Prevalence and associations of provision of nursing home visits and home visits by early-career specialist general practitioners.

OBJECTIVE: To establish prevalence and associations of provision of nursing home visits (NHV) and home visits (HV) by early-career specialist GPs. Of particular interest were associations of rurality with performing NHVs and HVs. METHODS: A cross-sectional study. DESIGN: A questionnaire-based study. SETTING: Australian general practice. PARTICIPANTS: Early-career specialist GPs, practising in Australia, who attained Fellowship between January 2016 and July 2018, inclusive, having completed GP training in NSW, the ACT, Eastern Victoria or Tasmania. MAIN OUTCOME MEASURES: Current provision of NHV and HV. RESULTS: NHV were provided by 34% of participants (59% in rural areas) and HV by 41% of participants (60% in rural areas). Remote, rural or regional practice location, as compared to major-city practice, was strongly associated with performing NHV as an early-career specialist GP; multivariable OR 5.87 (95% CI: 2.73, 12.6), p < 0.001, and with the provision of HV; multivariable OR 3.64 (95% CI: 1.63, 8.11), p = 0.002. Rurality of GP training (prior to attaining Fellowship) was significantly univariably associated with providing NHV and with providing HV as an early-career specialist GP. On multivariable analyses, these were no longer statistically significant. CONCLUSION: Early-career specialist GPs located in regional/remote areas are more likely than their urban colleagues to provide NHV and HV.

Perceptions of the effectiveness of using patient encounter data as an education and reflection tool in general practice training.

Introduction Patient encounter tools provide feedback and potentially reflection on general practitioner (GP) registrars' in-practice learning and may contribute to the formative assessment of clinical competencies. However, little is known about the perceived utility of such tools. Aim To investigate the perceived utility of a patient encounter tool by GP registrars, their supervisors, and medical educators (MEs). Methods General practice registrars, supervisors and MEs from two Australian regional training organisations completed a cross-sectional questionnaire. Registrars rated how Registrar Clinical Encounters in Training (ReCEnT), a patient encounter tool, influenced their reflection on, and change in, clinical practice, learning and training. Supervisors' and MEs' perceptions provided contextual information about understanding their registrars' clinical practice, learning and training needs. Results Questionnaires were completed by 48% of registrars (n = 90), 22% of supervisors (n = 182), and 61% of MEs (n = 62). Most registrars agreed that ReCEnT helped them reflect on their clinical practice (79%), learning needs (69%) and training needs (72%). Many registrars reported changing their clinical practice (54%) and learning approaches (51%). Fewer (37%) agreed that ReCEnT influenced them to change their training plans. Most supervisors (68%) and MEs (82%) agreed ReCEnT reports helped them better understand their registrars' clinical practice. Similarly, most supervisors (63%) and MEs (68%) agreed ReCEnT reports helped them better understand their registrars' learning and training needs. Discussion ReCEnT can prompt self-reflection among registrars, leading to changes in clinical practice, learning approaches and training plans. Reaching its potential as an assessment for learning (as opposed to an assessment of learning) requires effective engagement between registrars, their supervisors and MEs.

Exploring how a patient encounter tracking and learning tool is used within general practice training: a qualitative study.

Introduction In Australian general practitioner (GP) training, feedback and reflection on in-practice experience is central to developing GP registrars' (trainees') clinical competencies. Patient encounter tracking and learning tools (PETALs) that encompass an audit of consecutive patient consultations, feedback, and reflection are used to determine registrars' in-practice exposure and have been suggested as a tool for learning within a programmatic assessment framework. However, there is limited qualitative literature on the utility of PETALs in GP training. Aim To provide greater understanding of how PETALs are used in GP training, using Registrars' Clinical Encounters in Training (ReCEnT) as a case study. Methods Medical educators, supervisors, and registrars from two Australian regional GP training organisations participated in focus groups and interviews, designed to explore participants' perceptions of ReCEnT's utility. Data were analysed using reflexive thematic analysis. Results Eight themes were identified that enhance our understanding of: how ReCEnT reports are used (reassuring registrars, facilitating self-reflection, identifying learning needs), what enables ReCEnT to reach its full potential (a culture of reflection, meaningful discussions with supervisors and medical educators, valuing objective data), and differences in understanding about ReCEnT's role in a programmatic assessment framework (as a tool for learning, as 'one piece of the puzzle'). Discussion The findings were used to develop a Structure-Process-Outcomes model to demonstrate how ReCEnT is currently used and explores how it can be used for learning, rather than of learning, in a programmatic assessment framework for GP training. ReCEnT's longitudinal format has potential for enhancing learning throughout training.

