level education, and half reported a pre-existing health condition (50%). Initial follow-up plans for the cohort included in-depth surveys at 3-months and 12-months after the first UK national lockdown to assess short and medium-term effects of the pandemic on health behaviour and subjective health and well-being. Additional consent will be sought from participants at follow-up for data linkage and surveys at 18 and 24-months after the initial UK national lockdown. A large non-random sample was recruited to the COPE cohort during the early stages of the COVID-19 pandemic, which will enable longitudinal analysis of the determinants of health behaviour and changes in subjective health and well-being over the course of the pandemic.

The 2017 survey of Faculty Attitude on Technology conducted by Insider Higher Ed reported on the low percentage of partnerships between university faculty and instructional designers in online course development. Experts said it is not a surprise because instructional designers are underutilized and their role in Higher Education is still not clear. This qualitative study examined the faculty members’ perceptions about their mentorship relations with instructional designers when they designed and developed asynchronous online courses. This study also explored factors that may lead to successful mentorship relationships between instructional designers as mentors and faculty members as mentees. Higher education administration, university faculty, and instructional designers will benefit from the results of this study.

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21276-3

Invasive animals have been linked to the extinctions of native wildlife, and to significant agricultural financial losses or impacts. Current approaches to control invasive species require ongoing resources and management over large geographic scales, and often result in the short-term suppression of populations. New and innovative approaches are warranted. Recently, the RNA guided gene drive system based on CRISPR/Cas9 is being proposed as a potential gene editing tool that could be used by wildlife managers as a non-lethal addition or alternative to help reduce pest animal populations. While regulatory control and social acceptance are crucial issues that must be addressed, there is an opportunity now to identify the knowledge and research gaps that exist for some important invasive species. Here we systematically determine the knowledge gaps for pest species for which gene drives could potentially be applied. We apply a conceptual ecological risk framework within the gene drive context within an Australian environment to identify key requirements for undertaking work on seven exemplar invasive species in Australia. This framework allows an evaluation of the potential research on an invasive species of interest and within a gene drive and risk context. We consider the currently available biological, genetic and ecological information for the house mouse, European red fox, feral cat, European rabbit, cane toad, black rat and European starling to evaluate knowledge gaps and identify candidate species for future research. We discuss these findings in the context of future thematic areas of research worth pursuing in preparation for a more formal assessment of the use of gene drives as a novel strategy for the control of these and other invasive species. Keywords: Invasive species, Gene drive, CRISPR, Pest management, Islands

Biological invasions are not only a major threat to biodiversity, they also have major impacts on local economies and agricultural production systems. Once established, the connection of local populations into metapopulation networks facilitates dispersal at landscape scales, generating spatial dynamics that can impact the outcome of pest-management actions. Much planning goes into landscape-scale invasive species management. However, effective management requires knowledge on the interplay between metapopulation network topology and management actions. We address this knowledge gap using simulation models to explore the effectiveness of two common management strategies, applied across different extents and according to different rules for selecting target localities in metapopulations with different network topologies. These management actions are: (i) general population reduction, and (ii) reduction of an obligate resource. The reduction of an obligate resource was generally more efficient than population reduction for depleting populations at landscape scales. However, the way in which local populations are selected for management is important when the topology of the metapopulation is heterogeneous in terms of the distribution of connections among local populations. We tested these broad findings using real-world scenarios of European rabbits (Oryctolagus cuniculus) infesting agricultural landscapes in Western Australia. Although management strategies targeting central populations were more effective in simulated heterogeneous metapopulation structures, no difference was observed in real-world metapopulation structures that are highly homogeneous. In large metapopulations with high proximity and connectivity of neighbouring populations, different spatial management strategies yield similar outcomes. Directly considering spatial attributes in pest-management actions will be most important for metapopulation networks with heterogeneously distributed links. Our modelling framework provides a simple approach for identifying the best possible management strategy for invasive species based on metapopulation structure and control capacity. This information can be used by managers trying to devise efficient landscape-oriented management strategies for invasive species and can also generate insights for conservation purposes.

Climate change is a critical scientific and social issue of our time, yet the topic is not frequently discussed by the general public. Additionally, misconceptions about the topic persist. One important aspect of climate change is the greenhouse effect. This activity adds a greenhouse gas discussion to an existing module about molecular shape and modeling. The module links the greenhouse effect to climate change. The activity has been used in several introductory chemistry settings. A discussion of student-generated answers and student-reported learning gains is presented.

We tested for interactions between body mass index (BMI) and common genetic variants affecting serum urate levels, genome-wide, in up to 42569 participants. Both stratified genome-wide association (GWAS) analyses, in lean, overweight and obese individuals, and regression-type analyses in a non BMI-stratified overall sample were performed. The former did not uncover any novel locus with a major main effect, but supported modulation of effects for some known and potentially new urate loci. The latter highlighted a SNP at RBFOX3 reaching genome-wide significant level (effect size 0.014, 95% CI 0.008-0.02, Pinter= 2.6 x 10-8). Two top loci in interaction term analyses, RBFOX3 and ERO1LB-EDARADD, also displayed suggestive differences in main effect size between the lean and obese strata. All top ranking loci for urate effect differences between BMI categories were novel and most had small magnitude but opposite direction effects between strata. They include the locus RBMS1-TANK (men, Pdifflean-overweight= 4.7 x 10-8), a region that has been associated with several obesity related traits, and TSPYL5 (men, Pdifflean-overweight= 9.1 x 10-8), regulating adipocytes-produced estradiol. The top-ranking known urate loci was ABCG2, the strongest known gout risk locus, with an effect halved in obese compared to lean men (Pdifflean-obese= 2 x 10-4). Finally, pathway analysis suggested a role for N-glycan biosynthesis as a prominent urate-associated pathway in the lean stratum. These results illustrate a potentially powerful way to monitor changes occurring in obesogenic environment.