General practice registrars training part-time: a cross-sectional analysis of prevalence and associations.

While GPs are working fewer clinical hours and many GP trainees (registrars) do not foresee themselves working full-time in clinical practice, little is known of the epidemiology of registrars training part-time. We aimed to establish the prevalence of general practice part-time training (PTT), and part-time registrars' characteristics and practice patterns. A cross-sectional analysis was conducted of data from the Registrar Clinical Encounters in Training project, an ongoing cohort study of Australian GP registrars' clinical experiences over 60 consecutive consultations in each of three training terms. Univariable and multivariable logistic regression analyses were conducted with the outcome 'training part-time'. 1790 registrars contributed data for 4,135 registrar-terms and 241,945 clinical encounters. Nine hundred and twenty-two registrar-terms (22%, 95%CI:21%-24%) and 52,339 clinical encounters (22%, 95%CI:21%-22%) involved PTT. Factors associated with PTT were registrar characteristics - female gender, older age, in a later training stage, performing other regular medical work; practice characteristics - working in a higher socioeconomic status area; and patient characteristics - seeing more patients new to the registrar and seeing more patients from a non-English-speaking background. No consultation or consultation action factors were significantly associated with PTT. Registrars, practices, and patient associations have GP training implications. The lack of registrar consultation or consultation action associations suggests there may be limited impact of PTT on patient care.

The prevalence and associations of Australian early-career general practitioners' provision of after-hours care.

INTRODUCTION: Access to after-hours care (AHC) is an important aspect of general practice service provision. OBJECTIVE: To establish the prevalence and associations of early-career GPs' provision of AHC. DESIGN: An analysis of data from the New alumni Experiences of Training and independent Unsupervised Practice (NEXT-UP) cross-sectional questionnaire-based study. Participants were early-career GPs (6-month to 2-year post-Fellowship) following the completion of GP vocational training in NSW, the ACT, Victoria or Tasmania. The outcome factor was 'current provision of after-hours care'. Associations of the outcome were established using multivariable logistic regression. FINDINGS: Three hundred and fifty-four early-career GPs participated (response rate 28%). Of these, 322 had responses available for analysis of currently performing AHC. Of these observations, 128 (40%) reported current provision of AHC (55% of rural participants and 32% of urban participants). On multivariable analysis, participants who provided any AHC during training were more likely to be providing AHC (odds ratio (OR) 5.51, [95% confidence interval (CI) 2.80-10.80], p < 0.001). Current rural location and in-training rural experience were strongly associated with currently providing AHC in univariable but not multivariable analysis. DISCUSSION: Early-career GPs who provided AHC during training, compared with those who did not, were more than five times more likely to provide after-hours care in their first 2 years after gaining Fellowship, suggesting participation in AHC during training may have a role in preparing registrars to provide AHC as independent practitioners. CONCLUSION: These findings may inform future GP vocational training policy and practice concerning registrars' provision of AHC during training.

Putting hornets on the genomic map.

Hornets are the largest of the social wasps, and are important regulators of insect populations in their native ranges. Hornets are also very successful as invasive species, with often devastating economic, ecological and societal effects. Understanding why these wasps are such successful invaders is critical to managing future introductions and minimising impact on native biodiversity. Critical to the management toolkit is a comprehensive genomic resource for these insects. Here we provide the annotated genomes for two hornets, Vespa crabro and Vespa velutina. We compare their genomes with those of other social Hymenoptera, including the northern giant hornet Vespa mandarinia. The three hornet genomes show evidence of selection pressure on genes associated with reproduction, which might facilitate the transition into invasive ranges. Vespa crabro has experienced positive selection on the highest number of genes, including those putatively associated with molecular binding and olfactory systems. Caste-specific brain transcriptomic analysis also revealed 133 differentially expressed genes, some of which are associated with olfactory functions. This report provides a spring-board for advancing our understanding of the evolution and ecology of hornets, and opens up opportunities for using molecular methods in the future management of both native and invasive populations of these over-looked insects.

Early-career general practitioners' perceptions of the utility of vocational training for subsequent independent practice.

PURPOSE: To evaluate Australian early-career general practitioners' perceptions of the utility of their prior vocational training in preparing them for independent specialist practice. We hypothesised that in-practice teaching would be perceived as more useful than formal education delivered by Regional Training Organisations (RTOs). METHODS AND MATERIALS: A cross-sectional questionnaire-based study of early-career general practitioners (RTO 'alumni'). The outcomes were Likert scale ratings of alumni's perceived impact of RTO education versus in-practice training on their preparedness for independent practice. Ratings were compared using Wilcoxon signed-rank tests. Multivariable linear regression was used to establish alumni characteristics associated with perceptions of utility of in-practice versus RTO-delivered education. RESULTS: Three hundred and fifty-four alumni responded (response rate 28%). In-practice training was rated statistically significantly higher than RTO education for minor procedural skills, teaching skills, professional responsibilities, tolerating clinical uncertainty, and preparing for managing child and adolescent health, aged care, chronic disease, multi-morbidity and mental health. RTO education rated higher than in-practice training for practising evidence-based medicine and Aboriginal and Torres Strait Islander health. For a number of further areas, there was no statistically significant difference in alumni ratings of utility. CONCLUSIONS: In-practice or RTO-led teaching was perceived as more useful for some components of independent practice, whilst for others there was no significant difference. The findings support recognition of the individual educational components of a blended education/training structure.

Social complexity, life-history and lineage influence the molecular basis of castes in vespid wasps.

A key mechanistic hypothesis for the evolution of division of labour in social insects is that a shared set of genes co-opted from a common solitary ancestral ground plan (a genetic toolkit for sociality) regulates caste differentiation across levels of social complexity. Using brain transcriptome data from nine species of vespid wasps, we test for overlap in differentially expressed caste genes and use machine learning models to predict castes using different gene sets. We find evidence of a shared genetic toolkit across species representing different levels of social complexity. We also find evidence of additional fine-scale differences in predictive gene sets, functional enrichment and rates of gene evolution that are related to level of social complexity, lineage and of colony founding. These results suggest that the concept of a shared genetic toolkit for sociality may be too simplistic to fully describe the process of the major transition to sociality.

Cross-sectional analysis of the clinical work hours of early-career general practitioners.

BACKGROUND AND OBJECTIVES: The clinical working hours of early-career general practitioners (GPs) are an important factor in Australian GP workforce planning. This study aimed to establish the prevalence and associations of early-career GPs working full time (nine or more sessions per week) in clinical practice. METHOD: This was a cross-sectional questionnaire-based study of alumni (from six months to two years post-Fellowship) from three regional training organisations. Multivariable logistic regression was used to establish factors associated with alumni working full time. RESULTS: Of 356 currently practising early-career alumni participants, 30% worked full time. Factors associated with working full time included spouse/partner employment and family structure and any examination failure. Factors associated with working less than full time included female gender, being an Australian medical graduate, provision of other medical work and having taken additional leave during training. DISCUSSION: A high proportion of early-career GPs working part time in clinical general practice has implications for workplace planning, as GPs seek workload diversity and flexibility across their career stages.

Response of the East Antarctic Ice Sheet to past and future climate change.

The East Antarctic Ice Sheet contains the vast majority of Earth's glacier ice (about 52 metres sea-level equivalent), but is often viewed as less vulnerable to global warming than the West Antarctic or Greenland ice sheets. However, some regions of the East Antarctic Ice Sheet have lost mass over recent decades, prompting the need to re-evaluate its sensitivity to climate change. Here we review the response of the East Antarctic Ice Sheet to past warm periods, synthesize current observations of change and evaluate future projections. Some marine-based catchments that underwent notable mass loss during past warm periods are losing mass at present but most projections indicate increased accumulation across the East Antarctic Ice Sheet over the twenty-first century, keeping the ice sheet broadly in balance. Beyond 2100, high-emissions scenarios generate increased ice discharge and potentially several metres of sea-level rise within just a few centuries, but substantial mass loss could be averted if the Paris Agreement to limit warming below 2 degrees Celsius is satisfied.

Pleiotropic constraints promote the evolution of cooperation in cellular groups.

The evolution of cooperation in cellular groups is threatened by lineages of cheaters that proliferate at the expense of the group. These cell lineages occur within microbial communities, and multicellular organisms in the form of tumours and cancer. In contrast to an earlier study, here we show how the evolution of pleiotropic genetic architectures-which link the expression of cooperative and private traits-can protect against cheater lineages and allow cooperation to evolve. We develop an age-structured model of cellular groups and show that cooperation breaks down more slowly within groups that tie expression to a private trait than in groups that do not. We then show that this results in group selection for pleiotropy, which strongly promotes cooperation by limiting the emergence of cheater lineages. These results predict that pleiotropy will rapidly evolve, so long as groups persist long enough for cheater lineages to threaten cooperation. Our results hold when pleiotropic links can be undermined by mutations, when pleiotropy is itself costly, and in mixed-genotype groups such as those that occur in microbes. Finally, we consider features of multicellular organisms-a germ line and delayed reproductive maturity-and show that pleiotropy is again predicted to be important for maintaining cooperation. The study of cancer in multicellular organisms provides the best evidence for pleiotropic constraints, where abberant cell proliferation is linked to apoptosis, senescence, and terminal differentiation. Alongside development from a single cell, we propose that the evolution of pleiotropic constraints has been critical for cooperation in many cellular groups.

Evaluation of neural innervation in the human conventional outflow pathway distal to Schlemm's canal.

The distal outflow pathway of the human eye consists of the outer wall of Schlemm's canal, collector channels, and the deep-scleral, mid-scleral and episcleral vessels. It is the last region of transit for aqueous humor before returning to the venous system. While the trabecular meshwork, scleral spur, and inner wall of Schlemm's canal have been extensively analyzed to define their contributions to aqueous outflow, the role of the distal outflow pathway is not completely understood. Collector channels, emanating from Schlemm's canal were previously thought to be passive conduits for aqueous humor. However, recent studies have shown many collector channels contain flap-like appendages which move with changes in pressure. These findings, along with studies demonstrating innervation of episcleral vessels, have led to questions regarding whether other structures in the distal outflow pathway are under neural regulation and how this may influence aqueous humor outflow. This study evaluates the innervation of the outer wall of Schlemm's canal and collector channels, along with the deep-scleral, mid-scleral and episcleral vasculature with microcomputed tomography and 3-dimensional reconstruction, correlative light microscopy, immunohistochemistry, and transmission electron microscopy. Peripheral, autonomic, and sensory nerve fibers were found to be present adjacent to Schlemm's canal outer wall endothelium, collector channel endothelium, and in the different regions of the distal outflow vasculature. Nerves were more commonly identified in regions that contained collector channels when compared to regions without collector channels. These findings regarding the neural anatomy suggest an active neural regulation of aqueous humor outflow throughout the proximal and distal regions of the conventional outflow pathway.

Prevalence and associations of rural practice location in early-career general practitioners in Australia: a cross-sectional analysis.

OBJECTIVES: To: (1) establish the prevalence of urban, regional, rural and remote practice location of early-career general practitioners (GPs); and (2) examine demographic and training-related characteristics associated with working in regional, rural or remote areas post attainment of vocational general practice qualifications. DESIGN: Cross-sectional, questionnaire-based study, combined with contemporaneously collected data from participants' prior vocational training. SETTING: Australian general practice. PARTICIPANTS: Newly vocationally qualified GPs (ie, within 6 months-2 years post fellowship) who had completed vocational training with regional training organisations in New South Wales, Australian Capital Territory, eastern Victoria, and Tasmania between January 2016 and July 2018. PRIMARY OUTCOME MEASURE: Rurality of post-fellowship practice location, as defined by Modified Monash Model (MMM) geographical classifications, based on current practice postcode. Prevalence of regional/rural/remote ('rural') practice was described using frequencies, and associations of rural practice were established using multivariable logistic regression, considering a range of demographic factors and training characteristics as independent variables. RESULTS: A total of 354 participants completed the questionnaire (response rate 28%) with 319 providing information for their current practice location. Of these, 100 (31.4%) reported currently practising in a rural area (MMM2-7). Factors most strongly associated with practising in a rural area included having undertaken vocational GP training in a rural location OR 16.0 (95% CI 6.79 to 37.9); p<0.001; and undertaking schooling in rural area prior to university OR 4.21 (1.98, 8.94); p<0.001. CONCLUSIONS: The findings suggest that vocational training experience may have a role in rural general practice location post fellowship, attenuating the previously demonstrated 'leakage' from the rural practice pipeline.

Socioeconomic disadvantage and the practice location of recently Fellowed Australian GPs: a cross-sectional analysis.

BACKGROUND: Socioeconomic disadvantage and the 'inverse care law' have significant effects on the health and well-being of Australians. Early career GPs can help address the needs of socioeconomically disadvantaged communities by choosing to practice in these locations. This study addressed an evidence gap around GPs post-Fellowship (within 2 years) practice location, and whether practice location is related to postgraduate vocational training. METHODS: This was a cross-sectional questionnaire-based study of recently Fellowed GPs from New South Wales, the Australian Capital Territory, Victoria and Tasmania. Questionnaire items elicited information about participants' current practice, including location. Where consent was provided, participants' questionnaire responses were linked to previously collected vocational GP training data. The outcome factor in analyses was practice location socioeconomic status (SES): the four deciles of greater socioeconomic disadvantage versus locations with a higher SES. SES was classified according to the Socio-Economic Indexes for Areas - Index of Relative Socioeconomic Disadvantage. Multivariable logistic regression was undertaken. RESULTS: Of participants currently working in clinical general practice, 26% were practicing in the four deciles of greater socioeconomic disadvantage. Significant multivariable associations of working in these locations included having trained in a practice located in an area of greater socioeconomic disadvantage (odds ratio (OR) 3.14), and having worked at their current practice during vocational training (OR 2.99). CONCLUSION: Given the association of training and practice location for recently Fellowed GPs, policies focused on training location may help in addressing ongoing workforce issues faced by areas of higher socioeconomic disadvantage.

Provision of other medical work by Australian early-career general practitioners: a cross-sectional study.

Introduction There is a trend towards GPs diversifying their role by working in health areas beyond general practice. However, little is known about whether this trend is apparent among early-career GPs once they make the transition from training to independent practice. Aim To describe the prevalence of and characteristics associated with early-career GPs providing other medical work. Methods A cross-sectional questionnaire-based study of GPs ('alumni') who had fellowed within the past 2 years from three of Australia's nine regional training programs. The outcome factor was provision of medical work in addition to clinical general practice. Associations of independent variables (encompassing alumni demographics, current practice characteristics and vocational training experience) with the outcome were estimated using univariate and multivariable logistic regression. Results Of 339 responding alumni, 111 (33%) undertook other regular medical work. Sixty-five (59%) of these were in medical education. In multivariable analysis, factors associated with providing other medical work were having a spouse/partner not in the workforce (odds ratio (OR) 5.13), having done any training part-time (OR 2.67), providing two or more of home visits, nursing home visits and after-hours care (OR 2.20), working fewer sessions per week (OR 0.74), and currently working in an area of lower socio-economic status (OR 0.84). Having dependent children (OR 0.27), and being female (OR 0.43) were associated with not providing other medical work. Discussion In this study, many early-career GPs are providing other medical work, particularly medical education. Acknowledging this is important to general practice workforce planning and education policy.

Oracles in Decentralized Finance: Attack Costs, Profits and Mitigation Measures.

Decentralized finance (DeFi) is by far the most popular application of blockchain technology. Despite the wide acceptance of new financial instruments and services, there are still many unexplored areas in the field. We dedicate this research to the understanding of one of the most crucial limitations of decentralized finance-oracles. DeFi protocols, as well as other blockchain applications, function in a closed environment and regularly need to fetch real-world information (e.g., assets' prices)-the tool used for this purpose is called an oracle. We review the existing oracle types in DeFi applications and focus our research on the least explored one: when another protocol, typically a decentralized exchange, serves as a price oracle. After explaining the mechanisms behind the decentralized exchanges, we introduce an algorithmic model that allows one to safely design a decentralized oracle and adjust crucial parameters. We believe that understanding and implementing the logic presented in the model can help to reduce the chances of price manipulations attacks, which are the most frequent incident types in DeFi.

Study protocol: content and perceived educational utility of different modalities of clinical teaching visit (CTV) workplace-based assessments within Australian general practice vocational training: a cross-sectional study.

INTRODUCTION: Clinical teaching visits (CTVs) are formative workplace-based assessments that involve a senior general practitioner (GP) observing a clinical practice session of a general practice registrar (specialist vocational GP trainee). These visits constitute a key part of Australian GP training. Despite being mandatory and resource-intensive, there is a paucity of evidence regarding the content and educational utility of CTVs. This study aims to establish the content and educational utility of CTVs across varying practice settings within Australia, as perceived by registrars and their assessors ('CT visitors'). In addition, this study aims to establish registrar, CT visitor and practice factors associated with CTV content and perceived CTV utility ratings. METHODS AND ANALYSIS: This study will collect data prospectively using online questionnaires completed soon after incident CTVs. Participants will be registrars and CT visitors of CTVs conducted from March 2020 to January 2021. The setting is three Regional Training Organisations across four Australian states and territories (encompassing 37% of Australian GP registrars).Outcome factors will be a number of specified CTV content elements occurring during the CTV as well as participants' perceptions of CTV utility, which will be analysed using univariate and multivariable regression. ETHICS AND DISSEMINATION: Ethics approval has been granted by the University of Newcastle Human Research Ethics Committee, approval number H-2020-0037. Study findings are planned to be disseminated via conference presentation, peer-reviewed journals, educational practice translational workshops and the GP Synergy research subwebsite.

CAR T cells targeting tumor endothelial marker CLEC14A inhibit tumor growth.

Engineering T cells to express chimeric antigen receptors (CARs) specific for antigens on hematological cancers has yielded remarkable clinical responses, but with solid tumors, benefit has been more limited. This may reflect lack of suitable target antigens, immune evasion mechanisms in malignant cells, and/or lack of T cell infiltration into tumors. An alternative approach, to circumvent these problems, is targeting the tumor vasculature rather than the malignant cells directly. CLEC14A is a glycoprotein selectively overexpressed on the vasculature of many solid human cancers and is, therefore, of considerable interest as a target antigen. Here, we generated CARs from 2 CLEC14A-specific antibodies and expressed them in T cells. In vitro studies demonstrated that, when exposed to their target antigen, these engineered T cells proliferate, release IFN-γ, and mediate cytotoxicity. Infusing CAR engineered T cells into healthy mice showed no signs of toxicity, yet these T cells targeted tumor tissue and significantly inhibited tumor growth in 3 mouse models of cancer (Rip-Tag2, mPDAC, and Lewis lung carcinoma). Reduced tumor burden also correlated with significant loss of CLEC14A expression and reduced vascular density within malignant tissues. These data suggest the tumor vasculature can be safely and effectively targeted with CLEC14A-specific CAR T cells, offering a potent and widely applicable therapy for cancer.